Head First: The Complete Guide to Healing and Optimizing Your Brain with Nootropic Supplements - 2Nd Edition 9798765236581, 9798765236543, 9798765236550

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HEAD FIRST The Complete Guide to Healing and Optimizing Your Brain with Nootropic Supplements 2ND EDITION

DAVID TOMEN

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Copyright © 2022 David Tomen. All rights reserved. No part of this book may be used or reproduced by any means, graphic, electronic, or mechanical, including photocopying, recording, taping or by any information storage retrieval system without the written permission of the author except in the case of brief quotations embodied in critical articles and reviews. This book is a work of non-fiction. Unless otherwise noted, the author and the publisher make no explicit guarantees as to the accuracy of the information contained in this book and in some cases, names of people and places have been altered to protect their privacy. Balboa Press A Division of Hay House 1663 Liberty Drive Bloomington, IN 47403 www.balboapress.com 844-682-1282 Because of the dynamic nature of the Internet, any web addresses or links contained in this book may have changed since publication and may no longer be valid. The views expressed in this work are solely those of the author and do not necessarily reflect the views of the publisher, and the publisher hereby disclaims any responsibility for them. The author of this book does not dispense medical advice or prescribe the use of any technique as a form of treatment for physical, emotional, or medical problems without the advice of a physician, either directly or indirectly. The intent of the author is only to offer information of a general nature to help you in your quest for emotional and spiritual well-being. In the event you use any of the information in this book for yourself, which is your constitutional right, the author and the publisher assume no responsibility for your actions. Any people depicted in stock imagery provided by Getty Images are models, and such images are being used for illustrative purposes only. Certain stock imagery © Getty Images. Interior Image Credit: David Tomen ISBN: 979-8-7652-3654-3 (sc) ISBN: 979-8-7652-3655-0 (hc) ISBN: 979-8-7652-3658-1 (e) Library of Congress Control Number: 2022921430 Balboa Press rev. date: 11/22/2022

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CONTENTS Acknowledgements Introduction Top 7 Brain Hacking Principles There is No “Magic Pill” Dosage and Synergy Start Low and Slow Avoid Tolerance Choosing the Right Nootropic Stay Safe Evaluating your Nootropic Stack Your Brain is Part of a System How Your Brain Works Brain Architecture Cognitive Architecture Cerebral Cortex The Gatekeepers Neurons & Synapses Cell Membranes Brain Cell Signaling Neurotransmitters Glutamate GABA Acetylcholine Dopamine Epinephrine & Norepinephrine Serotonin Improve Your Memory with Nootropics Types of Memory List of Nootropics Acetyl-L-Carnitine Alpha GPC Alpha-Lipoic Acid Aniracetam Artichoke Extract (Luteolin) Ashwagandha Bacopa Monnieri

Cat’s Claw Choline Bitartrate Choline Citrate CDP-Choline (Citicoline) Centrophenoxine Coluracetam Coenzyme Q10 (CoQ10) Creatine DHEA DMAE 5-HTP Fisetin Forskolin GABA Ginkgo Biloba Ginseng Gotu Kola Huperzine-A Iodine Kava L-Carnosine L-DOPA Lemon Balm L-Glutamine Lion’s Mane L-Theanine Magnesium Magnolia Bark Medicinal Nootropic Mushrooms Melatonin Methylene Blue N-Acetyl L-Cysteine N-Acetyl L-Tyrosine NADH Nefiracetam Nicotine Noopept Oat Straw Oxiracetam Passionflower Phenibut

Phenylalanine Phenylethylamine (PEA) Phenylpiracetam Phosphatidylcholine (PC) Phosphatidylserine (PS) Picamilon Pine Bark Extract Piperine Piracetam Polygala Tenuifolia PQQ Pramiracetam Pterostilbene Quercetin Resveratrol Rhodiola Rosea Rosemary Saffron SAM-e St. John’s wort Sulbutiamine Sulforaphane Taurine Tryptophan Turmeric Tyrosine Uridine Monophosphate Valerian Vinpocetine Vitamin B1 (Thiamine) Vitamin B3 (Niacin) Vitamin B5 (Pantothenic Acid) Vitamin B6 (Pyridoxine) Vitamin B8 (Inositol) Vitamin B9 (Folate) Vitamin B12 (Cobalamin) Vitamin D Zinc Nootropic Stack Recommendations Best Nootropics for Cognition, Thinking and Decision-Making Best Nootropics for Memory

Best Nootropics for Depression & Anxiety Best Nootropics for Energy (physical & mental) & Motivation Best Nootropics for Brain Repair and Maintenance How to Create the Best Nootropic Stack The Most Effective Nootropic Stack for You Your First Nootropic Stack Nootropics for Cognition, Thinking and Decision-Making Nootropics for Memory Nootropics for Anxiety and Depression Nootropics for Energy and Motivation Nootropics for Brain Repair and Maintenance Conclusion My Nootropic Stack Nootropics Glossary References

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Praise From Experts and Readers of Head First, NootropicsExpert.com, and the Nootropics Expert® YouTube channel Thank you, David Tomen. Great info. Simply amazing. Super organized. ~ R David Young I used to be an anxiety ridden self-deprecating mess. I have you to thank for consolidating all this information in an easily accessible format. You have my eternal thanks. Nootropics gave me the opportunity to reclaim my life. You made this process exponentially easier. I am now perusing a double major in neuroscience and philosophy. You sparked my interest in the study of the brain. You helped me find purpose again. ~ A. Hazelwood Thankyou sir for not only sharing your wisdom but for also being transparent including solutions and personal hacks to your own mental health! ~ K Schiffer You truly are an amazing mentor and it shows in just how much you are improving in yourself. I have taken your advice over these last few years and have seen a dramatic improvement in my health as well and none of it would be possible without your informative and helpful videos. Thank you so much kind sir :). I truly owe my life in a way to you and all that you have given me. ~ Savotarax David’s book Head First is an amazing manual and gift. I could not do this on my own, honestly only a few individuals could. If like most people who are desirous of more mental clarity, better moods, and overall optimal energy - you now have a grounded human being and experienced guide to - get you started, move you along or trim tab your trajectory!” ~ P. Masters Head First is full of useful information about brain supplements. I like the way it is written with a lot of structure and easy to understand, even for non-native English speakers. There is not only explanation about the benefits, but also for the risks and side effects and the writer David Tomen always promotes to stay on the safe side. This helps to choose and use the right supplements for oneself. Thank you so much for writing this book. A “must read” for any medical professional. ~ P. Volkova Thank you for the information you present. I find it not only useful but highly accurate. ~ A. Schinitsky I’m not a comments person, but you deserve a Big Thank You from me. I started taking supplements after listening to your vids. So glad I did. I get so many complements on my appearance and energy now because I feel great... still working in my own business at 70. I love learning about what makes me work better. Please don’t stop. ~ M. Miller Hey David. I’ve seen and been inspired by your stuff for a long time. Seriously good content you’re making! ~ S. Oslu Thank you for putting out such good information. ~ Douglas D. David is always amazing. Great content backed by research and studies. ~ Kiya Thanks David. You’re my number one nootropic reference. I’ve loaded and searched your website thousands of times. ~ Y.Y.

I just went to one of your links and this is the first time I saw a goldmine in print. Great stuff! Thank you. I have to get your books as well. There really is a Santa Claus. ~ J. Kelley I am truly grateful for the information you share and provide. What you give to us carries a tremendous amount of value. David Tomen, you are a huge inspiration to me, and I genuinely appreciate your existence. I’m grateful beyond what I can manage to express through words. ~ S. Gjerde After 20 years of depression and social anxiety, you changed my life, David. My name is David too, and I thank you. ~ D. Dave I love that you understand the nutritive aspects as primary, including the importance of the correct fats. And then you go into the nootropics that might assist you as supplements. Bravo, sir. ~ S. Keefe VERY thorough... an excellent list and very comprehensive explanations... thank you... time to do my homework. Great job David! ~ T. Walz Thank you for great content! I always learn so much! ~ anyaleto I have been so impressed with your videos. I just came upon them by mistake. It’s almost like my angels are speaking to me. Thank you and been so informative. ~ Ellen Just watching your videos help relieve my anxiety... You’re like the Bob Ross of nootropics. Thanks for all you do! My go to guy for nootropics. ~ A. Donaldson God bless you, David Tomen. I’ve gone from a 10 to a 5. I’m not in bed all day. I followed your depression recommendations. Thank you. It still feels impossible to get up in the morning, but I get up. It’s unbelievable. ~ LB Excellent video on the mechanisms involved in anxiety disorders and which supplements help which type! Top notch and easy for me as a novice supplement user to understand. Thanks. ~ J. Hunt Well, David…. Holy glockamorras! All I can say is “there is something different” as to the way both my wife and I feel. I am an “old hack” at all this stuff and perfectly healthy because of it! And my wife as well! I am 64 and she’s 42. But this is OUTSTANDING! Thank you so very, very much from both of us. We will see you on the “other side”, to thank you in person. In Spirit. ~ C & E O’Riada So much good information! This is a good example of how using whole foods or full spectrum extracts often work best as compared to single compounds. I’ve got some organic artichoke extract inbound and I can hardly wait to try it! The recommended stack here seems like something students could really benefit from, so I’ll be sharing this information (and products soon) with my local university population. Thanks for all your diligent and quality work David! I really appreciate the journal sources. ~ Adam THANKS, DAVID, SO VERY MUCH!! I have so many of these issues. I was in a horrible accident. Back in 2000, I had to relearn everything all over again. The surgeries I have gone through has been a living nightmare. I would have killed for this supplement back then when I was struggling so. Thanks again!! ~ C. Magee

David, thanks for your commitment and thorough information. I’ve been my own lab rat for about 2 years now and the rat is doing much better. Your site has been indispensable. ~ Kevin Thank you so much for your valuable work. I am a victim of childhood domestic violence and I diagnosed myself with PTSD after reading psychological literature on trauma. I find that the talking cure does not cure childhood memories of abuse but only prolongs feelings of helplessness and bitterness. The minute I started looking into nootropics, the traumatic memories and preoccupation with the past began to subside. Even when I do feel bitter, the feelings subside and I’m able to redirect my energies to the here and now. Neuroscience truly is the answer to trauma because you can’t fix a physical problem by simply talking about it. It’s like trying to talk your way out of a broken leg. I find your work on nootropics to be so thorough and enjoy your tailormade research and attention to nuance. You are helping create positive change in the world. Thank you. ~ Christina David, thank you for your continuing efforts in service to your fellow man. You are truly demonstrating that you are living the lessons received through meditation! At times we need to realize we need to focus on the solution rather than the problem. Directing our mind and internal resources to the creation of what we desire. Your work demonstrates this principle. Our minds CANNOT; Not think of something: such as NOW seeing the color RED. Our thoughts create our reality. Meditation could be considered a reset mechanism. ~ B. Tegeler Great article on Mitochondria support is terrific! I am 70, still working & want to focus my nootropics on longevity & the Mitochondria. Again a great article from one of the “reliable” voices in the nootropic arena. ~ A. Robinson This Spring you helped me get started with Nootropics through a consultation. Wanted to say thank you and tell you and your followers how well I have progressed. I started with basics like Alpha GPC, Lions Main, L-Tyrosine, Pine Bark, Phenylpiracetam, Tart Cherry, Lemon Bark, and L-Tryptophan. I have since added Rhodiola Rosea, Vinpocetine and Polygala Tenuifolia. After fighting depression for so many years and being lethargic and sleepy, I am a new person because I’m happy, productive, and not taking long naps as I used to. I started off taking Adrafinil but don’t need that any longer. Had tried antidepressants, all SSRIs, with no luck and now I understand why they didn’t work after reading your material and listening to your podcasts and doing some of my own research. Thanks again and good luck to everyone else out there. ~ C. Crawley Dear David, thank you for all the incredibly valuable information!! My mother died just before her 69th birthday – 11 years suffering with Alzheimer’s. The recent info on choline has been priceless for my husband (71) and myself (66)! Within the 1st day of taking one 250 mg capsule Citicoline our lives have changed for the BETTER! We both noticed instant better eyesight with clearer distant viewing, along with the ‘overwhelm’ being replaced with ease in being able to focus, concentrate and Get Things Done (procrastination is out the window!). You are An Angel From Heaven – Thanks from the bottom of our hearts! ~ K & B Tarte Hi David! Thank you, I try to recommend your blog to as many people as I can, over 20 people so far :). I changed my life because of YOU. Thank you for all your wisdom, Sir. ~ Sandra

Just want to thank you for your amazing work! I thought I could analyze! You’re the best on the Internet! Thank you. ~ R. Long I had no idea that important nootropics from turmeric aren’t always absorbed by your body. I will make sure to keep this in mind when I shop for more supplements online later today. I love turmeric, but I want to make sure my body is using it correctly. Thanks so much for your lovely advice and incredible insights. ~ D. McDougal Congratulations for having the BEST site of all time on the internet! Amaaaazing! Thank you, thank you, thank you for so selflessly sharing this with the very many people confused and suffering with strange new symptoms and lack of energy etc. I have now found the Holy Grail of info especially about stacking which was my big worry taking so many pills with each meal and also how to do intermittent fasting or OMAD and still take all my supplements. I look forward to finding all the answers on your site!!! Forever grateful. ~ Amelia Amazingly helpful thank you. Life saver actually. ~ Sam

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ACKNOWLEDGEMENTS For the love of my life, Larah, who has been with me on beach days and hurricanes. And has never stopped showering me with love every single day. Thank you, my love. I love you. For my late father, Paul, who believed in me and continued to support me even when things looked bleak. I feel fortunate to have been raised in a loving home that prepared me for adulthood and a nevergive-up attitude that has served me well. Thank you, Dad. And for Dave Wright who gave me the idea to start Nootropics Expert®. And his continued support while building this business. Thank you, Dave.

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Medical Disclaimer The information in this book is the result of years of research and practical experience by the author. This book is not a substitute for an evaluation or treatment by a competent medical professional or specialist. If you think you need medical help, please see a medical practitioner or doctor as soon as possible. The clinical research in this book is true and based on thousands of peer-reviewed clinical studies. But none of the information provided in this book has been evaluated by the Food and Drug Administration. The products and supplements referred to anywhere in this book, on the Nootropics Expert website, and YouTube channel ae not intended to diagnose, treat, cure, or prevent any disease.

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INTRODUCTION If you’ve spent any time on my website NootropicsExpert.com, or have experimented with nootropics before, you have a good idea how certain nootropic supplements can benefit your brain. But if you’re just getting started with nootropics, the choices can seem overwhelming. Where do you start? Allow me a minute or two to share my story. How I discovered nootropics. And how I ended up with the nootropic stack I’m using now. I met a beautiful blonde girl on North Miami Beach about 18 years ago. Six months later we got married. And we are still married today. Marrying Larah is the best decision I have ever made. But during our first year together she could see the problems I was having with focus and memory. I had been struggling with focus all of my adult life. Every executive job I had resulted in a yearly performance review. “David, you are a fantastic manger, a great executive, good salesmen, and people love working with you. But you have got to learn how to focus.” Every single year. So, I went out and bought the books on how to focus. And how to be a good executive. But I couldn’t get it. I thought it was a moral failing. So, after about a year together, Larah saw what was happening. She told me to see a psychiatrist she knew in Palm Beach, Florida. Turns out this doc was a rock star. In the first 10 minutes he diagnosed me with Adult ADD and PTSD. For Adult ADD I was prescribed Ritalin. And from the very first day using Ritalin it was like someone turned the lights on in my brain. For the first time in my life I could focus. But it didn’t last. After a couple of great years, Ritalin no longer worked as well as it once did. And I panicked. I finally find something that works, and it stops working? I don’t think so. Now, keep in mind there were no books or websites I could go for help. I had to figure this out on my own. So, I started reading clinical studies on how Ritalin works. Ritalin is a dopamine reuptake inhibitor. And if it no longer worked as well maybe that means I don’t have enough dopamine in my brain? How do I fix that? I also discovered that brain cell signaling was a problem in those dealing with ADD and ADHD. And that was dependent on adequate levels of acetylcholine in my brain. How do I increase acetylcholine? Turns out that L-Tyrosine boosts dopamine. And Alpha GPC along with ALCAR increases acetylcholine. So, I went around the corner to a GNC store near us. And bought L-Tyrosine, Alpha GPC

and ALCAR. I took these supplements home and started using them 3-times per day. Ritalin started working again. And I have not increased my Ritalin dose since. Nor do I experience a stimulant crash later in the afternoon as long as I take the same supplements again around 4 PM. Fast forward about 8 years and I started getting really sick. So sick that I could not work. My business was failing, marriage was on the rocks, we were out of money, and I felt like I wanted to die. It got so bad that one day I ended up in the ER. What my wife feared was a heart attack turned out to be hypothyroidism. A non-functioning thyroid came with chronic fatigue syndrome, severe brain fog, memory loss, fibromyalgia, chronic pain, and adrenal fatigue. We endured endless visits to specialists and renowned hospitals including the Cleveland Clinic. Along with episodes of not remembering dates and appointments, a failing business, a crumbling marriage, doctors, endocrinologists, neuroscience specialists and therapists. Two unrelated neurologists tested me for dementia, and early-onset Alzheimer’s disease. One of the tests was the “Mini-Mental State Exam”. The doctor asked a series of questions designed to test a range of everyday mental skills. The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia. I got 30 points on every test which meant I didn’t have dementia. Mini-cog During the mini-cog, a person is asked to complete two tasks: 1. Remember, and a few minutes later, repeat the names of three common objects. 2. Draw a face of a clock showing all 12 numbers in the right places and a time specified by the examiner. The results of this brief test can help a physician determine if further evaluation is needed.1

I’m a writer, and not an artist. But was able to draw a near perfect clock. So it was becoming increasingly clear that this was not dementia, or Alzheimer’s. But clearly my brain was not working nearly as well as it should. The medical bills kept stacking up, and the doctors had all but given up. There was nothing wrong with me according to mainstream medicine.

But my life was falling apart, and I had to decide. Either figure this thing out. Or give up and die. I decided there must be a better way. Nootropics Saved My Life I’m a Virgo. And this means I’m very methodical in my approach to life. There had to be another answer to my cognitive problems. And thus began more years of research and experimenting. I had to find out if there was an alternative way to beat severe brain fog, memory loss and depression. Ritalin helped me focus. But was not helping in the memory and thinking department. Years of searching PubMed for clinical studies related to the issues I was dealing with, reading stacks of books, and combing through the forums. And little by little, I was able to get my brain working again. With determination and time, it is now working better than ever before. With the right combination of supplements and lifestyle changes, I’ve been able to turn my life around. My business is more profitable than ever, my relationship is better than the day we got married, and my brain is firing on all cylinders. And I continue to tweak and refine every area of my brain and cognition. Who This Book is For So if you’re dealing with ADHD. Or are not happy with your life because of brain fog, anxiety, depression, chronic fatigue, difficulty sleeping, OCD, memory loss or age-related problems … this book could be your way back. Nootropics and neuroscience are maturing. Researchers and ordinary neurohackers like us are beginning to understand a lot about the brain. And we’ve found that several things follow from taking care of your head first. Your quality of life is tied to how well your brain functions. If you give your brain what it needs, and slow down brain aging, boost your memory and alertness so you can think faster on your feet, and your brain begins to function the way it was designed or better – everything changes. My life, and the lives of millions of neurohackers worldwide is certainly testament to that! Think about this for a moment. You go to the dentist once a year to see how your teeth are doing. But you don’t think about going to your neurologist once a year to see how your brain is doing. Clearly your brain is more important than your teeth. You can get false teeth. But replacement brains are simply not yet available. One big lesson I have learned is your brain is not going to get better on its own. Researchers at Simon Fraser University in Canada studied 3,305 volunteers aged 16 to 44 years. They concluded that our brains start going south at age 24.2 This means that even if you’re living an optimal lifestyle, eating right, exercising, getting enough sleep,

and breathing clean air – your brain health on average starts to decline in your early 20’s. So this book is not just for neurohackers looking to tweak their brain for optimal performance. This book is for you if you want to do better in any area of your life. Including work, athletics, relationships, and spiritual life. Even your body’s overall physical health depends largely on how well your brain works. Take care of your head first and your life gets better. What is Your Brain Hacking Goal? This is an important question because when it comes to brain health and optimization, your options can be so overwhelming that you’ll put this book down. And never get started. Nootropic supplements can boost alertness, concentration, focus, memory and recall. And can reduce anxiety and depression. Some nootropics have even been proven effective in combating serious neurological diseases like ADHD, ADD, Alzheimer’s, Anxiety, Parkinson’s, Obsessive Compulsive Disorder (OCD), Traumatic Brain Injury (TBI), PTSD, and Major Depressive Disorder. So my advice is to first choose one area of your life that you’d like to improve. Maybe you’d like better memory. Or you’d like a healthier, more effective alternative to treating depression than with prescription SSRI’s. Maybe anxiety is destroying your quality of life. Nearly every area of your life can be improved with the right nootropic supplements. How to Use this Book This book is divided into sections that are easy to find and navigate. The first part of the book (Top 7 Brain Hacking Principles) explains how to get started with nootropic supplements. What to expect and how to choose the right supplement. General principles that will help keep you safe. And how to evaluate your progress as you try different supplements. The next chapter talks about “How Your Brain Works”. I’ve done my best to keep the neuroscience as simple to understand as possible. While giving you the fundamentals of what’s going on in your brain. And how nootropic supplements affect each area for desired results. The next section is the longest and provides you with a list of 102 nootropic supplements. Each supplement has an overview of what it is and what it helps in your brain, what goes wrong and why you may need it, how the nootropic feels when you take it, plenty of clinical research to back up what I’m saying, recommended dosage and side effects. Including drug interactions and where you need to be cautious if you’re using any prescription medications. Most of the nootropic supplements I talk about in this book are available at your local vitamin shop or health food store. The racetams are now much more difficult to get but can be purchased online from a couple of reputable supplement suppliers.

One thing you’ll notice is I don’t talk much about “Smart Drugs” that are commonly referred to in the press as nootropics. However, you may see me reference ADHD stimulants like Adderall or Ritalin. And possibly mention other prescriptions drugs like Modafinil. “Smart Drugs” are NOT nootropics. Anything that requires a prescription to purchase is considered a Smart Drug. Natural nootropic supplements can be purchased online or at your local health food store or vitamin shop. You do not need a prescription to buy nootropic supplements. And that distinct difference is reflected in this book. I want you to have the best experience possible while optimizing and repairing your brain. And not have to beg your doctor for a prescription. The section after the list of individual nootropic supplements in this book provides recommendations for specific brain-hacking goals. I talk about nootropics that have been shown to help specific brain functions. This will help you choose between the various supplements you’ve just read about. Brain functions including decision-making and thinking, anxiety and depression, energy and motivation, memory, and antioxidants and repair. The closing chapter provides instructions on “How to Build Your Nootropic Stack”. Think of that chapter as a recipe that when assembled, will help you achieve whatever you’re trying to fix or optimize. The very end of the book includes a glossary and index. The glossary can be handy to look up words you’re unfamiliar with. And the index of course is a ready reference to the entire book. This book is not meant to be read cover-to-cover like a novel. It’s more like a reference and repair manual for your brain. And the supplements that can help it. I suggest you keep this book handy as you first build your nootropic stack. And refer to it when you hear about something new that you think you’d like to try. Bookmark it, highlight it, write in the margins, circle things – do whatever you need to do to make this book work for you. The next section is my Top 7 Brain Hacking Principles. To get you started in hacking your own brain. And keeping you safe while you’re experimenting. Good luck. And remember. Fix your Head First. And most of the other important things in your life will fall into place.

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TOP 7 BRAIN HACKING PRINCIPLES Walk into any Vitamin Shoppe, drug store or shop online and you’ll have thousands of different supplements to choose from. Go to the brain optimization section, and your selection is reduced to a few hundred nootropic supplements. With this smorgasbord of racetams, vitamins, herbs, amino acids, and peptides within easy reach, you may be tempted to buy a variety of them for your nootropic stack. But I recommend taking a more cautious approach to hacking your brain. Ideally, you should be talking to your health-care provider to make sure these supplements will not interact with any of your prescription medications. However, let’s get real, and consider the state of medicine in many countries including the United States. Your doctor likely has no idea what you’re even talking about. Especially when it comes to natural nootropic supplements. In fact, hundreds of doctors, nurses, chiropractors, naturopaths and other medical professionals have subscribed to the Nootropics Expert newsletter and bought the 1st Edition of Head First. But fear not because we’ve got you covered. In the Chapter “Nootropics List”, each nootropic has a section detailing side effects including interactions with many prescription medications. But don’t rely exclusively on the medication interactions included in this book. Each nootropic could have many more interactions than I have been able to include in this book. Please do your own research online for each prescription medication you are taking. And review the contraindications, side effects & drug interactions, warnings and precautions lists for each medication. See how they work in your body and brain. And if there could be any kind of problem combining it with any of the nootropics in your stack.

There is No “Magic Pill” Bradley Cooper’s character in the blockbuster film Limitless took just one pill called NZT-48. And suddenly had perfect recall, could access the tiniest of snippets of past information, and turned them into advanced powers of deduction. His whole brain came alive. Making him seemingly super-human. If you are looking for your version of NZT-48 in nootropics, or any supplement or prescription drug, it doesn’t exist. It can’t exist. And here’s why. Your brain is arguably the most complex thing in the entire universe. The number of biochemical and bioelectrical processes going on in your brain right now, are mind-blowingly complicated. We have been conditioned by Western medicine in our modern society to choose one pill to fix a health problem. Every disease or health problem has a separate pill. And if the pill you’re prescribed causes a

side effect, you’ll get a prescription for the side effect. Of course, the antidepressant may not work. Or makes you sleepy. So you get another pill to keep you awake. And it goes on and on and on… Let’s put a stop to this nonsense right now. And look at how they’ve done it for several thousand years in the Far East and Native Americans. Healers in China and India know that your body and brain need a variety of nutrients in small doses instead of one high dose nutrient or drug. Ancient Chinese medicine, and Ayurveda from India, have known this for millennia. Their formulations include small amounts of several natural ingredients. Ancient doctors learned long ago that many medical conditions respond better to a combination of several active nutrients, instead of just one. Taking a high dose of one nootropic supplement can upset the delicate balance of the complex biochemical interactions in your brain. Western medicine is always looking for that one “magic pill” that alone will cure all ills. One pill to cure Alzheimer’s. Another pill to cure dementia. Yet another pill to cure depression. But your body and brain is far too complicated, with far too many processes going on every instant. One pill is not the answer to everything that can go wrong in your brain. Or that causes disease. With nootropics and brain optimization we must intelligently combine a variety of solutions.

Dosage and Synergy One of the most critical things to understand in using nootropics is that your stack must work synergistically. Because each supplement has a different mechanism of action in your brain and body. And each supplement in your stack should support the other nootropics in your stack. For example, acetylcholine’s function in your brain is needed for encoding new memories, reasoning, concentration, cognition and growth of new neurons (neurogenesis). Once acetylcholine does its job, the enzyme acetylcholinesterase comes in and breaks down acetylcholine. You can increase acetylcholine in your brain by adding Alpha GPC, CDP-Choline with Acetyl-LCarnitine (ALCAR) to your stack. But if you use more than one acetylcholine (ACh) precursor or supplement, you can boost ACh too much. Excess ACh can cause depression, irritability, muscle pain and a host of other problems. Also keep in mind that a nootropic like Huperzine-A inhibits acetylcholinesterase. Which increases ACh levels in your brain. So if you are using Hup-A in your stack, you may want to cut back on your dose of Alpha GPC, CDP-Choline or other choline supplement. Many nootropic supplements either increase ACh or inhibit acetylcholinesterase. If you take more than one choline supplement, you’ll hit a ceiling and not get a synergistic effect.

The same holds true for other neurotransmitters. And many other supplements explored in the Nootropics List section of this book.

Start Low and Slow Every nootropic has an ideal dosage for you. If you take more than your brain needs, you could have a negative reaction. And depending on the supplement, your reaction could include feeling anxious, brain fog, depression, slow thinking, irritability, restlessness, or feeling overly stimulated. This is particularly dangerous when boosting dopamine or serotonin too much. I’ll cover these neurotransmitters in more detail in the next section “Stay Safe”. Some nootropics, like most of the B-Vitamins are used by your body and brain. And the excess is excreted in your urine within a few hours. But other nootropics have a cumulative effect. And build up over time. A classic example of this effect is drinking too many cups of coffee. One or two cups give you an energy boost. But 3, 4, or 5 cups can have a cumulative effect and leave you irritable or feeling anxious. Combining a stimulant like caffeine with certain nootropics which also have a stimulant effect will produce similar symptoms of anxiety or irritability. And each of our bodies is unique. So you can’t predict how your body and brain will react to a supplement unless you try it. Start with a low dose of any new nootropic you’re adding to your stack. And gradually increase it over the next few days to see how your body reacts. Sometimes you’ll see recommendations of higher doses for certain nootropics. Especially on supplement packaging. These dosages are often based on clinical studies. Researchers were using a high dose to elicit a specific response within the time parameters of the trial. If you intend on taking the same nootropic over an extended period, it’s very possible that you will need a fraction of the dose used in the trial. You’ll notice this as you read forum threads. People experience a wide range of responses to different amounts for each nootropic. Our body and brain are unique. And influenced by genetics, the food we eat, what we drink, environmental toxins and a host of other things that affect us. Starting low and slow with any nootropic will minimize side effects. With experience, you’ll soon learn how much of each nootropic produces the best effect for you. You should also be skeptical of dosages listed on product labels. This advice goes for nootropics and even your prescription medications. Supplement companies and doctors don’t know your body as well as you do. Some people are very sensitive to nutrients and medicines where even a very small dose can produce nasty side effects. It’s OK to break pills in half or quarters, or open capsules and only use a small amount until you see how your body reacts. A small dose may be all you need.

You’ll often see in nootropics forums the letters YMMV. It stands for “Your Mileage May Vary”. Which means your reaction to a nootropic could be very different to the person standing next to you. I’ll say it one more time. Then leave it alone. For now. Start low and slow.

Avoid Tolerance With nootropics and many prescription drugs, developing tolerance means that over time your body doesn’t respond to that substance as well as when you first started using it. This doesn’t always mean it suddenly stops working. It just seems to become less effective over time. Not all nootropics are susceptible to tolerance. It’s typically an issue with some of the racetams like Phenylpiracetam. And Phenibut users can quickly build up a tolerance when using this nootropic. I talk more about tolerance for specific individual supplements later in this book. Many prescription meds also come with tolerance problems. Particularly stimulants like Adderall and Ritalin. Even many SSRIs used for depression and anxiety. Tolerance is caused in several ways in your brain and body depending on the substance. For example, many have tolerance issues with Adderall. And I’m going to use Adderall to illustrate how this works in your brain because there is some parallel here to understanding the cause of tolerance with some nootropics. Adderall in your brain alters dopamine concentrations and receptor densities, as well as calcium ion influx at NMDA receptor sites. Constantly triggering an excess influx of calcium ions through NMDA receptors alters synaptic plasticity, neuronal connectivity, and could even cause neuron damage. Over time, changes in NMDA receptor function from excess calcium ions could be part of the cause of tolerance. Now this gets a little complicated so stick with me here. Adderall works by boosting certain proteins (TAAR1) and inhibiting monoamine transporter molecules (VMAT2) in your brain. TAAR1 agonism decreases firing of dopamine receptors. And increases protein kinase signaling to the dopamine transporter (DAT). This modification of proteins stop DAT from functioning. Or affect transport of dopamine to the synapse. And VMAT2 inhibition triggers a release of dopamine from presynaptic vesicles into intracellular fluid. This all results in dopamine depletion in parts of your brain. Leading to tolerance due to low levels of dopamine. To make matters even worse, there’s some evidence that Adderall facilitates the expression of CREB (cAMP response element binding protein) in dopamine terminals. This induces the transcription of various genes which may also cause tolerance in some neurohackers. The bottom-line is concentrations of dopamine, norepinephrine and possibly even serotonin are affected by Adderall. But it depletes dopamine the most. Leading to tolerance. And why Adderall over time

doesn’t work as well as it once did. Enough of the neuroscience already. My point is that these types of shenanigans in your brain that can be caused by prescription meds and certain nootropics. Using some of these drugs can deplete certain neurotransmitters, and the density of neuroreceptors. Nootropics and drugs can alter gene expression in brain cells. They can affect hormone levels and cause oxidative stress in brain cells. Receptors are downregulated and you experience synaptic reorganization. And some neurotransmitter transporters decrease. The result is tolerance. So, we need a strategy to counteract this affect. But there’s not one blanket approach to avoiding tolerance because each nootropic or drug works differently in your brain. And even differently for different people. Often, the simplest strategy is cycling the substance you are using. Once you feel you’re not getting the affect you once did, it’s time to stop using that nootropic for a while. Allow your brain to recover before you start using it again. Another strategy is compensating for what’s causing that tolerance in the first place. For Adderall, you could add NDMA antagonists like magnesium, zinc or Huperzine-A to your stack. You could upregulate dopamine by using L-Tyrosine which boosts dopamine levels, or Inositol which increases dopamine D2 receptor density. Or choline which also increases dopamine receptor densities. And even Sulbutiamine which increases the number of dopamine binding sites. Personally, I find that using 1000 mg of DHA in the morning, with 500 mg L-Tyrosine, 750 mg Aniracetam, and 400 mg Sulbutiamine along with 300 mg CDP-Choline and 500 mg ALCAR every time I take my dose of Ritalin (twice per day), prevents tolerance. And an extra dose of these nootropics around 4 pm also prevents the stimulant crash that normally comes with using a stimulant like Ritalin. My final advice on tolerance is research each nootropic you are using. Find out exactly how it works in your brain. And if there is a potential for tolerance, find out what you can do to avoid it. Comments on the Nootropics Expert website and YouTube channel can be useful too. But you’ll find that every person in a thread has a different opinion on how to avoid tolerance for a nootropic or prescription med. You must decide for yourself by listening to your body and how it’s reacting. That, combined with your knowledge of a nootropic will provide you with a plan of action to deal with tolerance.

Choosing the Right Nootropic This entire book is about choosing the right nootropic supplements to help address your specific cognitive issues. So, here I’ll talk about a couple of examples that could help you build your nootropic stack.

In the previous section, we explored how using certain nootropics or prescription drugs can affect various parts of your brain. Stimulants like Adderall and Ritalin and their kin can deplete dopamine in your brain. Among other issues which we also covered. To replenish dopamine stores in your brain requires finding out what natural substances can help your brain produce more dopamine. And once you’ve made a list of dopamine-producing options, choose one and try it. One strong word of caution. You may have a list of several natural compounds that help your brain produce dopamine. Don’t try using all of them at the same time. Because if you boost dopamine too much, you’ll experience some nasty side effects. Including irritability, aggression, intense sexual feelings and worst case is psychosis. The same goes for boosting any other neurotransmitter or cognitive function in your brain. Carefully choose a nootropic, get the dose right, take it and see how you react. If it doesn’t produce the effect you want, then try something else. You can also have an unpleasant experience by taking a nootropic at the wrong time of day. For example, if you use a supplement that acts as a stimulant while indoors and strapped to your desk, you could feel restless and irritable. On the other hand, using the same nootropic with stimulant effects during the weekend could give you the energy to enjoy that mountain hike more. Or a more enjoyable bike ride, or time with your kids. So, it’s not only important to choose the right nootropic, or nootropic stack, but also that you match the right circumstance, day, and time or setting. Many of the nootropics discussed in this book act as stimulants. Including Tyrosine, DHEA, Citicoline, Ginseng, Gingko Biloba, Coenzyme Q10, SAMe, DMAE and even high doses of B-Vitamins. When combined, their effects can be cumulative and lead to overstimulation or insomnia. It took me several years to settle on exactly what I needed in my personal nootropic stack. And my wife gave me a hard time about the money I was spending on supplements every month. But I no longer get complaints about money spent on supplements. Because the result has been a complete turnaround in my health including the bedroom. My income is higher than it ever was. And it keeps on getting better. Experimenting is your key to success in biohacking and brain optimization. Stick with it and the miracles start to happen.

Stay Safe Earlier in this chapter I touched on the hazards of messing with neurotransmitters in your brain. Let’s take a closer look at things to watch out for when using nootropics. Some supplements can accumulate in brain cells, organs, and tissues over time. Meaning the more you

take, the more they build up in your body. With those types of nootropics, you need less, not more the longer you use it. I personally find I must re-evaluate my stack from time to time. And reduce dosages if I find I’m becoming over-stimulated or experiencing other side effects. Every nootropic supplement I’ve included in this book have positive effects on the brain and mental health. But high doses of some can have nasty effects which I cover in more detail in each relevant supplement review later in this book. Let’s look at a couple of examples here. We’ll start with dopamine. Dopamine is associated with feelings of pleasure and reward. This neurotransmitter plays a vital role in motivation and reward behavior. Drugs, food, and sex are all capable of boosting dopamine levels in your brain. Increased levels of dopamine can enhance your concentration, improve your mood, and even make you more sociable. But combining L-Tyrosine with Mucuna Pruriens (L-DOPA), and L-Theanine, which all affect dopamine levels, and you could have issues. Too much dopamine can result in agitation, anxiety, over-amped cognitive function, hyperactivity, hypersexuality, insomnia, and even psychosis. And excess dopamine suppresses serotonin. Serotonin plays a role in appetite control, mood, learning and memory, and sleep. Low serotonin is widely believed to be the underlying cause of depression. But too much serotonin can also cause big problems. And this can happen much more easily than you’d expect. Selective serotonin reuptake inhibitors (SSRIs) like Paxil, Prozac, Zoloft, Celexa, and Lexapro are used by millions to relieve depression by either boosting serotonin levels, or somehow affecting how serotonin works in the brain. But combining one of these SSRIs with nootropics like tryptophan, 5-HTP, or St. John’s wort which also boost serotonin, can lead to excess serotonin levels in your brain. Leading to Serotonin Syndrome which is a real danger, and one I’ve personally experienced. Excess serotonin can cause agitation, restlessness, diarrhea, nausea, vomiting, and rapid changes in blood pressure. When serotonin levels are excessively elevated, your headed for Serotonin Syndrome. And it’s much easier than you’d expect to enter this danger zone. Simply combining 5-HTP with an SSRI and you’re asking for trouble. Serotonin Syndrome symptoms include high fever, irregular heartbeat, seizures, loss of consciousness and even death. And I’m not kidding. My doctor’s fiancé died from Serotonin Syndrome. Staying safe when using nootropics means knowing exactly how they work in your brain and body. Learning how two or more nootropics interact. And reviewing the contraindications and warnings for every prescription medication you’re on.

Evaluating your Nootropic Stack Earlier I mentioned that my personal nootropic stack changes from time to time. I find something I want to try, compare it to my current stack, then decide if I need to eliminate something before adding it. As you gain more experience with neurohacking and nootropics, you’ll likely do the same thing. Testing and evaluating are part of the nootropic experience. And key to success with optimizing your brain. Nootropics can have dramatic benefits touching every part of your life. But just because something is within easy reach on a vitamin store shelf doesn’t mean it’s safe to use. You could be that one person in a thousand who has a bad experience. Does that mean that nootropic should be banned and taken off the market? I don’t believe that’s the answer. Each of us must take personal responsibility for our body and brain. And decide what to use to enhance cognition. Or not to use.

Your Brain is Part of a System When you take the nootropics presented in this book for optimizing your brain, they not only have an effect on your brain, but on many other organs and tissues. Most nootropics I’ve included in this book have positive effects on both physical and cognitive health. But high dosages of some could cause side effects. In some cases, very severe side effects. You’ll find more on precautions and side effects in my review for each individual nootropic. Whenever you’re considering adding something new to your stack, carefully read the review for that nootropic. And keep in mind how it may affect your entire body. Not just your brain. One more thing… ever wondered why you get butterflies in your stomach? Or why an impending decision can cause an attack of intestinal cramps? They happen because your body has two brains. You’re already familiar with the one in your head. But there’s another vitally important one found in your gut. Like Siamese twins, your two brains are connected. When one gets upset, the other does too. Your gut has a powerful influence on all things brain related. I’ll not go into detail here because this book is about ‘nootropics’. Just realize that all the nootropics you take start in your digestive system. Unless you take it sublingually. And can have effects starting in your gut. And all the way up until it crosses your blood-brain barrier. You can learn more about your microbiome and how it affects cognition and mental health by doing an online search. Or going to NootropicsExpert.com and searching for my article called “Psychobiotics: The Gut-Brain Connection”. We’ll investigate in detail each of 102 nootropics in detail in the next chapter. I’ve tried most of the supplements discussed in this book. They all work, and I have my favorites that I use every day.

My dearest wish is that you find your ultimate nootropic stack. Start optimizing your brain and being feeling better today. But first, I have found through thousands of hours of research that it helps to understand how your brain works. Understanding the neuroscience even a little helps you understand why you are choosing a specific nootropic. It takes the mystery out of building your own nootropic stack. And reduces the feelings of overwhelm. Next up is how your brain works. You’ll be amazed once you learn what’s going on in that skull of yours.

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HOW YOUR BRAIN WORKS Your brain is the most complex organ in your body. And many speculate the most complex thing in the entire universe. Weighing only about 3 pounds (1.36 kg), your brain is the command center for intelligence, interprets what you feel, hear, smell, taste, controls body movement and functions, directs your behavior and more. People have been fascinated by the brain since Aristotle in ancient Greece. But until recently the brain was considered too complicated to understand. Times have changed and scientists have learned more about the brain in the last 10 years than in the last several thousand years. The rate of research in neurobiology and behavioral science has accelerated. As has new research techniques. As a result, we know more about how nootropic supplements work. And can fine-tune our stacks to get the results we want. This chapter will help you understand how your brain works. We’ll touch on how to keep it healthy and optimized. And what happens when the brain is diseased or dysfunctional.

Brain Architecture Your brain is like a highly skilled team of professionals. Everyone working together, but each with their own unique job function. This macro view divides your brain into three basic teams: forebrain, midbrain, and hindbrain. The upper section of your spinal cord, the brain stem and a ball of tissue called the cerebellum (Latin for ‘little brain’) make up the hindbrain. This team controls your body’s vital functions like heart beat and breathing. Your cerebellum also coordinates movement and plays a role in learned movements. Like reaching for a glass when you want a drink. When you play your guitar, or kick a football, you are activating your cerebellum. The very top of your brain stem is called the midbrain. This team controls your reflex actions. And plays a role in controlling eye movement and other voluntary movements. The forebrain is the most highly developed and largest part of your brain. This team consists mainly of the cerebrum. And the structures buried beneath the cerebrum including the hippocampus, basal ganglia and olfactory bulb (sense of smell). The cerebrum is the uppermost part of your brain and what you normally associate with the idea of what a brain looks like in pictures.

The cerebrum controls your emotions, hearing, vision, personality, all voluntary actions, and more. This is where intellect and cognition take place, where your memories are stored, imagination and thinking occur, and allows you to plan. The cerebrum is split in two halves or hemispheres. The two cerebral hemispheres are connected and communicate with each other via a thick cable of nerve fibers called the corpus callosum. The two hemispheres look alike but each has a unique function. Each interacts with the opposite side of your body. When the left side of your brain is damaged, the right side or your body is affected. For example, a stroke in the left hemisphere of your brain can leave your right arm and leg paralyzed.

Cognitive Architecture Each cerebral hemisphere is divided into ‘lobes’, each specializing in a different function. Let’s start with the two frontal lobes. The two frontal lobes are located directly behind your forehead. Imagining the future, planning a schedule or reasoned arguments are controlled by these two frontal lobes. The frontal lobes act as short-term storage for memory much like RAM in your computer. It allows you to keep one idea in mind while other ideas are considered. At the back of each frontal lobe is a motor area which helps control voluntary movement. Like lifting your arm or taking a step. Next door to the motor area is Broca’s area which allows thought to be transformed into words. The parietal lobes are right behind the frontal lobes. And are used for example when you savor a delicious meal. This is where smell, taste and texture are processed. The forward section of your parietal lobes (right behind the motor area) are sensory areas. This is where you receive information from the rest of your body about movement, taste, temperature, and touch. Arithmetic and reading are also governed by each parietal lobe. Occipital lobes are near the back of your cerebrum. As you look at the words on this page, images from your eyes are processed in the occipital lobes. And linked to information with images stored in your memory. Damage to your occipital lobes can cause blindness. Underneath the parietal and frontal lobes are your temporal lobes. When you listen to music, your brain responds through activity in the temporal lobes. An area at the top of each frontal lobe is involved in receiving information from your ears. The underside of each temporal lobe plays a role in forming and retrieving memories. Including those associated with music. Other parts of each temporal lobe help integrate memories and sensations of taste, sound, sight, and touch.

Cerebral Cortex

A 2 – 3 mm layer of tissue covering your cerebrum and cerebellum is called the cortex (Latin for ‘bark’). Also referred to as the cerebral cortex, this “gray matter” is where information processing takes place in your brain. The cerebral cortex is ‘gray’ because neurons in this area lack the protective layer that makes most other parts of your brain appear white (“white matter”). The folds you notice in pictures of the brain are there to add surface area to the cortex. Increasing this surface area increases the amount of gray matter and the volume of information you can process.

The Gatekeepers Deep within your brain is the “inner brain”. Here lie the gatekeepers between your spinal cord and cerebral hemispheres. These team members help determine your emotional state, modify your perceptions and responses depending on that state, and even allow you to initiate movements without thinking about them. Like the lobes in your cerebrum, these team members come in pairs which are duplicated in each half of your brain. The pearl-sized hypothalamus directs several crucial actions. It wakes you up in the morning. And gets the adrenaline flowing when you’re taking an exam or doing a job interview. Your hypothalamus is an important emotional center. Controlling neurotransmitters that make you feel angry, exhilarated, or unhappy. The thalamus is near your hypothalamus and a major clearinghouse for information traveling to and from your spinal cord and cerebrum. A curved set of nerve cells leads from your hypothalamus and thalamus to your hippocampus. This surprisingly tiny hub acts as a memory indexer. It’s like mission control when it comes to memory. Your hippocampus sends memories out to the appropriate part of your cerebrum for long-term storage and retrieves them when needed. Note that the hippocampus, while crucial to long-term memory, doesn’t store memories. In Alzheimer’s Disease, the hippocampus is one of the first areas of the brain to suffer damage. Disorientation and memory loss is some of the first symptoms in Alzheimer’s. Your basal ganglia are clusters of nerve cells surrounding the thalamus. And interconnected with your cerebral cortex, thalamus and brainstem. This area is involved in working memory. Your basal ganglia play a role in decision making, initiating, and integrating movements, learning and skill acquisition, procedural learning, reward processing, routine behaviors (habits), eye movement, cognition and emotion. Your basal ganglia transfers information that controls the release of dopamine. Parkinson’s Disease,

which results in rigidity, stiff and shuffling walk, and tremors, is a disease of the nerve cells leading to the basal ganglia.3

Neurons & Synapses Your Central Nervous System and brain are composed of many distinct types of cells. But the primary functional cell when choosing nootropics for optimizing your brain is a cell called the neuron. The most recent research estimates your brain has an average of 86.1 billion neurons, and 84.6 billion other types of cell including glial cells.4 Glial cells surround and nutritionally support neurons. And more recent research shows may even play a role in brain cell signaling and neuroplasticity. A neuron is a highly specialized cell for processing and transmission of cellular signals. Your mood, movements, memories and sensations are the result of neurotransmitters and electrical signals sent and received by neurons. Neurons consist of three parts: the soma (cell body), dendrites and an axon. The soma contains the nucleus which is the control center of the cell. The nucleus is comprised of DNA, mRNA, genes, chromosomes, and proteins. Dendrites are feathery branches extending out from the soma. And act as a type of ‘antenna’ to receive signals sent by neighboring neurons. Each neuron (nerve cell) has a single axon which can vary in length extending out from the cell. Axons act as the cell’s sending unit that allows it to communicate with a neighboring neuron. Each axon can have extensive branches allowing it to communicate with many target cells. The longest axon in your body is the sciatic nerve that extends from the base of your spine down to your toes. The axon terminal contains synapses which are special structures where neurotransmitters are released or collected to communicate with target neurons.

Cell Membranes Each neuron is encased in a cell membrane which separates the inside of the cell from the outside. This cell membrane acts like a barrier, allowing only the good stuff like water, oxygen, and nutrients to enter the cell. And restricts access to undesirable substances like toxins. The cell membrane consists mostly of lipids (fats) which include phosphatidylcholine (PC), phosphatidylserine (PS), DHA, and other lipids. This cell membrane is constantly changing, and is influenced by your diet, stress and your immune system. DHA, PC and PS are used as nootropics because manipulation of the composition of the lipids in cell membranes can influence the function of neurons. The cell membrane has two layers. The inner layer facing the inside of the cell. And an outer layer facing the outside. The two most common groups of compounds making up these layers include

phospholipids and sterols. Amino acids, fatty acids and phosphorous make up most of the lipids comprising phospholipids. Phosphatidylcholine (PC) makes up about 30% of the lipid content in your brain. Phosphatidylethanolamine (PE) makes up about 27% of the lipid content in your brain. And another 10% of your brain lipid content is phosphatidylserine (PS).5 Sterols include cholesterol which comprise about 20% of the lipid content of your brain. Cholesterol is a precursor from which steroid hormones like DHEA, progesterone, estrogen and testosterone are formed. Changing or altering the composition of brain cell membranes can have a profound impact on many aspects of brain function. In many instances, using Omega-3s containing DHA, or supplementing with PC or PS can influence cognition, memory and brain health. Often as important as changing neurotransmitter levels with the use of nootropic supplements.

Brain Cell Signaling Calcium, chloride, potassium and sodium ions in each brain cell has a different charge. And maintain a voltage gradient across the membrane of that cell. When the voltage changes significantly, an electrochemical pulse called an action potential is generated. This electrical activity can be measured and displayed as a wave form called Brain Waves. This electrical pulse travels along the cell’s axon. And is transferred across a synapse to a neighboring neuron. The neighboring neuron receives the signal through one of its dendrites. This transfer is known as a synaptic connection. A neuron can form tens of thousands of connections with other neurons. Some estimates report well over 100 trillion synapses.6 Related neurons can form neural networks. And the more signals sent between two neurons, the stronger the connection. With each new experience and each fact that you remember, your brain slightly re-wires itself on a physical level. This neuroplasticity is called long-term potentiation and is required for the development or encoding of long-term memories. Signaling between neurons is not only electrical, but also electro-chemical. An axon terminal contains thousands of sacs called vesicles. Each vesicle can contain thousands of neurotransmitter molecules. These neurotransmitters are like chemical messengers which amplify, relay, and modulate signals between neurons. When stimulated by an electrical pulse, a neurotransmitter is released. And crosses the synaptic cleft to the neighboring neuron. It then binds to a neuroreceptor in the dendrite of the receiving (post-synaptic) neuron.

Neurotransmitters

Every emotion or thought you experience is associated with electrochemical nerve impulses. And the release of tiny amounts of neurotransmitters between neurons. Electrochemical nerve impulses and the release of neurotransmitters in certain parts of your brain are happening as you read this sentence. Your eyes sense the shape of letters. And the information is relayed to your cerebral cortex. Your brain interprets these letters and words and convert them into thoughts. The thought is in turn stored as memory. Your genetic makeup, prior learning experience and memory dictate the nature of these thoughts. Another person reading this same sentence will experience it differently than you because no two people will have the exact same thoughts. Each brain is unique. Everything that you hear, see, smell, taste and touch is processed in your brain with electrochemical messengers. These messengers are neurotransmitters. Dozens of amino acids, amines, hormones, minerals, peptides and purines act as neurotransmitters. Influencing alertness, cognition, memory, and mood. But investigating all of these neurotransmitters is not necessary for our purposes. Instead, a brief explanation of some of the important neurotransmitters will help you understand how the nootropic supplements discussed in this book affect your cognition. I recommend you use this chapter as a reference. When you find a nootropic supplement later in this book that you find helpful, refer back to this section to learn more about its chemistry and function in your brain. The two most common neurotransmitters in your brain are glutamate and GABA (GammaAminobutyric Acid). Other crucial neurotransmitters include acetylcholine, dopamine, epinephrine, norepinephrine, melatonin and serotonin. Let’s start with a review of the two most abundant neurotransmitters in your brain; glutamate and Gamma-Aminobutyric Acid (GABA).

Glutamate Glutamate is the most abundant excitatory neurotransmitter in your brain. Glutamate is stored in synaptic vesicles. And when an electrical impulse is sent down the axon by the neuron, glutamate is released from the presynaptic neuron. At the receiving, or post-synaptic neuron, glutamate binds to glutamate receptors like NMDA or AMPA receptors which are then activated. Constant or frequent activation of glutamate receptors strengthen these interconnected synaptic networks. And contributes to the neuroplasticity and long-term potentiation associated with cognitive functions like learning and memory.7

Too much glutamate, or overly sensitive glutamate receptors can cause cell damage or cell death. And lead to restlessness, irritability, insomnia and even seizures. Scientists have discovered that NMDA receptors in people with Huntington’s Disease are overactivated by glutamate. You get glutamate from foods like meat, poultry, fish, eggs, and dairy products. Glutamate does not easily cross your blood-brain barrier. So, must be transported across by the high-affinity transport system. Glutamate is a precursor for the synthesis of the inhibitory neurotransmitter Gamma-Aminobutyric Acid (GABA).

GABA GABA (γ-Aminobutyric acid) is the most abundant inhibitory neurotransmitter in your brain. Neurons that produce GABA are known as GABAergic neurons. GABA does not easily cross the blood-brain barrier. But instead, is synthesized in your brain from the neurotransmitter glutamate using the enzyme glutamate decarboxylase (GAD) and pyridoxal-5phosphate (Vitamin B6 or P-5-P) as a cofactor. GABA’s primary role in your brain is to keep glutamate in check. Too much glutamate can cause a seizure. And too much GABA can put in you in coma. An optimized brain has a healthy balance of both GABA and glutamate. GABA helps reduce anxiety, insomnia, nervousness, restlessness and stress. When you take GABA as a supplement it can even increase human growth hormone.8 GABA receptors are stimulated by barbiturates and benzodiazepines which result in relaxation. And a reduction of irritability and stress. Brain disorders like epilepsy, sleep disorders and Parkinson’s disease are affected by GABA. Ashwagandha, Lemon Balm, Passionflower, Valerian root, Ginseng, Kava, L-Theanine, green, black and oolong tea help increase the effect of GABA on its receptors. The nootropic GABA is either synthetically formed and naturally-grown (PharmaGABA) GABA which helps increase GABA levels in your brain.

Acetylcholine Acetylcholine (ACh) was the very first neurotransmitter to be identified. Discovered in 1915 by British physiologist Sir Henry Hallett Dale who later shared the Nobel Prize in Physiology Medicine with Otto Loewi in 1936. Acetylcholine is made from choline and a two-carbon molecule called acetyl. It is synthesized in cholinergic neurons in your brain and body. Acetylcholine binds and activates two classes of receptors: muscarinic and nicotinic. You have two types of nicotinic receptors in your body: muscle-type and neuronal-type. The muscle-

type receptors are on muscle cells and are used to activate skeletal muscles and signal a body movement. The neuronal-type receptors have acetylcholine acting as a neuromodulator. Affecting attention, learning and memory. Once it is produced, acetylcholine is stored in cholinergic neurons and released into the synaptic cleft when stimulated by an electrical signal. When acetylcholine is released in the synaptic cleft, the enzyme acetylcholinesterase breaks acetylcholine back down into choline and acetyl. Alzheimer’s patients have a shortage of acetylcholine. And one of the ways doctors increase levels of ACh is to inhibit the acetylcholinesterase enzyme with prescription drugs. Leaving more acetylcholine available for cognitive function. Too much acetylcholine can result in continuous stimulation of muscles, glands, and your central nervous system. Which can even result in fatal convulsions. For example, nerve agents like Sarin gas act as acetylcholinesterase inhibitors and are used in chemical warfare. The Black Widow Spider has a similar effect to Sarin in that it inhibits acetylcholinesterase. The venom causes a massive release of acetylcholine, norepinephrine and GABA. Causing cramps, fast pulse, pain, and sweating. Nootropic supplements like Alpha GPC and CDP-Choline can boost levels of acetylcholine. Which is particularly important when using racetams like Piracetam that modulates AMPA and NMDA receptors. Piracetam also improves the flow of acetylcholine, and the sensitivity of ACh receptors. Huperzine-A is used a nootropic because it acts as an acetylcholinesterase inhibitor which boosts the use of acetylcholine in your brain. Improving memory, cognition and lucid dreaming.

Dopamine Dopamine is an amine synthesized from its precursor L-DOPA in your brain. It belongs to the catecholamine family of neurotransmitters which include epinephrine and norepinephrine. Dopamine must be synthesized in dopaminergic neurons in your brain from L-DOPA because it can’t cross the blood-brain barrier on its own. The primary pathway for dopamine synthesis is L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine. You get the first two amino acids in this pathway from protein-rich foods like eggs, chicken, liver, beer, milk, and soybeans. Boosting dopamine levels in your brain leads to better mood, alertness, sex drive and even heightened verbal fluency and creativity. Dopamine also controls muscle movement by modulating motor centers in your brain (e.g. basal ganglia) and may also regulate movement by directly controlling motoneuron function. Dopamine in your brain binds to dopamine receptors of which there are 5-types numbered D1 – D5.

After dopamine is synthesized in the neuron, it is transported to and stored in vesicles until it is ejected in the synaptic cleft. Upon arrival at the post-synaptic neuron, dopamine binds to and activates dopamine receptors located on dendrites of that neuron. Or presynaptic auto-receptors which are located on the axon of the presynaptic neuron. Once dopamine activates the receptor, it is released back into the synaptic cleft where it’s broken down by the enzyme monoamine oxidase (MAO). Bookmark that last sentence in your brain because many prescription drugs take advantage of that MAO action. Certain drugs block the activity of MAO and are known as MAO inhibitors (MAOIs). There are two types of MAO inhibitors – type-A and type-B. Both can act as antidepressants, and typeB inhibitors are also used to treat Parkinson’s disease. A decline in dopamine in your brain can lead to learning and memory problems, low sex drive, anxiety, or depression. And worst-case is movement problems like in Parkinson’s Disease. Later in this book we’ll explore the nootropics that influence or can boost dopamine levels in your brain.

Epinephrine & Norepinephrine The amino acids phenylalanine and tyrosine are converted into dopamine. Dopamine can then be converted into norepinephrine, and then epinephrine. When you take tyrosine as a supplement or get it from food, you can elevate dopamine and norepinephrine levels. Which leads to a boost in alertness and mood. Too much of these neurotransmitters can elevate blood pressure, heart rate, anxiety, irritability and insomnia. Some prescription antidepressants improve mood and boost arousal by increasing levels of epinephrine and norepinephrine. Several enzymes are required to convert phenylalanine all the way through the dopamine pathway to epinephrine. And these enzymes require cofactors like the B-Vitamins and other nutrients. For example, L-DOPA is converted to dopamine with Vitamin B6, B9 and B12 as cofactors. Dopamine is converted to norepinephrine with Vitamin C as a cofactor. And norepinephrine requires SAM-e to convert to epinephrine.

Serotonin Serotonin (5-HT) is a monoamine neurotransmitter. Serotonin is synthesized from 5-Hydroxytryptophan (5-HTP) with Vitamin B6 as a cofactor. And 5-HTP comes from the synthesis of Tryptophan which you get from meat, fish, and other protein foods. Once serotonin is synthesized in your brain, your pineal gland can use it to produce melatonin which is

used to govern your circadian rhythm and sleep cycles. We have a ton of research to draw on for serotonin because it affects such a vast range of psychological and biological functions. A team at the Cleveland Clinic first discovered serotonin in 1948. Serotonin regulates or is otherwise involved in anxiety, arousal, aggression, mood and cognition. Recall that we referred to dopamine and norepinephrine earlier in this chapter, and their effects on arousal and mood. Serotonin produces similar effects in your brain but works differently than the other catecholamines. However, serotonin receptors modulate the release of several neurotransmitters including glutamate, GABA, dopamine, norepinephrine, epinephrine and acetylcholine. Which would account for some of serotonin’s similar effects like that of dopamine and norepinephrine. Where they differ is too much serotonin can cause relaxation, sedation, and decreased sex drive. And can also cause aggression and anger. The antidepressant fluoxetine (Prozac®) is a selective serotonin reuptake inhibitor (SSRI) and acts to raise serotonin levels in the brain. Maybe even influencing other neurotransmitters in the brain. Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamine neurotransmitters (including serotonin) and increase concentrations of neurotransmitters in the brain. The nootropic 5-HTP is an immediate precursor to serotonin, and in some cases, can be used instead of SSRI’s. L-Tryptophan and St. John’s wort can also boost serotonin levels in the brain. And are often used as an antidepressant. When the serotonergic system gets out-of-whack, it can lead to anxiety, depression, improper social behavior and sexual problems. Other problems with serotonin in the brain include insomnia, obesity, eating disorders and even chronic pain. Low serotonin levels can be caused by not getting enough of its precursor tryptophan from food. And for tryptophan to be transported across the blood-brain barrier, it needs a carrier protein. The problem is that carrier protein is also used by other amino acids that need to cross into your brain. Including amino acids like phenylalanine and tyrosine which convert in your brain to dopamine and norepinephrine. Imagine this carrier as a very small boat that can only carry one person across the lake at a time. There is always competition for amino acids to jump on that little boat to get to your brain. So, brain levels of tryptophan are not only determined by levels of tryptophan in your bloodstream. But also, by the concentration of competing amino acids trying to get across and into your brain. You can supplement with L-Tryptophan to boost serotonin levels. Or its direct precursor 5-HTP. You can also use the nootropic Cat’s Claw which can also boost tryptophan levels which in turn can increase serotonin.

Improve Your Memory with Nootropics Looking for an edge to advance your career? How about more confidence and an easier time preparing for and writing that next exam. Preparing that next presentation. Or improving your mood and motivation to help your relationships. Nootropic supplements can help improve: • • • • • • • • • •

Alertness Arousal, libido, and sexual enjoyment Awareness, vision, hearing and sensory perception Concentration and focus Creativity and thinking outside-the-box Complex problem-solving abilities Learning and memory Mood, energy and vitality Speed of cognition and reaction time Verbal fluency

Research over the last couple of decades has shown that our brain has the remarkable ability to re-wire itself throughout life. Meaning we can not only retain our memories and stabilize our mood. But we now have the knowledge and ability to improve memory and boost mood while taming anxiety. These may sound like lofty promises. But I’m living proof along with thousands of others that improved cognition, better memory and mood, and an overall better quality of life is possible with nootropic supplements. Here I’ll touch on some of what’s happening in your brain. And how nootropics can help optimize brain function.

Types of Memory Scientists have identified several distinct types of memory. Including short- and long-term memory and working memory. Let’s look at each type with a brief explanation of what they are and how they work in everyday life. Short-Term Memory is also known as primary or active memory. It is characterized as being very brief (i.e., seconds), and is limited to what you can remember and retain for 20 to 30 seconds. Your brain can only retain new information to a certain extant (chunk capacity) and only temporarily (temporal capacity). Short-term memory includes things like thinking on your feet, making quick decisions, verbal fluidity, humor, and reaction time. Short-term memory can be improved with certain nootropics. Acetylcholine precursors like Alpha GPC and CDP-Choline, Kava, Rhodiola Rosea, Phosphatidylserine (PS), and Nicotine have been shown to help alertness, focus, short-term memory and mental clarity.

Long-Term Memory describes the type of memory associated with an event or information acquired by your mind long ago. It could be anywhere from a couple of days to a lifetime. These memories are often pieced together by the brain with inaccurate or imagined information. This memory storage can come from your perception of an event or thing, conditioning, or any other accurate or faulty input. Long-term memory relies on long-term potentiation (LTP) and the strengthening of connections between neurons and synapses. LTP relies upon brain-derived neurotrophic factor (BDNF). A naturally occurring protein in your brain that is responsible for the growth, maintenance, and survival of neurons. When BDNF is released in your brain, new connections form as BDNF attracts dendrites from neurons and connects them to neighboring synapses. As your brain cells fire together, they wire together. These tiny networks in your brain are how long-term memories consolidate and form. Nootropics to boost BDNF include Ashwagandha, Bacopa Monnieri, DHA, Gotu Kola, L-Theanine, Magnesium, N-Acetyl L-Cysteine (NAC), Noopept, Rhodiola Rosea, Pterostilbene, Resveratrol and Turmeric. Nootropics to boost long-term memory include Oat Straw, Nicotine, Nefiracetam, L-Glutamine, Forskolin, Tryptophan, Vinpocetine, Resveratrol, Pterostilbene, Phosphatidylserine (PS), Phosphatidylcholine (PC), Pramiracetam, Phenylpiracetam, Piracetam, Picamilon, Oxiracetam, NAcetyl L-Cysteine (NAC), Noopept, L-Theanine, L-Dopa, Magnesium, Ginseng, Huperzine-A, Lion’s Mane Mushroom, Coluracetam, and Artichoke Extract. Working Memory is distinct from short- and long-term memory. These are memories that are not only remembered, but simultaneously processed. You not only remember information that is important to you. You also remember the purpose of the information, and why you decided to remember it. Working memory uses different parts of your brain compared to short- and long-term memory. Researchers have identified activation in the prefrontal cortex, and other parts of the brain. Calling this model of brain computation FROST (short for FROntal-Striatal-Thalamic).9 Nootropics to boost working memory performance include Gotu Kola, Coluracetam, Creatine, Ginseng, Kava, Nicotine, L-Tyrosine, N-Acetyl L-Tyrosine (NALT), NADH, N-Acetyl L-Cysteine (NAC), Piracetam, Phenylalanine, Phosphatidylcholine (PC), Phosphatidylserine (PS), Pterostilbene, Turmeric, and Tryptophan. Each form of memory calls on specific pathways in your brain. Select neuroreceptors including AMPA receptors and NDMA receptors are involved in memory. Gene expression in the cellular nucleus. BrainDerived Neurotrophic Factor (BDNF), long-term potentiation, human nerve growth factor, neurogenesis, and more. The good news is we have control over how our memory works. And many natural nootropics to help boost and maintain the efficiency of these neural networks.

Memory and mood are complex subjects and each worthy of a book on their own. But instead of turning this into a book about neuroscience, let’s stay with how you can use nootropics to optimize cognition and mood. The next chapter goes into much more detail on how each nootropic featured in this book works, what it is, where it comes from, available forms, and dosage recommendations. For each nootropic, I also reference several clinical studies that support what neurohackers say about their experience with that nootropic.

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LIST OF NOOTROPICS Acetyl-L-Carnitine Acetyl-L-Carnitine may reverse age-related cognitive decline, and improve memory Acetyl-L-Carnitine (ALCAR, ALC or LAC) is a synthesized version of L-Carnitine. Which is a derivative of the amino acids lysine and methionine. L-Carnitine is an amino acid that’s synthesized in your body. You also get it from red meat and dairy. L-Carnitine is considered a “conditionally essential” nutrient because when your body uses it faster than it can produce it, you need supplemental L-Carnitine either from food or a supplement. L-Carnitine is used throughout your body. Here we’re talking about the Acetyl-L-Carnitine form of LCarnitine because of its effects on brain health and chemistry. L-Carnitine vs. Acetyl-L-Carnitine: What’s the Difference? L-Carnitine and Acetyl-L-Carnitine are often referred to as Carnitine. But each are structurally different, and each has its advantages. L-Carnitine: Can help increase energy production within mitochondria in your cells but is not capable of crossing the blood-brain barrier. Supplemental L-Carnitine is difficult for your body to absorb; only 18% of it reaches your bloodstream. L-Carnitine is favored by athletes and dieters who want Carnitine’s fat-metabolizing benefits. But are not seeking any brain benefits. Acetyl-L-Carnitine: Is easier to absorb and use by your body than L-Carnitine. One study showed using 2 grams daily for 50 days boosted blood ALCAR levels by 43%.10 ALCAR does everything that L-Carnitine does but can also cross the blood-brain barrier. In another study, researchers found that ALCAR protects brain cells from oxidative stress, while L-Carnitine does not.11 How does Acetyl-L-Carnitine Work in the Brain? Acetyl-L-Carnitine boosts brain health and function in several ways. But two in particular stand out. 1. ALCAR boosts acetylcholine, a neurotransmitter tied to memory and overall brain function. Acetyl-L-Carnitine is a precursor to acetylcholine in the presence of Coenzyme-A. ALCAR donates a “methyl group” to make acetylcholine.12 Alzheimer’s-diseased brains show a 25% to 40% reduction in carnitine acetyltransferase, a brain

enzyme that works with L-Carnitine & Acetyl-L-Carnitine. This brain enzyme decline led researchers to link low ALCAR with low acetylcholine, and Alzheimer’s onset. They went on to suggest ALCAR as a viable therapy for brain regeneration.13 2. ALCAR promotes brain energy by helping increase fuel production in your brain cell’s mitochondria.14 ALCAR works as a shuttle transport for fatty acids through cell membranes. And into mitochondria.15 • •

ALCAR shuttles fatty acids into mitochondria which contributes to adenosine triphosphate (ATP) synthesis, and which is your most fundamental source of energy. ALCAR also shuttles fatty acids out of mitochondria, and helps flush out toxic byproducts.

ALCAR supplies fatty acids for mitochondrial energy production in nearly every cell of your body. Your brain consumes at least 20% of your body’s energy. And generates a lot of toxic byproducts. So ALCAR is particularly important for a healthy brain. How things go bad As we get older, our brain chemistry and energy metabolism changes.16 ↓ Nerve growth factor in the brain declines ↓ Acetyl-L-Carnitine levels decline ↓ Acetylcholine levels decline ↓ Mitochondria lose efficiency All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. ALCAR benefits Research from the Linus Pauling Institute at Oregon State University shows that Acetyl-L-Carnitine will:17 • • •

Restore efficient mitochondrial energy production Replenish age-related changes to mitochondrial structure Replenish ALCAR and acetylcholine levels in the brain and body

ALCAR has the ability to boost acetylcholine and rejuvenate brain cells (including mitochondria). This has been proven to benefit those with age-related brain diseases like Alzheimer’s and major depression.18 How does Acetyl-L-Carnitine feel? You may not feel ALCAR… unless you’re elderly or have Erectile Dysfunction. Within those specific groups, Acetyl-L-Carnitine helps with memory, mood, mental performance and the ability to get and

maintain an erection. ALCAR’s brain support and its ability to help create ATP in mitochondria in your brain cells should boost cognition in all age and gender groups. As a nootropic, ALCAR user reviews report a boost in energy and quick thinking. The Research In one study, researchers showed that ALCAR may have positive effects for depression and dementia.19 Another study out of Italy; researchers showed that Acetyl-L-Carnitine stimulated the growth of new neurites. More of these minute projections from nerve cell bodies meant increased signaling between cells throughout the central nervous system (brain and spinal cord).20 ALCAR helps with Mild Cognitive Impairment (MCI) A gold-standard double-blind, randomized controlled trial on 1,204 people showed a significant effect on attention, mental performance, memory and higher mental functions.21 In this study ALCAR seemed to ward off further brain deterioration. And could be considered as therapy for brain degeneration. Acetyl-L-Carnitine slows rate of cognitive decline 130 Alzheimer’s patients were given ALCAR or a placebo daily for a year. They were tested across 14 points of cognitive performance. This research showed a slower decline in cognitive performance with the ALCAR group compared to the placebo group.22 ALCAR effective for Chronic Fatigue Syndrome Acetyl-L-Carnitine has been shown to improve fatigue in patients with chronic fatigue syndrome. In a randomized, double-blind, crossover study; 36 people were treated for 3 months with either amantadine (used to treat Chronic Fatigue), or 1 gram of ALCAR twice daily. The results of the study showed that ALCAR was better tolerated and more effective than the pharmaceutical for fatigue.23 Acetyl-L-Carnitine protects from oxidative damage of Ecstasy (MDMA) Research has shown ALCAR to be effective in protecting your mitochondria from oxidative stress. And the use of MDMA can cause oxidative damage in mitochondria. In this study, male rats were given Acetyl-L-Carnitine before a dose of Ecstasy (MDMA). ALCAR pretreatment “exerts effective neuroprotection against MDMA-induced neurotoxicity at the mitochondrial level”, said the researchers.24 Keep that in mind before your next party.

ALCAR for Erectile Dysfunction In this study, 120 patients were split into 3 groups. Group 1 was given 160 mg of testosterone per day. The 2nd group was given 2 grams of Propionyl-L-Carnitine plus 2 grams of Acetyl-L-Carnitine per day. And the 3rd group a placebo. Did you know that there’s an International Index of Erectile Function? Turns out the Propionyl-L-Carnitine/Acetyl-L-Carnitine stack was better than testosterone for erectile dysfunction. Without the side effects of an enlarged prostate, better organisms, more sexual desire, and improved mood.25 Dosage Notes • • •

Acetyl-L-Carnitine suggested dosage for cognitive benefit is 1 – 4 grams per day. For improved mood and elimination of chronic fatigue, 1 – 3 grams of ALCAR per day. For age-related memory concerns, 1 – 2 grams of ALCAR per day.

Side Effects Acetyl-L-Carnitine is produced naturally in your body. So is considered well-tolerated and safe. Side effects are rare but can include nausea, vomiting, increased agitation, weight loss, and restlessness. You can also experience an increase in seizure frequency if you have any kind of seizure disorder. Available Forms • • •

•

Acetyl-L-Carnitine: L-Carnitine with an extra acetyl group. This version is more bioavailable and easily crosses the blood-brain barrier. L-Carnitine: This is the standard form of carnitine found in food. Lipo-Carn®: A proprietary blend of Alpha-Lipoic Acid and Acetyl-L-Carnitine. Studies show this combination is a powerful anti-aging duo. Together, these two help combat diabetes, boost energy production, maintain proper cognitive function, protects the body from radiation and chemical toxins, and helps immunity.26 Propionyl-L-Carnitine: L-Carnitine combined with propionic acid. This form is noted for its antioxidant activity and is used for heart health applications. Also useful for erectile dysfunction. Nootropics Expert® Recommendation

Acetyl-L-Carnitine 500 – 1,500 mg per day I recommend using Acetyl-L-Carnitine as a nootropic supplement. Your body does synthesize some ALCAR on its own. And from the food you eat. But most Acetyl-LCarnitine comes from red meat. And unless you eat a lot of high-quality grass-fed beef or mutton… ALCAR is especially helpful for those suffering from age-related cognitive decline. Studies show it helps stop or reverse brain degeneration with Alzheimer’s Disease, and depressive disorders.

Particularly in the initial stages of the disease. I suggest starting with a dose of 500 mg daily. ALCAR is a great compliment to a stack including Piracetam. Add a choline source (Alpha GPC or CDP-Choline) typically at a ratio of 1:4. 1 gram of CDP-Choline to 4 grams of Piracetam. Take just enough choline to eliminate a racetam-induced headache. Then add 500 mg of ALCAR. Some have found ALCAR stacked with Coenzyme Q-10 has a profound effect on everything from mood to bipolar disorder. Especially combined with Alpha-Lipoic Acid. Age-related cognitive disorders like Alzheimer’s may want to up the dose to 1,500 mg per day.

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Alpha GPC Alpha GPC has been shown to reverse age-related cognitive decline, improve memory and learning, and boost athletic workouts Alpha GPC (L-Alpha Glycerylphosphorylcholine, choline alfoscerate) is a choline source derived from soy or sunflower lecithin. It is also naturally present in small amounts in your body. You can also get it from eating organ meats, dairy and wheat germ. Choline is considered an essential nutrient because when your body uses it faster than it can produce it, you need supplemental choline either from food or a supplement. You need choline for synthesis of the neurotransmitter acetylcholine. And is part of phosphatidylcholine (PC), used in building cell membranes. In fact, choline is so vital to cognition and nerve function that, without it, we couldn’t move, think, sleep or remember anything. Alpha GPC is used throughout your body. It even helps the production of human growth hormone. Athletes use it for peak performance, and to help build lean muscle mass. It provides more energy for a workout and quicker recovery.27 Here we’re talking about how Alpha GPC affects your brain health and chemistry. Alpha GPC vs. CDP-Choline vs. Choline Bitartrate: What’s the Difference? Choline is a water-soluble nutrient, and its composition is similar to B-vitamins. Alpha GPC, CDPCholine, Choline Citrate and Choline Bitartrate are all sources of choline. CDP-Choline (cytidine 5′-diphosphocholine): Is only about 18% choline by weight. Your body naturally synthesizes choline into CDP-Choline (Citicoline). It’s then converted to phosphatidylcholine (PC) which assists cell membranes and helps create acetylcholine. Choline Bitartrate: An economical form of choline, and about 40% choline by weight. 1 gram of Choline Bitartrate offers 400 mg of actual choline. It does not easily cross the blood-brain barrier. So, you won’t experience the same level of nootropic benefit as with Alpha GPC or CDP-Choline. Alpha GPC: About 40% choline by weight and easily crosses the blood-brain barrier. Alpha GPC naturally occurs in your brain as a byproduct of phosphatidylcholine (PC). When your brain needs more choline, and the choline floating around in your brain is running low, it breaks down PC from cell membranes. And turns it into Alpha GPC. Your body and brain love it when you use Alpha GPC. Because it doesn’t have to cannibalize its own cells to get more choline.

How does Alpha GPC Work in the Brain? Alpha GPC boosts brain health and function in several ways. But two in particular stand out. 1. Alpha GPC boosts acetylcholine, a neurotransmitter tied to memory and overall brain function. Alpha GPC is a precursor to acetylcholine. Improving the efficiency of communication between neurons in your brain. This increase in neural signaling boosts memory, learning, cognitive processing and mental clarity. In one study, 32 healthy volunteers received either Alpha GPC or a placebo as a pretreatment. Ten days later they were injected with scopolamine to induce amnesia. The researchers found Alpha GPC was able to prevent the impairment of attention and memory normally caused by scopolamine.28 These researchers showed that memory function in young healthy people could improved. Simply by taking Alpha GPC as a supplement. 2. Alpha GPC directly impacts development of cell membranes in the cerebral cortex. This outer layer of neural tissues or “gray matter” is the information processing center of your brain. It controls intelligence, motor function, organization, personality, planning and touch.29 Published in Clinical Therapeutics, researchers conducted a double-blind, placebo-controlled trial with mild to moderate Alzheimer’s patients. 400 mg capsules were administered 3- times per day for 180 days. The conclusion of this trial showed consistent improvement in dementia patients given Alpha GPC.30 How things go bad As we get older, our brain chemistry and energy metabolism changes. ↓ Recall, reaction time and mood diminish ↓ Brain cell membranes degenerate ↓ Acetylcholine levels decline31 ↓ Nerve growth factor in the brain declines All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. But even if you’re not concerned with the effects of aging, Alpha GPC can help. Alpha GPC benefits Research from hundreds of studies have shown that Alpha GPC will: • •

Improve memory and learning ability32 Restore the bioavailability of acetylcholine33

• • •

Restore and boost nerve growth factor receptors in the brain34 Increase growth hormone in all age groups35 Boost cognitive performance and memory in Alzheimer’s patients36

Alpha GPC is water-soluble and quickly enters your brain after you take it. Once in your brain, it boosts signal transmission, and protects neurons. Alpha GPC improves your brain function and learning processes by directly increasing synthesis and secretion of acetylcholine. As your body calls for it. This form of choline is not a precursor to phosphatidylcholine (PC), but is a metabolite of PC. This means once PC is metabolized and stripped of its fatty acids – all that remains is Alpha GPC. Instead of scavenging your brain’s own membranes for Alpha GPC, you give it exactly the type of choline its looking for. How does Alpha GPC feel? If you have trouble getting started in the morning, try coffee and 400 mg of Alpha GPC. Instead of your usual high sugar, high carbohydrate breakfast. Alpha GPC can be a great way to boost your energy. Take it 45 minutes before you work out. Alpha GPC helps with memory, mood, mental performance and energy. Its brain support and ability to fuel the acetylcholine in your brain cells should boost cognition in all age and gender groups. The Research In one study, researchers showed that Alpha GPC had positive effects for increasing human growth hormone.37 Alpha GPC increases the release of dopamine Another trial demonstrated an increase in the release of dopamine.38 This is particularly significant in showing Alpha GPC can help those suffering from dopamine deficiencies. And alleviating the symptoms of diseases like depressive disorders, and Parkinson’s Disease. Alpha GPC facilitates learning and memory An ongoing trial demonstrates Alpha GPC improving memory and attention. This research shows Alpha GPC increasing the effectiveness of pairing it with donepezil (acetylcholinesterase inhibitor). Far better than using donepezil on its own. And in rats, Alpha GPC boosted learning and memory. It increased brain energy mechanisms and decreased age-related structural changes in the brain.39, 40 Alpha GPC relieves cognitive impairment in Alzheimer’s Thirteen published clinical trials, involving a total of 4,054 Alzheimer’s patients consistently showed Alpha GPC:41

• • • •

Boosted memory and attention Promoted recovery in stroke patients Reversed the symptoms of acute cerebrovascular disease Is far more effective than using choline or lecithin in treating disease

Dosage Notes Alpha GPC is about 40% choline by weight. So 1,000 mg of Alpha GPC provides approximately 400 mg of choline. • • •

Alpha GPC suggested dosage for cognitive benefit is 400 – 1,200 mg per day. Athletic training suggested dosage of Alpha GPC is 400 mg first thing in the morning, and another 400 mg dose 15 – 30 minutes before working out. Clinical treatment of Alzheimer’s Disease, dementia and other cognitive disorders dosage of up to 1,200 mg per day.

For higher dosages, split the daily Alpha GPC total into 2 or 3 doses per day. For example, 1,200 mg would be taken 400 mg at a time. Side Effects Alpha GPC is produced naturally in your body. So is considered well-tolerated and safe. Side effects are rare but can include fatigue, headaches, nervousness, nausea, diarrhea and gastrointestinal issues. This is often an indication you have too much choline in your body. Because Alpha GPC causes an energy boost in many neurohackers, avoid dosing in the evening. Or you may find difficulty getting to sleep. Available Forms Because Alpha GPC tends to liquefy at 99-100%, many suppliers offer 50% Alpha GPC powder combined with 50% of a filler like silicon dioxide. Adjust your dosage accordingly. Alpha GPC is made from soy or sunflower lecithin. So if you’re trying to avoid soy in your diet look for Alpha-GPC “no soy” or labeled as derived from sunflower lecithin. Nootropics Expert® Recommendation Alpha GPC 400 – 1,200 mg per day I recommend using Alpha GPC as a nootropic supplement. Your body does make some Alpha GPC on its own. And from the food you eat. But studies have shown we don’t get an adequate supply of choline from food sources in our modern diet. Alpha GPC is especially helpful for those suffering from age-related cognitive decline. Studies show it helps stop or reverse brain degeneration with Alzheimer’s Disease, and other cognitive disorders. Particularly in the early to mid-stages of the disease.

I suggest starting with a dose of 400 mg daily. And Alpha GPC is a great compliment to a stack including any nootropic from the racetam-family. Anything that causes an increase in uptake of acetylcholine in your brain. You need to provide your brain with the choline it is demanding. Or it starts cannibalizing your own brain cells for more choline. Signs that your lacking adequate choline are headaches. Use Alpha GPC at a ratio of 1:4. For example, 400 mg of Alpha GPC to 1,600 mg of a racetam like Piracetam. Age-related cognitive disorders like Alzheimer’s may want to up the dose to 1,200 mg per day.

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Alpha-Lipoic Acid Alpha-Lipoic Acid has been shown to boost acetylcholine, improve cognition and memory, and is a powerful antioxidant Alpha-Lipoic Acid (ALA) is a sulfur-containing fatty acid naturally found in your body. Lipoic acid is unique among other antioxidants because it is both water- and fat-soluble. You get small amounts of lipoic acid in your diet from spinach and collard greens, broccoli, beef and organ meats. But lipoic acid declines in your body as you age. So you need to supplement with Alpha-Lipoic Acid to achieve the levels your body needs to run optimally. And because Alpha-Lipoic Acid (ALA) is both water- and fat-soluble, it works in all parts of the human cell. The more lipoic acid you have in your system; the more antioxidant benefits you experience. You need alpha-lipoic acid’s antioxidant power. Because it regenerates other antioxidants that were depleted by the ongoing fight with free radicals in your cells. It allows you to use the antioxidants Vitamin C & E, glutathione and CoQ10 already in your body over and over again. In fact, alpha-lipoic acid is so efficient at what it does, it boosts the energy in your cells while reducing inflammation, and getting rid of heavy metals. In your brain, alpha-lipoic acid boosts the production of the neurotransmitter acetylcholine. And even increases glucose uptake in brain cells. Providing you with a boost of mental energy. Alpha-Lipoic Acid is used throughout your body. It helps increase insulin sensitivity which reduces the threat of diabetes. And ALA reduces the chances of metabolic syndrome which is associated with cardiovascular disease, diabetes and weight gain. Alpha-Lipoic Acid vs. S-Lipoic Acid vs. R-Lipoic Acid Lipoic Acid is also known as Alpha-Lipoic Acid, ALA and Thioctic acid. The Alpha-Lipoic Acid you get as a supplement is usually a 50/50 mixture of R-(natural) and S-(unnatural) enantiomers. They are mirror images of each other and called a ‘racemic’ mixture. Most commercially available forms of Alpha-Lipoic Acid include the ‘S-form’, or unnatural form of lipoic acid. Chemically synthesized in 1952, and not found in nature. It is thought that the two enantiomers differ biologically. But much of the research done over the last 30 years has been with the racemic version of Alpha-Lipoic Acid because the R-form was not commercially available. S-Lipoic Acid (the enantiomer not found in nature) may not produce the most essential properties of Lipoic Acid. Including interactions with proteins, enzymes and genes.

R-Lipoic Acid is the form of lipoic acid occurring naturally in the human body, animals, and plants. This is the only form that functions as a co-factor for mitochondrial enzymes involved in energy production. Be aware that most commercially available forms of Alpha-Lipoic Acid include both S- and R-forms of lipoic acid. Alpha-Lipoic Acid is produced as a mixture because R-Lipoic Acid, when separated from the S-form, is very unstable. And deteriorates very quickly. Making it unusable as a dietary supplement. Very few companies go through the complicated, expensive process required to remove the synthetic SALA from R-ALA. So unless the bottle specifically states 100% R-ALA, you’re getting a 50/50 blend. Know that R-ALA may be up to 12 times more effective than S-ALA. How does Alpha-Lipoic Acid Work in the Brain? Alpha-Lipoic Acid boosts brain health and function in several ways. But two in particular stand out. 1. Alpha-Lipoic Acid boosts acetylcholine, a neurotransmitter tied to memory and overall brain function. ALA increases acetylcholine production by activation of choline acetyltransferase and increases glucose uptake. This process supplies more Acetyl-CoA for the production of acetylcholine.42 2. Alpha-Lipoic Acid is a promising weapon in the fight against neurodegenerative diseases like Alzheimer’s. Oxidative stress plays a key role in cognitive disorders because neurons are highly vulnerable to free radical damage. A recent study showed that lipoic acid may help slow down the progression of Alzheimer’s Disease. An area where no known cure has been produced by the big pharmaceutical companies. In this study, 43 patients with dementia were given 600 mg of Alpha-Lipoic Acid daily for 4 years. Researchers concluded from this study, “alpha-lipoic acid might be a successful ‘neuroprotective’ therapy option for Alzheimer’s disease.”43 How things go bad As we get older, our brain chemistry and metabolism changes. ↓ Acetylcholine levels decline ↓ Oxidative (free radical) damage in neural cells ↓ Heavy metal accumulation in cells All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s, Parkinson’s and dementia.

But even if you’re not concerned with the effects of aging, Alpha-Lipoic Acid can help. Alpha-Lipoic Acid benefits Research from hundreds of studies have shown that Alpha-Lipoic Acid will: • • • •

Increase the production of acetylcholine Improve memory and learning ability Restore the health of neurons Boost cognitive performance and memory in Alzheimer’s patients.

Alpha-Lipoic Acid is both water- and fat-soluble and quickly crosses the blood-brain barrier after you take it. ALA improves your brain function and learning processes by directly increasing the production of acetylcholine. Alpha-Lipoic Acid also helps regenerate depleted antioxidants in your system including Vitamins C and E, glutathione and Coenzyme Q10. By reducing inflammation and heavy metals in your brain, you boost cognitive processes and fluid thinking. How does Alpha-Lipoic Acid feel? You may not feel ALA... unless you’re diabetic or have Alzheimer’s. Within these specific groups, Alpha-Lipoic Acid helps with nerve pain, memory, recall and mental performance. Alpha-Lipoic Acid’s provides brain support because it has the ability to boost acetylcholine. So should boost cognition in all age and gender groups. Your entire body, even your DNA is under endless assault. This assault is caused by everything from poor diet to pollution. And your brain cells are getting hit by free radicals thousands of times per day. This oxidation is damaging your cells. Antioxidants fight back against free radicals. When you supplement with Alpha-Lipoic Acid, not only are you using arguably the most effective free radical scavenger on the planet. You’re regenerating antioxidants like Vitamin C & E, glutathione and CoQ10.44 And they join the fight against free radicals alongside Alpha-Lipoic Acid. The Research Alpha-Lipoic Acid plays an essential role in mitochondria. The heart of energy-generation in the human cell. Scientists at Emory University School of Medicine found ALA can stimulate telomerase, the enzyme that lengthens telomeres. The effects of many chronic diseases can be traced back to telomere shortening. (Telomeres are the ‘caps’ on the end of each chromosome in your DNA).

Any treatment that can restore healthy telomeres has great potential in the fight against chronic disease. In this study scientists showed Alpha-Lipoic Acid boosted the production of PGC1-alpha. The telomerase that lengthens telomeres. And they did it in just one day of treatment.45 Alpha-Lipoic Acid reduces wrinkles A topical solution of 5% Alpha-Lipoic Acid was applied to the faces of volunteers. This double-blind, placebo-controlled trial showed a reduction in facial lines, almost complete eradication of fine lines, and an overall improvement of skin color and texture in most volunteers.46 Alpha-Lipoic Acid critical for cellular energy Cellular energy is behind every single action that happens in your body. Including your brain. Cellular energy is required for muscle movement, producing new cells, wound healing and thinking. The mitochondria in each of your cells is the source of this energy. This ongoing energy production process is call the Krebs Cycle. Alpha-Lipoic Acid is a cofactor to two key enzymatic reactions within the Krebs Cycle. In the simplest terms, without ALA, cellular energy is not possible. And without cellular energy, well… life is not possible.47 Memory loss reversed with ALA and ALCAR Accumulated oxidative damage to brain cell mitochondria eventually leads to neuronal and cognitive dysfunction. One study on rats showed supplementing with ALCAR and Alpha-Lipoic Acid improved memory. By lowering oxidative damage and improving mitochondrial function.48 Dosage Notes Taking Alpha-Lipoic Acid with a meal decreases its bioavailability. So I recommend taking ALA on an empty stomach (1 hour before eating). Most Alpha-Lipoic Acid supplements contain a 50/50 mixture of R-LA and S-LA. Supplements claiming to contain only R-LA are often more expensive. And information regarding their purity is not often available. Peak plasma (blood) concentrations of R-LA were found to be 40-50% higher than S-LA. This suggests that R-LA is better absorbed than S-LA.49 • • •

Alpha-Lipoic Acid dosage for cognitive benefit is 2- 600 mg per day. ALA dosage for diabetic neuropathy is 800 mg per day divided into two doses. Alpha-Lipoic Acid dosing for antioxidant benefit is 50 – 100 mg per day.

Side Effects Side effects from using Alpha-Lipoic Acid as a supplement are generally rare. But can include diarrhea,

fatigue, insomnia and skin rash. Alpha-Lipoic Acid can lower blood sugar levels. So if you have diabetes or low blood sugar, you should take Alpha-Lipoic Acid under the supervision of your doctor. Alpha-Lipoic Acid supplementation can lower levels of thyroid hormone. So get your thyroid labs done when using ALA. And adjust your dosage of both ALA and thyroid meds accordingly. Alpha-Lipoic Acid can lower levels of Vitamin B1 (Thiamine). This can be dangerous for alcoholics, or in cases of malnutrition. It would be wise to add Vitamin B1 or Sulbutiamine if you’re taking ALA. The chemical structure of Biotin is similar to that Alpha-Lipoic Acid. And there is some evidence that ALA can compete with Biotin for transport across cell membranes. This may require higher doses of Biotin when you’re using ALA. Available Forms Most Alpha-Lipoic Acid available as a supplement is a 50/50 combination of R-LA and S-LA. S-LA is the synthetic version of ALA and not found in nature. R-LA and S-LA are combined because R-LA is highly unstable on its own. And degenerates quickly. Studies have shown that 30-40% of an oral dose of Alpha-Lipoic Acid is absorbed. Oral ALA supplements are better absorbed on an empty stomach. Taking ALA with food reduces total plasma (blood) concentrations by about 30%. The sodium salt version of R-LA may be better absorbed than free lipoic acid, likely because of its higher solubility.50 There is little evidence whether R-LA supplements are more effective than regular Alpha-Lipoic Acid supplements in humans. Nootropics Expert® Recommendation Alpha-Lipoic Acid 50 – 600 mg per day. I recommend using Alpha-Lipoic Acid as a nootropic supplement. Your body does make some Alpha-Lipoic Acid on its own. And from the food you eat. But the science is clear that supplemental ALA is a potent antioxidant. And acetylcholine booster. Alpha-Lipoic Acid can lengthen telomeres which is great for your neurons. And neurogenesis (new neuron creation). ALA also helps regenerate antioxidants already in your system that have been depleted while doing their job. And it helps get rid of free radicals in your cells. So you get a double benefit when using Alpha-Lipoic Acid as an antioxidant. Alpha-Lipoic Acid also helps in the creation of acetylcholine. Which boosts all cognitive functions

including memory, recall, focus and concentration. ALA is especially helpful for those suffering with diabetes. Studies show it helps relieve diabetic neuropathy or nerve pain. But care must be taken because ALA can lower blood sugar levels. So work with your doctor when using Alpha-Lipoic Acid. I suggest starting with a dose of 400 mg daily. And work your way up to 600 mg per day. Taken in two doses during the day. Alpha-Lipoic Acid is often stacked with B-vitamins.

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Aniracetam Aniracetam has been shown to relieve depression, boost learning & memory, improve verbal fluidity, increase music listening pleasure, and make you more social Aniracetam (1-p-anisoyl-2-pyrrolidinone) is a fat-soluble ampakine nootropic in the racetam-class of compounds. AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic) refers to one of three glutamate receptors in your brain.51 The racetam-class of nootropics have a pyrrolidone nucleus at their core. And Aniracetam is a Cholinergic compound, meaning it affects acetylcholine levels in the brain. Aniracetam is up to 10-times more potent than the original racetam, Piracetam. It was patented by Swiss-based pharmaceutical company F. Hoffmann-La Roche AG in the 1978. Aniracetam is sold as a prescription drug (Ampamet, Draganon, Memodrin, Referan, Sarpul) in Europe. It is sold as an over-the-counter, unrestricted compound in the United States. But not as a dietary supplement. A favorite racetam among the nootropics community. Neurohackers use Aniracetam to boost memory and learning. And to relieve anxiety, depression, stress, and improve sociability.52 One of the original synthetic nootropic compounds, it is known as a cognitive enhancer. And is known for its anxiolytic, or anti-anxiety effects. As an ampakine nootropic, Aniracetam helps increase attention span, alertness and boosts memory. Ampakines tend to have a stimulant effect. But do not produce the same stimulant side effects as Ritalin or coffee from prolonged use. Aniracetam vs. Piracetam: What’s the Difference? Swiss-based pharmaceutical company F. Hoffmann-La Roche AG developed Aniracetam in the late 1970’s as a derivative of Piracetam. Aniracetam is fat-soluble while Piracetam is water-soluble. Fat-soluble molecules cross the bloodbrain barrier more easily than water-soluble molecules. Aniracetam works faster in the brain after taking compared to Piracetam because of its superior bioavailability. But its effects don’t last as long as Piracetam. The potency of Aniracetam seems almost counter-intuitive. Because most of an Aniracetam dose is lost in the liver during digestion. Only 0.2% of the original dose is available to the brain.53 Piracetam is nearly 100% bioavailable.54 Both Aniracetam and Piracetam are cognitive enhancers. And both have neuroprotective qualities. Both racetams are able to improve learning and memory. And both are able to repair brain damage.

Aniracetam has additional benefits not shared with Piracetam. Aniracetam can reduce anxiety, depression and fear. And increase sociability.55 This may indicate its effects on dopamine and serotonin receptors in the brain. How does Aniracetam Work in the Brain? Aniracetam boosts brain health and function in several ways. But two in particular stand out. 1. Aniracetam modulates AMPA receptors in the brain. The main metabolite of Aniracetam (7080%) is N-anisoyl-GABA and is responsible for many of its effects. 2-Pyrrolidinone and p-anisilic acid are additional metabolites of the drug (20-30%), both of which are also active.56 The main function of these metabolites is on the glutamate system in the brain. It desensitizes the glutamate receptors. This causes the neurotransmitter glutamate to become more available in the brain. More glutamate means better cognition and memory. And neural protection and repair due to brain injury. 2. Aniracetam also seems to affect dopamine and serotonin receptors in the brain. Leading to improved mood and sociability. One study published in the European Journal of Pharmacology demonstrated the anti-anxiety effects of Aniracetam. Researchers tracked the brain pathways in mice showing Aniracetam’s mechanism of action.57 Illustrating the effect on dopamine and serotonin. How things go bad Glutamate is an excitatory relative of GABA. While GABA has a calming effect, glutamate stimulates. Glutamate is the most common neurotransmitter in the central nervous system. But glutamate is actually toxic to neurons. And too much of it in your brain can kill brain cells. Lou Gehrig’s Disease for example, is caused by excess glutamate. But glutamate is a pivotal neurotransmitter in the brain. It links the brain circuits involved in memory, learning and perception. ↑ Too much glutamate can kill neurons ↓ Too little glutamate can cause problems with memory, learning and perception ↓ Acetylcholine levels decline All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Aniracetam can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting acetylcholine and controlling glutamate in the brain.

Aniracetam benefits Aniracetam modulates AMPA receptors which are involved in how glutamate is used in your brain. More of the neurotransmitter glutamate is available. Which means better neural signaling across synapses. Your brain is working optimally despite stress, fatigue and anxiety. There is anecdotal evidence that Aniracetam boosts communication between left and right brain hemispheres. You become more creative. And are prone to making innovative and resourceful decisions. Aniracetam combined with choline boosts the production of the crucial neurotransmitter acetylcholine. Improving memory, recall and focus. Aniracetam is fat-soluble and quickly enters your brain after you take it. Once in your brain, it boosts signal transmission, and protects neurons. Aniracetam boosts acetylcholine so you should add a good choline source. Try Alpha GPC or CDPCholine with Aniracetam. And give your brain the choline it needs. How does Aniracetam feel? Nootropics users report: •

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Aniracetam as a study aid. On its own, Aniracetam seems to increase attention span for many neurohackers. And when combined with caffeine, many report being able to work effortlessly for hours on end. Increased auditory perception. If you love music, Aniracetam can take you deeper into your listening experience. Minute details like background guitars, and other auditory effects come alive. Every instrument becomes part of the sound stage. Increased visual acuity. The visual effects of Aniracetam feel like your brain is processing a broader spectrum of what’s in your visual range. Nature and your surroundings look more vibrant and beautiful. Sociability. Many users report being able to articulate thoughts, and improved speaking ability. Language and your vocabulary seem to flow effortlessly. Thoughts and ideas come with less effort.

You should be able to experience the effects of Aniracetam soon after you take it. It’s fat-soluble so it’s digested and enters your cells quickly. And unlike other stimulants, there is no “crash” once Aniracetam leaves your system. The Research Researchers worked with 276 patients with cognitive disorders. They were given Aniracetam and tested at 3, 6 and 12 months. Improved emotional states and better motor functionality was observed within 3 months. A boost in cognitive performance was observed within 6 months.

Findings concluded Aniracetam “is a promising option for patients with cognitive deficit” disorders. Improvements held throughout the 12-month study. And there was a favorable effect on emotional stability in patients with dementia.58 Aniracetam as an antidepressant A study published in Psychopharmacology in 2001 showed Aniracetam helped stimulate the release of dopamine. The study reported Aniracetam as effective against depression caused by age-related brain dysfunction.59 Aniracetam improves learning & memory Researchers put rats and mice through six scenarios. From drug-induced memory loss to electric shock avoidance, while administering Aniracetam. The results of all tests conclusively showed Aniracetam improving cognitive function. It didn’t matter what they put these animals through. Learning and memory improved with the use of Aniracetam.60 Aniracetam repairs Fetal Alcohol Syndrome We’re exposed to toxins everywhere we go. And in everything we do during our day. This toxin exposure wreaks havoc in our body, including our brain. In this study, scientists showed one way to repair damage to synaptic transmission in the brain. They exposed pregnant Sprague-Dawley rats to ethanol and a saccharin-like sweetener. Pups born to these female rats would normally be extremely cognitively impaired. Just like babies born to alcoholic mothers. In this study, the pups born with fetal alcohol syndrome were treated with Aniracetam 18 and 27 days after birth. Aniracetam completely restored synaptic transmission in their brains. And reversed any cognitive deficits associated with fetal alcohol syndrome.61 Dosage Notes Recommended Aniracetam dosage is 1,500 mg per day. Taken in two 750 mg doses. One Aniracetam dose in the morning, and one in the early afternoon. Aniracetam is sold in tablet, capsule and powder form. Tablets and capsules are usually 750 mg each. Since Aniracetam is a fat-soluble nootropic, you should take it with a meal containing healthy fats. Or with a tablespoon of extra virgin, expeller cold-pressed coconut or olive oil. Or other similar healthy fat to ensure quick absorption. Side Effects Aniracetam non-toxic. So is considered well-tolerated and safe. Side effects are rare but can include anxiety, fatigue, headaches, nervousness and nausea. Side effects are often a result of unusually high doses of the nootropic. Headaches from using Aniracetam typically happen when you forget to combine it with a good choline

supplement. Headaches are often a symptom of a choline deficit in your brain. Available Forms Aniracetam is sold in tablet, capsule and powder form. Tablets and capsules are usually 750 mg each. In Europe and some other countries around the world, Aniracetam is a prescription drug. And sold under the brand names Ampamet, Draganon, Memodrin, Referan, and Sarpul. Nootropics Expert® Recommendation Aniracetam 1,500 mg per day I recommend using Aniracetam as a nootropic supplement. Your body does not make Aniracetam on its own. So to get its benefits you must take it as a supplement. Aniracetam is especially helpful for those suffering from depression. Studies show it helps stop and reverse the symptoms associated with depression. This nootropic helps boost the activity of dopamine and serotonin in your brain. Personally, I’ve found Aniracetam to be more effective (and safer) than any prescription anti-depressant I’ve ever tried. Aniracetam is also particularly useful to students and executives who want to boost cognition, learning and memory. My experience using Aniracetam shows it helps boost study scores, work flow, learning and memory. Aniracetam also helps improve verbal fluidity and sociability. Words seem to come easily, and vocabulary you didn’t know you had access to come into play. Music sounds richer and fuller, and your listening experience enters a new level of music appreciation. You should use Aniracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain. You can safely boost daily intake of Aniracetam to 3,000 mg. if needed.

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Artichoke Extract (Luteolin) Artichoke Extract (Luteolin) has been shown to boost memory and learning, improve motivation and mood, and stimulate the growth of new neurons in the brain. Artichoke Extract (Luteolin) contains a naturally occurring compound called luteolin. Luteolin is a natural and powerful phosphodiesterase (PDE4) inhibitor. Excess PDE4 in your brain is bad news because it degrades cAMP. Cyclic adenosine monophosphate (cAMP) is a derivative of adenosine triphosphate (ATP). ATP is synthesized within mitochondria in each of your cells. cAMP is part of that cellular energy source. As a secondary messenger in neurons, cAMP helps produce proteins for increased neuron growth. Neuron dendrites connect to other neurons through a process called Long-Term Potentiation (LTP). LTP creates an increase in the production of cAMP. Which triggers a biochemical cascade of reactions. Which is the basis of learning and memory. When cAMP is degraded, it interferes with efficient brain signaling. And interferes with Long-Term Potentiation. Making it harder to develop memories, and to learn. Artichoke Extract (luteolin) reduces PDE4. When PDE4 is reduced, you not only maintain healthy cAMP cellular energy. Brain signaling is actually amplified.62 When luteolin is combined with another natural herb called Forskolin, you get double duty. Luteolin reduces PDE4 which maintains cellular signal strength. And Forskolin boosts cAMP. Increasing brain signal strength. Artichoke Extract (Luteolin) vs. Pure Luteolin: What’s the Difference? Luteolin is not bioavailable on its own if taken as a supplement.63 It requires the presence of other naturally occurring bioflavonoids to be metabolized by your body. And to reach the cells in active form. Artichoke Extract contains the compounds apigenin-7-rutinoside and narirutin, which unlocks Luteolin’s potential to work in your cells.64 How does Artichoke Extract (Luteolin) Work in the Brain? Artichoke Extract (Luteolin) boosts brain health and functions in several ways. But two in particular stand out. 1. Artichoke Extract (luteolin) inhibits PDE4 which boosts cAMP activity in brain cells. cAMP helps stimulate the production of CREB (cAMP response element-binding protein). An increase in CREB enhances Long-Term Potentiation (LTP). LTP is the connection between brain synapses. Strengthening in response to stimulation by neurons on either side. A major component in both learning and memory.

Memories are stored at a cellular level. And retrieved at a cellular level. This well-travelled pathway is strengthened by boosting cAMP with Artichoke Extract (Luteolin). This improvement in memory was demonstrated by researchers at the University of Genoa in Italy. Rats and mice were used in this study. In this case, the PDE4 inhibitor they used was a chemical derivative of rolipram. (Rolipram cannot be used in human patients because it causes vomiting). Results of the study showed this derivative enhanced memory function even at low doses. Acting on the same neural pathways as Artichoke Extract in humans.65 2. Artichoke Extract (Luteolin) reduces brain inflammation. Researchers studied the effect of Luteolin on immune system cells in the brain called microglia. Microglia produce cytokines in response to infections and toxins. Over-production of cytokines result in inflammation and the destruction of neurons. In this study, brain cells in mice were pretreated with Luteolin before being exposed to a substance that induced inflammation in brain cells. The same type of inflammation humans experience from daily exposure to toxins. The study showed that Luteolin offered protection against brain inflammation. And its consequences. Including problems with cognition and memory. The research team concluded that Luteolin “may be useful for mitigating neural inflammation”.66 How things go bad Environmental factors, ADHD, illness, stress and aging changes our brain chemistry. ↓ Mood and motivation declines ↓ Memory and recall declines ↓ Long-term memory fades All of these changes are contributing factors to poor quality of life. And as they progress, to neurodegenerative diseases like Alzheimer’s, dementia and Parkinson’s. Artichoke Extract (Luteolin) benefits Research from hundreds of studies, and feedback from neurohackers have shown that Artichoke Extract can: • • •

Improve memory by inhibiting PDE4 in the brain (which boosts cAMP activity) Boost dopamine levels in the brain Tame inflammation in the brain

Artichoke Extract (Luteolin) is water-soluble and quickly enters your brain after you take it. Once in your brain, it inhibits PDE4 which boosts cAMP activity. cAMP is involved in the Long-Term

Potentiation process of preserving memories. Artichoke Extract combined with Forskolin is even more effective. Because not only are you helping cAMP activity in the brain, you’re boosting cAMP with Forskolin. Inhibiting PDE4 and boosting cAMP also makes the effect of normal dopamine production more effective. Boosting processes in this stream of chemical reactions in the brain increases learning and memory.67 Without the side effects of stimulating dopamine production through the use of drugs like Adderall or Ritalin. How does Artichoke Extract (Luteolin) feel? Many neurohackers report that Artichoke Extract with Forskolin improves mood. It motivates you to want to learn, and to get things done. Some say it works as good as Modafinil. The general consensus is: • • • •

Improved mood and motivation Increased ability to study Increased ability to retain information Improved long-term memory

The Research Microglia cells are immune cells in your brain and spinal cord. They produce signaling molecules called cytokines. These cytokines are cell signaling molecules that aid communication between cells in immune responses. When microglial cells are not regulated, they produce excessive levels of cytokines. And inflammatory cytokines kill neurons. Leading to cognitive aging and neurodegenerative diseases like Alzheimer’s. And are responsible for producing symptoms like sleepiness, loss of appetite, memory deficits and depression. Researchers at the University of Illinois at Urbana–Champaign worked with a group of young, and older mice. The mice were fed a control diet, or a luteolin-supplemented diet for 4 weeks. The research team found that luteolin helped regulate microglial cells. And stopped them from producing excess cytokines. This reduced inflammation in the brains of aged mice. And restored memory to levels observed in younger mice.68 Artichoke Extract improves mood Users report that Artichoke Extract boosts mood. Researchers at Kurume University School of Medicine in Japan demonstrated in the lab how this boost in mood occurs. When dopamine D1 receptors in the prefrontal cortex of the brain malfunction, psychotic symptoms and other nasty symptoms show up. Including schizophrenia. The study group found that dopamine D1 receptors signal through the cAMP cascade. Which is

modulated by PDE4 enzymes. In this study, researchers inhibited PDE4 production in the lab. Showing that an increase in dopamine resulted in influencing cognitive function. Proving the antipsychotic action of suppressing PDE4.69 Artichoke Extract improves memory Researchers at the West Virginia University Health Sciences Center in the USA worked with tame and wild-type mice. Suppressing PDE4 in the mice enhanced memory. And increased the growth of new neurons in the hippocampus of the brains in these mice.70 Dosage Notes For PDE4 suppression: 900 mg Artichoke Extract per day For boosting cAMP: 4 mg Forskolin (Coleus forskohlii) extract per day Note: Check the label of the Forskolin supplement for the amount of actual Forskolin in each capsule. For example, 385 mg of Forskohlii may only be guaranteed to contain 3.85 – 4 mg of actual Forskolin. Which is what you need. Also note that more Forskolin is not better as it causes a strong fatigue effect at higher doses. For counteracting Forskolin’s effect on Acetylcholinesterase: add 800 mg Acetyl-L-Carnitine (ALCAR) – (200 mg of ALCAR for every 1 mg of Forskolin) per day Many users of this stack report it helpful to supplement with 500 mg Phenylalanine, a B-Vitamin Complex and caffeine (coffee or preferably green tea). Note: the above combination of nootropics is known among neurohackers as the CILTEP stack. CILTEP stands for Chemically Induced Long-Term Potentation. Side Effects Acetylcholinesterase is upregulated by cAMP which makes you sleepy. This means that available Acetylcholine in your brain drops. You can counteract this with Acetyl-l-Carnitine (ALCAR), which calms the upregulation of Acetylcholinesterase. Artichoke extracts have been documented to lower blood cholesterol in human and animal studies. This means it may potentiate the effects of cholesterol-lowering and statin drugs. Artichoke Extract affects the liver by stimulating the flow of bile. So if you have liver disease be careful about using this herb. Artichoke Extract can also cause gallbladder contractions. So if you have gallbladder disease or gallstones, check with doctor before taking this herb. Available Forms Two very different forms of artichoke are available. The Globe Artichoke (Cynara cardunculus) which has been cultivated and used since ancient times. And the Jerusalem Artichoke (Helianthus tuberosus)

which is from the Northeastern USA. All references to Artichoke Extract in this article is for the Globe Artichoke. Users report that Artichoke Extract (Standardized to 5% Cynarins) of most premium brains are helpful in reducing PDE4. Nootropics Expert® Recommendation Artichoke Extract (Luteolin) 900 mg per day I recommend using Artichoke Extract as a nootropic supplement. Your body does not make Artichoke Extract (Luteolin) on its own. So you must take it as a standardized supplement. Luteolin on its own as a supplement does not appear to be effective. Luteolin is not bioavailable so your body can’t use it. Luteolin as part of the Artichoke plant is used by your body. Because it contains other flavonoids that help your body absorb it. Artichoke Extract is especially helpful when combined with Forskolin. It helps boost memory, increases motivation and the desire to learn. And helps improve mood. I suggest dosing Artichoke Extract at 900 mg per day taken in the morning. With 4 mg of Forskolin. Stack this with 800 mg of ALCAR to keep your acetylcholine levels up. I’ve also found that combining this Artichoke Extract stack with caffeine is helpful. The L-Theanine in green tea works with the caffeine boost we need. Without the side effects of coffee. I’ve also found that more in not better with this stack. And taking it early in the day is good for a productive day. The effects last all day. And finally, we are making the effects of normal dopamine function more effective with this stack. It triggers the desirable downstream processes that increase learning and memory. The chemical dynamics of the dopamine system are preserved. And we don’t get the negative side effects of using a stimulant like Adderall or Ritalin. This Artichoke Extract (Luteolin) stack increases mental endurance for encoding long-term memories.

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Ashwagandha Ashwagandha has been shown to repair and reverse damage to the brain caused by chronic anxiety and stress Ashwagandha (Withania somnifera) is one of the most powerful herbs in Ayurvedic healing. This ancient herbal remedy has remarkable anti-depressant qualities. And has been shown to be as good as many prescription pharmaceuticals in treating depression and anxiety. In Sanskrit, Ashwagandha means “smell of horse”. Meaning this herb imparts the strength and vigor of a stallion. Ashwagandha is often referred to as “Indian ginseng” because of its rejuvenating properties. But botanically, Ashwagandha and ginseng are unrelated. Native to India, Pakistan and Sri Lanka. Ashwagandha is now being grown in other regions including the United States. Ashwagandha is in the same family as the tomato. It’s a small woody shrub with oval leaves, and fivepetal yellow flowers. The fruit is red and the size of a raisin. The plant is also known as the “Winter Cherry”. Ashwagandha is known as an adaptogen. Which means it helps your body adapt to stress, both mental and physical. The Indian Materia Medica lists Ashwagandha for: • • • • • • •

general debility impotence general aphrodisiac purposes brain fatigue low sperm count nervous exhaustion where general vigor must be restored.

Ashwagandha extract has been shown to be an effective antioxidant in the brain. Clearing the cellular waste implicated in Alzheimer’s Disease.71 Is also boosts memory and cognition. By reducing stress and increasing acetylcholine. And regeneration of nerve networks in the brain. How does Ashwagandha Work in the Brain? Ashwagandha boosts brain health and function in several ways. But two in particular stand out. 1. Ashwagandha enhances GABA receptors and serotonin in the brain. It appears to work on neuron receptors, enabling GABA to connect easier. This inhibits the signals present under a stress

response in the brain. Anxiety goes down. A study was conducted at The Canadian College of Naturopathic Medicine with 75 volunteers with moderate to severe anxiety. Ashwagandha produced a significant decrease in anxiety levels over the control group.72 2. Ashwagandha improves cognitive and psychomotor performance in a healthy brain. Researchers at Nizam’s Institute of Medical Sciences in Hyderabad, India worked with 20 healthy male volunteers. In this double-blind, placebo-controlled trial participants were given 250 mg capsules of standardized Ashwagandha extract daily for 14 days. Significant improvements in reaction times were reported at the end of the trial. The study suggests that Ashwagandha extract improves cognitive and psychomotor (physical reaction) performance even when you’re in the best of health.73 How things go bad Chronic stress and cortisol can damage your brain. Neuroscientists at the University of California, Berkeley, found that chronic stress triggers long-term changes in brain structure and function.74 Chronic stress changes neural networks. Cortisol creates a domino effect that hard-wires pathways between the hippocampus and amygdala. (The amygdala (lizard brain) is the area responsible for your fight-or-flight response). This hard-wiring caused by stress is not the way the brain was designed. But chronic, ongoing stress tricks the brain into rebuilding circuits and hunkering down for the long haul. This re-wiring appears to be permanent. Unless you intervene with something like Ashwagandha. Chronic stress seems to ‘flip a switch’ in stem cells in the brain. And turns them into a type of cell that prevents connections to the prefrontal cortex. Preventing improved learning and memory. And laying down the scaffolding linked to anxiety, depression and PTSD (Post Traumatic Stress Disorder). ↓ Chronic stress unnaturally coats neurons in myelin ↓ Chronic stress reduces the number of neurons ↓ Gray matter decreases and white matter increases. Under conditions of chronic stress and excess cortisol, your brain’s neurons are coated (or sheathed) in myelin. Under healthy conditions this “sheathing” is a protective measure. But this excessive sheathing is likely an evolutionary measure made to reinforce the connection between the hippocampus and amygdala. Improving the fight-or-flight response during extended periods of threat or attack.

In the modern world, chronic stress hijacks your fight-or-flight response system. It backfires in daily life in when you are not typically in physical danger. Ashwagandha benefits Ashwagandha undoes damage to the brain caused by chronic stress. And helps keep it healthy. Ashwagandha improves cognitive function. Glycowithanolides, one of the many compounds found in this herb, reduce cortisol. And overall energy levels are enhanced through optimizing mitochondrial function. It also has GABA-mimicking effects in the brain. Comparable to the effects of prescription benzodiazepines like lorazepam (Ativan). Ashwagandha can also help prevent and repair damage caused by Alzheimer’s, Parkinson’s and Huntington’s disease. Through its antioxidant and inflammation-reducing mechanisms. Ashwagandha even provides protection and regeneration of neurons during opiate and heroin withdrawal. And eases withdrawal symptoms. In Ayurvedic medicine, Rasayana herbs are used to promote a youthful state of physical and mental health. The ancients considered Medhya Rasayana herbs to be working with higher brain function. These are mind-rejuvenating herbs. Of the 8 or 9 most cherished herbal remedies, Ashwagandha is the highest or most prominent of Ayurvedic Rasayana herbs. Acting as an adaptogen, rejuvenating the nervous system, and boosting the body’s resilience to stress. How does Ashwagandha feel? Ashwagandha users report: •

Ashwagandha as a stress-reliever. If you are experiencing severe fatigue and brain fog, it’s likely stress. Chronic or severe stress can disguise itself in many ways. Including feeling abnormally fatigued. You find that you are not sleeping well. Or don’t feel rested and refreshed when waking up in the morning. Even after taking a sleeping pill. Many report a rapid change in energy and motivation as soon as they take Ashwagandha. Others won’t feel the effects for a couple of weeks before relief sets in. You’ll know Ashwagandha is working when you wake up in the morning feeling refreshed. And eagerly looking forward to starting your day.

•

Ashwagandha as an anti-anxiety aid. As an anti-anxiety aid users say they feel their selfconfidence has been restored. Your speech will feel more fluid and easier, especially in public settings. No more panic attacks.

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Ashwagandha as an anti-depressant. Depression, even if it’s not professionally diagnosed, can destroy your life. Ashwagandha users say it is the best anti-depressant they’ve ever used. Their energy is restored, motivation is back, and they’re able to focus.

Ashwagandha works on many levels in the brain. Cortisol levels are stabilized. And the damage to your brain begins to correct itself. Acetylcholine levels rise so you’re able to think clearly again. Neurons get repaired, and cognition and memory return to levels you experienced when you were younger. And GABA receptors are re-activated producing a calming effect. The Research Researchers at Asha Hospital in Hyderabad, India did a double-blind, randomized, placebo-controlled trial with 64 subjects who had a history of chronic stress. The study group took a 300 mg capsule of full-spectrum Ashwagandha root twice a day for 60 days. Follow up calls to participants were done on the 15th, 30th, 45th and 60th day of the trial. Researchers reported serum cortisol levels were substantially reduced. The report concluded “that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual’s resistance towards stress and thereby improves self-assessed quality of life”.75 Ashwagandha as a nootropic One study done in a lab in India subjected laboratory mice to electroconvulsive shock treatment. Or were given scopolamine to induce amnesia (memory loss). Both sets of mice were given Ashwagandha extract daily after the shock or chemical treatments. Ashwagandha extract restored their memory and motor skills.76 Ashwagandha as an anti-depressant Scientists did a study on rats to compare Ashwagandha with the popular benzodiazepine antidepressant lorazepam (Ativan). And the tricyclic anti-depressant imipramine (Tofranil). Researchers gave the rats either Ashwagandha, lorazepam or imipramine. 30 minutes later they put the rats through a maze, had them interacting socially, and even forced them to swim. They concluded that as a mood stabilizer, Ashwagandha worked on depression and anxiety as well as either of the two anti-depressants.77 Dosage Notes Ayurvedic Pharmacopoeia of India recommends 3 – 6 grams daily of standard ground Ashwagandha powder. • •

For arthritis: 250 – 500 mg of extract (4-5% withanolides) For antioxidant protection: 100 – 200 mg of extract (4-5% withanolides)

• • • •

For immunity: 100 – 200 mg of extract (4-5% withanolides) For relaxation: 250 – 500 mg of extract (4-5% withanolides) For stress: 250 – 500 mg of extract (4-5% withanolides) For sexual performance: 250 – 500 mg of extract (4-5% withanolides)

For higher does like 500 mg, take 250 mg in the morning and another 250 mg early afternoon. Side Effects Note: Ashwagandha stimulates your thyroid. So if you are hypothyroid, use Ashwagandha with caution. And check with your endocrinologist to be safe. Ashwagandha is non-toxic at moderate doses. If you are pregnant do not use Ashwagandha as it could cause a miscarriage. This herb is an adaptogen with powerful hormonal effects. Ashwagandha can enhance the effects of sedatives, anti-depressant and anti-anxiety medications including St. John’s Wort. It can also interact and possibly amplify the effects of immune suppressants, blood pressure medication, and drugs used to control blood glucose levels. Ashwagandha can boost the effects of alcohol. And do not use Ashwagandha if you have bleeding issues, or before surgery. Other possible side effects include diarrhea, nausea, abdominal pain, drowsiness and slowed pulse. Available Forms Ashwagandha is available as a powder, capsules, tincture and tea. The root and berry of the plant are used. The ground root of the herb is used as the base of an Ashwagandha supplement. Active ingredients of Ashwagandha include alkaloids, saponins, and withanolides. Look for the percentage of active ingredients listed on the bottle or package. Typically, you’ll see something like “standardized to X% of withanolides”. Avoid supplements that list “other ingredients” on the label. And look for Certified Organic to ensure the root used to make your Ashwagandha supplement is free of heavy metals, pesticides and herbicides. Nootropics Expert® Recommendation Ashwagandha Extract 250 – 500 mg per day I recommend using Ashwagandha as a nootropic supplement. Your body does not make Ashwagandha on its own. So to get its benefits you must take it as a supplement. Ashwagandha is especially helpful for those suffering from anxiety and stress. Studies show it helps stop and reverse the devastating effects of stress on your brain, and body. This nootropic helps repair the damage to neurons and synapses caused by chronic stress.

Ashwagandha is a powerful adaptogen. Which means it helps increase the effect of certain hormones when activity is low. And will block excess stimulation when activity is too high. Ashwagandha as an adaptogen helps balance cortisol in the body caused by chronic stress. Chronically elevated cortisol levels suppress immunity, create fat deposits on the belly, face and neck, reduces libido, causes bone loss, causes insulin resistance, and brain fog. Balancing cortisol levels with Ashwagandha improves your sleep quality, immunity, stress response, organ function, reduces fatigue, and brain fog. Ashwagandha is also helpful for those suffering from anxiety and panic disorders. A study published in Phytomedicine showed the calming effect of this herb was equal to the drug Ativan (lorazepam). Without the side effects. You can safely take up to 750 mg of Ashwagandha extract daily if needed. Most get all the benefit they need with 500 mg. Dosed 250 mg in the morning, and another 250 mg early afternoon.

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Bacopa Monnieri Bacopa Monnieri has been shown to boost memory and cognition, improve mood, and reduce stress Bacopa Monnieri (Brahmi) is an aquatic herb originally found in the wetlands and marshy areas of Southeast Asia and India. Bacopa, also known as water hyssop, is often referred to as “Brahmi”. Named after the supreme god Brahma. Ancient Ayurvedic texts talked about Bacopa. It was recommended to devotees to help memorize long passages of text. In the West, Bacopa Monnieri is often used to reduce anxiety, depression and stress. But it’s gaining popularity in the nootropic community as a powerful memory and cognition booster. The active compound Bacoside A in Bacopa easily crosses the blood-brain barrier. How does Bacopa Monnieri Work in the Brain? Bacopa Monnieri boosts brain health and function in several ways. But two in particular stand out. 1. Bacopa Monnieri boosts memory. Bacopa’s two active components are bacosides A and B. They improve the signaling of electrical impulses between neurons in your brain. Bacosides also help rebuild damaged neurons. Bacopa Monnieri helps you learn and remember things more easily. In one study, researchers gave 54 volunteers in Portland, Oregon 300 mg of B. Monnieri per day for 12 weeks. After the 12-week study, the people taking Bacopa had: • • • • •

Better word recall Better attention Better memory scores A great ability to focus while learning Less anxiety and lower heart rates78

2. Bacopa Monnieri reduces stress. Bacopa has traditionally been used in Ayurveda as a tonic for the nervous system. It helps to reduce anxiety. Research at Banaras Hindu University in India showed Bacopa as effective for anxiety as the benzodiazepine drug lorazepam. One of the side effects of lorazepam is memory loss. Bacopa Monnieri on the other hand, reduced anxiety while boosting cognition.79 How things go bad Chronic stress and cortisol can damage your brain. Neuroscientists at the University of California, Berkeley, found that chronic stress triggers long-term change in brain structure and function.80

Chronic stress damages neural networks. Certain proteins are over-expressed damaging neurons as a result. Toxins invade cells, hijacking their normal, healthy function. And oxidative damage by free radicals harm brain cells if they’re not removed. ↓ Chronic stress reduces memory capacity ↓ Toxins kill brain cells from the inside ↓ Free radicals destroy neurons and synapses Under conditions of chronic stress your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition, and decision-making all suffer as a result. Bacopa Monnieri benefits Bacopa Monnieri undoes damage to the brain caused by chronic stress. And helps keep it healthy. This is a little complicated, so stay with me here. Your brain is protected by heat-shock protein 70 (Hsp70), cytochrome enzymes EROD and PROD, and superoxide dismutase (SOD). Hsp70 helps proteins in cells retain normal structure, so they remain functional. EROD (7ethoxyresorufin-O-deethylase) and PROD (7-pentoxyresorufin-O-dealkylase) are detox enzymes. They protect your brain by converting bad toxins into less harmful compounds. And SOD battles destructive free radicals called superoxides. And converts them into harmless organic compounds. Bacopa Monnieri Keeps Your Brain Healthy Under Stress When you are under stress, levels of Hsp70 increase in all regions of your brain. But research shows that animals pretreated with Bacopa for 7 days prevented most of this increase in Hsp70. Particularly in areas of the brain responsible for memory. This means that producing less Hsp70 under stress, Bacopa makes your brain less susceptible to stress. Bacopa kept those regions of the brain in a non-stressed state. Even in the presence of stress. Bacopa also has a preemptive action on EROD, and PROD. Rats treated with Bacopa, but not under stress, saw an increase in these two enzymes. Suggesting that Bacopa helps stockpile these protective enzymes to help you better deal with stress. And when it comes to SOD, researchers said, “Bacopa helps in coping with the combined hypoxic, hypothermic, and immobilization stress, which could lead to an onslaught of free radicals.” So Bacopa helps SOD activity and prepares cells to weather attacks by free radicals.81 Translated, this all means Bacopa helps your brain deal with stress. And helps boost memory. How does Bacopa Monnieri feel?

The effects of Bacopa are not felt immediately. But seem to build over time. Some users report a pronounced anti-anxiety effect within 2 – 4 days of supplementing with Bacopa. In one study done in Australia, results were measured at 5 and 12 weeks of taking Bacopa. The results showed improved speed of information processing, and an increase in learning and memory. Maximum reduction in anxiety was realized after 12 weeks of use.82 Some neurohackers say they feel the effects of Bacopa Monnieri sooner than 4 weeks. And the effects seem to keep working even after stopping supplementation. The effects are long-term. Long term users say they consistently feel calmer, can think quicker and have better memory. The Research Bacopa Monnieri as a Nootropic This double-blind placebo-controlled investigation was done at Swinburne University in Australia. 107 healthy participants were given 300 mg of Bacopa Monnieri extract for 90 days. After 90 days, the people who took B. Monnieri extract showed significant improvement in spatial memory, memory accuracy and their ability to process visual information.83 Bacopa Monnieri for Stress Reduction Bacopa is likely best known for reducing stress. Recent research at Swinburne University of Technology in Australia confirmed this in the lab. In this double-blind, placebo-controlled cross-over study 17 healthy volunteers were given 320 mg or 640 mg of Bacopa extract. The study reported significant mood improvement, and decreased levels of cortisol. This study demonstrated Bacopa’s adaptogenic qualities. Bacopa Monnieri counteracted the effects of stress by regulating hormones involved in the stress response.84 Bacopa Monnieri for Longevity Long-term exposure to aluminum can increase your risk of Alzheimer’s Disease by 60 percent.85 (So check your underarm deodorant label before you read the rest of this section)! Research shows that Bacopa Monnieri can protect you from toxins that are harmful to your brain. Including aluminum. It prevents the buildup of toxins between and inside neurons. And prevents damage to the hippocampus. The area of your brain critical for learning, memory and cognitive power. Scientists at Jawaharlal Nehru University in India laced rats’ drinking water with aluminum chloride. The same aluminum that’s toxic to your brain. Some of the rats in this study had the protective power of Bacopa Monnieri going for them. Bacopa Monnieri protected the rat’s brains from oxidative damage from the aluminum. And it worked

as well as the Alzheimer’s drug selegiline. Bacopa restored the enzyme superoxide dismutase (SOD) to levels near normal. Indicating Bacopa Monnieri’s anti-aging potential.86 Dosage Notes There is no ‘right’ dosage of Bacopa. Each person’s body is unique. In general, use the lowest dosage that works for you. And Bacopa works better if taken a few days in a row rather than just once. Recommended dosage of Bacopa Monnieri containing 45% bacosides is 200 – 450 mg per day. Recommended dosage of Bacopa Monnieri containing 20% bacosides is 750 mg per day. Higher dosing should be divided equally with your first dose in the morning, and next dose early afternoon. Bacopa is fat-soluble so should be taken with a healthy fat source like organic, cold-pressed virgin olive or coconut oil. Fat helps your body absorb the compounds in Bacopa that bring you benefit. And helps deliver it into your brain cells. Side Effects Side effects for Bacopa are rare when taken as directed. But can include fatigue and upset stomach. Available Forms The bioactive component of Bacopa Monnieri is Bacoside A. Which is a mixture of saponins with bacoside A3, bacopaside II, and jujubogenin isomer of bacopasaponin C. Bacopa supplements are available as a powder, capsules and tablets. Check the label for the concentration of Bacosides. A Bacopa extract with a higher Bacoside concentration requires a lower dose. Nootropics Expert® Recommendation Bacopa Monnieri up to 450 mg per day I recommend using Bacopa Monnieri as a nootropic supplement. Your body does not make Bacopa Monnieri on its own. So you must take it as a supplement. B. Monnieri is especially helpful for those suffering from anxiety and stress. Studies show it helps stop and reverse the devastating effects of stress on your brain, and body. This nootropic helps repair damage to neurons and synapses caused by chronic stress. Bacopa is a powerful adaptogen. Which means it helps increase the effect of certain hormones when activity is low. And will block excess stimulation when activity is high. Bacopa Monnieri is also helpful for those suffering from anxiety and panic disorders. A study published in Phytomedicine showed the calming effect of this herb was equal to the drug Ativan (lorazepam). Without the side effects.

The ancient Ayurvedic texts knew what we’re only now discovering. That Bacopa is a powerful memory enhancer. Recent studies in Australia and the USA show B. Monnieri helps improve word recall, memory scores, attention and learning. You can safely take up to 450 mg of Bacopa Monnieri extract (45% Bacosides) daily if needed. Half the dose first thing in the morning. And the other half early afternoon.

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Cat’s Claw Cat’s Claw has been shown to increase Brain-Derived Neurotrophic Factor, fight inflammation and free radical damage, repair DNA, alleviate depression, and improve cognition and focus Cat’s Claw (Uncaria tomentosa, Uña de Gato, or Savéntaro) is a South American vine used as a nootropic with potent anti-inflammatory and antioxidant effects that support DNA repair, immune function and normal cell division.87 Cat’s Claw is a large, woody vine that gets its name from the hook-like thorns on the leaf stem resembling the claws of a cat. Cat’s Claw is indigenous to the Amazon rainforest and other tropical areas of South and Central America. Cat’s Claw has been used medicinally by the Aguaruna, Asháninka, Cashibo, Conibo, and Shipibo tribes of Peru for at least 2,000 years. The Asháninka use Cat’s Claw for everything from asthma to urinary tract infections to cancer. I won’t go into the long list of ailments Cat’s Claw is used for here because we’re focusing on the cognitive benefits of this herb. Just rest assured, Cat’s Claw has an amazing track record. Most of the commercially grown Cat’s Claw (Uncaria tomentosa) we get for nootropic use is from Peru. Cat’s Claw is rich in phytochemicals, alkaloids, glycosides, tannins, flavonoids, sterol fractions and other compounds. Ignore the marketing hype of “good alkaloids”, “bad alkaloids” and “TAO-Free” for Cat’s Claw. Independent research since the early 1970’s in animals and humans have used everything from freezedried ground root and bark to individual extracts of specific Cat’s Claw compounds. Cat’s Claw has been shown to decrease inflammation of arthritis88, prevent DNA damage89, reduce free radical damage90, reduce cancer91, controls pain through serotonin (5-HT2) receptors92, and much more. How does Cat’s Claw work in the Brain? Cat’s Claw boosts brain health and function in several ways. But two in particular stand out. 1. Cat’s Claw is a neuroprotectant. Cat’s Claw and its extracts have long been used to treat arthritis, asthma, chronic inflammation, immune disorders, pain, wound healing, and tumors. Some of the more recent research has focused on the cognitive benefits of Cat’s Claw. And using Cat’s Claw to protect brain function and cognition. One study demonstrated that an extract of Cat’s Claw could enhance DNA repair in the brain.93 Another study showed Cat’s Claw extract boosting Tryptophan levels which could have a profound effect on serotonin and mood.94 Dozens of other studies show Cat’s Claw possessing antioxidant properties, antiinflammatory, an immune modulator, anti-tumor, antihypertensive, as well as prevention of stroke.95 2. Cat’s Claw can increase memory and learning. Cat’s Claw extracts can help learning and

memory in a healthy as well as a damaged brain. Research shows certain alkaloid extracts of Cat’s Claw can help repair brain cells damaged by stroke or dysfunction of the acetylcholine receptors. The Cat’s Claw alkaloid Rhynchophylline is a NMDA antagonist. 96 Selectively restricting NMDA receptors helps tone down hyperactivity and overstimulation. Providing a calm mind for clear cognition and learning. How things go bad Chronic stress, anxiety and free radicals (oxidation) damage your brain. This damage can manifest in several ways including memory loss, brain fog, anxiety, depression, and even neurodegenerative diseases like Alzheimer’s and Parkinson’s. ↓ Chronic stress reduces memory ↓ Free radicals kill brain cells ↓ Neuroplasticity declines degrading long-term potentiation97 ↓ Brain -Derived Neurotrophic Factor Declines ↑ NMDA receptors are over-active Under conditions of chronic stress or depression caused by everyday living or chronic pain, your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition and decisionmaking all suffer as a result. Cat’s Claw benefits Research from hundreds of studies have shown that Cat’s Claw and its extracts: • • • • • • • • • • • •

Potent antioxidant and anti-inflammatory Relieves pain through influence on serotonin receptors Enhances DNA repair Boosts immune health Suppresses tumor proliferation Protects against damage from stroke98 Improves memory and cognition Restores the availability of acetylcholine Improves cerebral circulation Reduces stress Helps repair brain cells Eliminates free radicals from within brain cells

How does Cat’s Claw feel? Cat’s Claw is a potent anti-inflammatory and immune booster. Most neurohackers report a dramatic decrease in arthritis and joint pain.

Cat’s Claw has a reputation for reducing the symptoms of Lyme Disease and Crohn’s Disease. Most who use Cat’s Claw regularly report they don’t get sick as often, experience less pain, and have an easier time getting to sleep and sleeping through the night. Some neurohackers use Cat’s Claw to relieve an over-active mind. Cat’s Claw can calm racing thoughts and make it easier to focus. The Research Cat’s Claw Improves Memory Cat’s Claw has been reported to restore memory both in the lab and in user reviews. One method of increasing memory with Cat’s Claw may be through promoting long-term potentiation. Rhynchophylline (Rhy) is an alkaloid isolated from Cat’s Claw that has long been recommended for treatment of diseases in the central nervous system. Researchers in China investigated using Rhy in stroke victims. Rats were injected with Rhynchophylline once daily for 4 consecutive days before surgery, and then one more injection after surgery. The surgery created a stroke in the rats by severing a middle artery in their brain. The team found that Rhynchophylline prevented brain damage from the stroke while increasing BDNF expression.99 Cat’s Claw extract also activated the PI3K/Akt/mTOR signaling pathway which is a necessary component of long-term potentiation.100 Long-term potentiation is the strengthening of synapses between neurons which is one of the major mechanisms in the brain behind learning and memory. Cat’s Claw Suppresses Cancer Cat’s Claw has traditionally been used by indigenous cultures in South America and other parts of the world to treat cancer. And several studies caught my attention because I came across two Cat’s Claw customer reviews on how the herb helped them survive a dismal diagnosis of brain cancer. Austrian researchers used Cat’s Claw extracts (isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5)) on human leukemia T cells on the lab. Four of the five extracts not only stopped cancer cell growth but killed the cancer cells outright.101 Another USA research team found that Cat’s Claw has the ability to regulate immune system cytokines that help your body’s defense against cancer.102 An Italian study investigated using Cat’s Claw extract on breast cancer. The researchers found that Cat’s Claw prevented the growth of 90% of breast cancer cells in the lab.103 A research team in Mexico found that Cat’s Claw extract stopped Wnt-signaling activity in cancer cells.104 The Wnt-signaling pathway is implicated in glioblastoma, the most common and most

aggressive cancer that occurs in the brain. Cat’s Claw Repairs DNA and Boosts Immune System Researchers in Sweden used the C-MED-100 (AC11®) extract of Cat’s Claw in rats and men. Rats were given doses of 0, 5, 10, 20, 40 and 80 mg of the Cat’s Claw extract per kg of body weight for 8 consecutive weeks. White blood cell counts in the 40 and 80 mg treatment groups were significantly elevated over controls. In male volunteers, healthy men were given 5 mg of Cat’s Claw extract per kg of body weight for 6 consecutive weeks. Again white blood cell count was significantly elevated in the male volunteers. The researchers also found that DNA repair got a significant boost by Cat’s Claw extract after whole body irradiation in the rats.105 A 2nd study by the same research group used C-MED-100 extract with 12 healthy men. The volunteers received either 250 mg of the extract, 350 mg of extract or a placebo daily for 8 weeks. Hydrogen peroxide was used to induce DNA damage in the men. Both extracts provided a significant increase in DNA repair compared to the controls who received a placebo.106 Dosage Notes Cat’s Claw is well tolerated by most and considered non-toxic. Cat’s Claw is available in tablets, capsules or as a water or alcohol extract tincture. Ground or freezedried Cat’s Claw bark can also be taken as a tea. Cat’s Claw recommended dosage is one 100 mg capsule per day for arthritis. And one 250 or 350 mg capsule per day for cognitive and immune support. Standardized Cat’s Claw vine or root bark extracts usually contain 3% alkaloids and 15% phenols. Don’t mistake Uncaria tomentosa for Uncaria guianensis which is another type of Cat’s Claw from the Amazon basin. U. guianensis has a much lower alkaloid content. Side Effects Side effects are rare with Cat’s Claw. But may include diarrhea, dizziness or nausea. Those with autoimmune diseases, skin grafts, tuberculosis or receiving organ transplants should not use Cat’s Claw because of its effects on the immune system. Cat’s Claw can stimulate the immune system and will counteract any medication you’re using to suppress your immune system. Cat’s Claw is known for lowering blood pressure. So if you have an issue with low blood pressure, or on high blood pressure medication you should not use Cat’s Claw. Cat’s Claw may increase the risk of bleeding so don’t take this herb if you have a bleeding disorder, are

on blood thinners, or are planning surgery. Available Forms Cat’s Claw powdered inner bark of the vine is usually the least expensive form and comes in 1,000 mg capsules. Cat’s Claw standardized extract usually contains 1.5% to 3% oxindole alkaloids and 15% phenols. AC-11® (C-MED-100®) is a patented hot-water extract of Cat’s Claw. It’s standardized to 8% Carboxyl Alkyl Esters. Saventaro® POA Cat’s Claw is a standardized and patented form of Cat’s Claw with 1.3% pentacyclic oxindole alkaloids (POA) (260 mcg) and is purified to be free of tetracyclic oxindole alkaloids (TOA). Nootropics Expert® Recommendation Cat’s Claw standardized extract up to 250 – 350 mg per day I recommend using Cat’s Claw as a nootropic supplement. Your body does not make Cat’s Claw. So you must take it as a supplement to get its effects. This ancient herb has a long history of safe use as an herbal remedy in many parts of the world. Cat’s Claw (Uncaria tomentosa) is native to South America and the form referred to throughout this section. Cat’s Claw is mostly used as an anti-inflammatory and immune system booster. Cat’s Claw is especially helpful to those dealing with the symptoms of Lyme or Crohn’s Disease. And for those dealing with arthritis, joint pain or Carpel Tunnel Syndrome. AC-11® is often used in nootropic circles for cognitive support. Dosage of AC-11® is 350 mg per day. Cat’s Claw can improve your mood and memory. And protect your brain from free radicals and the toxins you’re exposed to everyday. Cat’s Claw as a nootropic has the potential to keep you mentally sharp for life. You can even out the stress and anxiety of your day by sipping Cat’s Claw tea. Or use a supplement as a cognitive enhancer.

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Choline Bitartrate Choline Bitartrate is known to increase cognition and brain function, improve focus and motivation, and reduce fatigue Choline Bitartrate is choline combined with tartaric acid. Binding choline to tartaric acid increases bioavailability. Choline (2-hydroxy-N,N,N-trimethyl-ethanaminium) is a primary building block for the critical neurotransmitter acetylcholine (ACh). Choline was declared an essential nutrient by the Food and Nutrition Board of the National Institute of Medicine (USA) in 1998. Choline is considered an essential nutrient because when your body uses it faster than it can produce it, you need supplemental choline either from food or a supplement. Choline is found in foods such as fish, beef steak, liver, chicken liver, eggs, cod, broccoli, peanut butter, and milk. You need choline for the production of the neurotransmitter acetylcholine. And to form phosphatidylcholine (PC), used in building cell membranes. Your brain uses acetylcholine to maintain clear communication. In fact, it’s used to maintain communication between all the cells in your body. In fact, choline is so vital to cognition and nerve function that, without it, we couldn’t move, think, sleep or remember anything. When choline is in short supply, your brain goes on a scavenger hunt. And starts to steal choline from nerve cell membranes. In your brain’s attempt to maintain normal acetylcholine signaling, it starts taking cells apart.107 This works in the short term. Your brain uses this technique to keep your memory and other functions running smoothly. But in the long run it takes a toll on your brain at the cellular level.108 This is the primary reason you need to add a choline supplement to your nootropic stack. Choline Bitartrate vs. CDP-Choline vs. Alpha GPC: What’s the Difference? Choline is a water-soluble nutrient, and its composition is similar to B-vitamins. Choline Bitartrate, CDP-Choline, Choline Citrate and Alpha GPC are all sources of choline. Choline Bitartrate: An economical form of choline, and about 40% choline by weight. So 1 gram of Choline Bitartrate offers 400 mg of actual choline. It does not cross the blood-brain barrier as readily as other sources of choline. So you won’t experience the same level of nootropic benefits as with Alpha GPC or CDP-Choline. CDP-Choline (cytidine 5′-diphosphocholine): Is only about 18% choline by weight. Your body

naturally synthesizes choline into CDP-Choline (Citicoline). It’s then converted to phosphatidylcholine (PC) which is one of two fatty acids that make up the outer layer of cell membranes. And PC provides the choline needed to synthesize acetylcholine (ACh). Alpha GPC: About 40% choline by weight and easily crosses the blood-brain barrier. Alpha GPC naturally occurs in your brain as a byproduct of phosphatidylcholine (PC). When your brain needs more choline, and the choline floating around in your brain is running low, it breaks down PC from cell membranes. And turns it into Alpha GPC. Your body and brain loves it when you use choline. Because it doesn’t have to cannibalize its own cells to get more choline. How does Choline Bitartrate Work in the Brain? Choline Bitartrate boosts brain health and function in several ways. But two in particular stand out. 1. Choline Bitartrate boosts acetylcholine, a neurotransmitter tied to memory and overall brain function. Choline Bitartrate is a precursor to acetylcholine. Improving the efficiency of communications between neurons in your brain. This increase in neural signaling boosts memory, learning, cognitive processing and mental clarity. A research team in the Netherlands set out to determine if choline bitartrate could affect coordination of movement and visual perception. In this study, they worked with a group of 28 people who took 2 grams of choline bitartrate or a placebo. An hour and 10 minutes after they took the choline or placebo, they had participants try to hit the center of a target. Participants who took the choline were not only far more accurate at hitting the target center than the placebo group. They also did it faster. The researchers concluded there was a “choline-induced bias” towards precision, speed and accuracy. They even measured pupil-size in participants. And determined, “The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system.”109 2. Choline Bitartrate Boosts Memory. Researchers and medical professionals have long known about poor memory in people with a choline deficiency. A study at Northwestern University in Chicago tested people with a choline deficiency. They gave them a series of memory tests and found their scores below average. In this study, they then gave one group extra choline, and the others were given a placebo. After 24 weeks, both groups repeated the memory tests. The group who received extra choline showed a dramatic improvement in memory. The placebo group performed poorly as expected with scores the same as on the original test.110

How things go bad As we get older, our brain chemistry and energy metabolism changes. This can happen at any age once we enter our adult years. ↓ Brain fog and/or a sense of confusion ↓ Fatigue or lack of energy ↓ Unable to learn new things ↓ Memory loss and poor recall ↓ Feeling distracted or irritable ↓ Poor balance And these changes can happen at any age. Our bodies are influenced by the food we eat (and what we don’t eat!), what we drink, lifestyle habits, and even the air we breathe. Choline Bitartrate can help reverse cognitive decline. It can help you perform better in your work, and at school. By boosting acetylcholine and repairing neural cell membranes. Choline Bitartrate benefits Research from hundreds of studies have shown that choline will: • • • • • • •

Eliminate brain fog and confusion Boost energy Improve learning Enhance memory and recall Help focus and reduce irritability Improve physical performance Eliminate fatigue

Choline Bitartrate is water-soluble. After it’s digested it will enter your bloodstream and cross the blood-brain barrier. Once in your brain it boosts neural signal transmission and helps repair neurons. Choline Bitartrate improves your brain function and memory by increasing the production of acetylcholine. And prevents neurons from getting cannibalized when your brain is searching for more choline. How does Choline Bitartrate feel? After taking Choline Bitartrate you should feel a boost in your ability to think, mood should improve, and your energy level should go up. Choline Bitartrate influences the level of acetylcholine in your brain. This crucial neurotransmitter affects memory, cognition, recall and learning.

Low levels of choline will leave you with brain fog and an inability to think clearly. You may also experience a drop in mood and some irritability. If you’re using anything from the racetam-family of nootropics and you experience a headache – your brain is likely starved for choline. The Research Choline Boosts Cognition The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents in the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adults. And is now on its 3rd generation of participants. This study of Framingham Offspring involved 1,391 dementia-free subjects. Ages ranged from 36 – 83 years. The participants underwent a food-frequency questionnaire, and MRI brain scan. The study was in two parts, from 1991 to 1995, and 1998 to 2001. Study participants were tested for verbal memory, visual memory, verbal learning and executive function. And a MRI-scan measured brain volume. The study concluded that those residents with a higher choline intake was directly related to significantly better cognitive performance.111 Choline Bitartrate Helps with Exercise and Muscle Performance Choline Bitartrate boosts mental energy, focus and concentration. All critical for physical activity and athletic performance. Choline’s effect on your metabolism and neurotransmitters in the brain produce quicker reaction times. And shorten the time needed for mental processing. Choline helps improve your energy levels, mood, and recovery time following a workout. It is also critical for muscle nerve function, and in preventing fatigue, muscle aches and pain following a workout. When your muscles move, choline is needed to activate the neurotransmitter acetylcholine (ACh). ACh sends signals to muscles, and makes them move.112 Dosage Notes Recommended Choline Bitartrate dosage is 500 mg to 3,000 mg per day. You can use higher doses of Choline Bitartrate because this is a water-soluble version of choline. And a limited amount of this choline source will cross the blood-brain barrier. Other fat-soluble versions of choline such as Alpha GPC and CDP-Choline will more readily cross the blood-brain barrier and make its way into your cells. So lower doses are required. Side Effects

Recommended dosages even for extended periods are considered well-tolerated and safe. While Choline Bitartrate is considered non-toxic, it is possible to experience toxicity with too much choline in your body. If you experience trouble sleeping, headache, diarrhea, low or high blood pressure, nausea, blurred vision or chest pain – you should stop using Choline Bitartrate. Available Forms Choline Bitartrate is sold in capsule or powder form. Capsules are usually 500 mg each. Many of the nootropic stacks available on the market, and even some brand name vitamins contain Choline Bitartrate in their formula. Nootropics Expert® Recommendation Choline Bitartrate 500 – 3,000 mg per day I recommend using Choline Bitartrate as a nootropic supplement. Your body does not make Choline Bitartrate on its own. But some versions of choline naturally occur in your body and brain. Choline sources like Alpha GPC and CDP-Choline. You do get some choline from the food you eat. But studies show we don’t get an adequate supply of choline from food sources in our modern diet. Choline Bitartrate is especially helpful for those suffering from age-related cognitive decline. Studies show supplemental choline helps stop or reverse brain degeneration like Alzheimer’s Disease, and other cognitive disorders. Especially in the early to mid-stages of the disease. We suggest starting with a dose of 500 to 1,000 mg daily. Choline Bitartrate is a good compliment to a stack including any nootropics from the racetam-family. Piracetam for example affects your neuroreceptors for acetylcholine. So stacking Piracetam and Choline Bitartrate boosts acetylcholine activity even more. If you’re on a tight budget and you need choline, Choline Bitartrate is a great place to start. It is the most affordable version of Choline available. Particularly when purchased in bulk powder form. You just need more of it than other choline sources like Alpha GPC or CDP-Choline. Use Choline Bitartrate at a ratio of 6:1. For example, 1,000 mg of Choline Bitartrate with 6,000 mg of Piracetam. If you get a racetam-headache add more choline to your stack.

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Choline Citrate Choline Citrate is known to increase cognition and brain function, improve focus and motivation, and reduce fatigue Choline Citrate is choline combined with citrate which is an ester of citric acid. Binding choline to citrate contributes to the synthesis of acetylcholine (ACh) in your brain. The two precursors required for acetylcholine (ACh) synthesis are Choline (2-hydroxy-N,N,N-trimethylethanaminium) and the enzyme acetyl-Coenzyme A (Acetyl-CoA). Citrate is a citric acid ester which provides a third of the acetyl groups used in the acetylcholine (ACh) synthesis process.113 You can get citric acid from citrus fruit like lemons and limes. And citrate plays another important role in the brain. Citrate is an intermediate in the Krebs cycle (also known as the TCA cycle or Tricarboxylic Acid cycle, or Citric acid cycle). Citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate for aconitase and is converted in aconitic acid. This cycle ends with the regeneration of oxaloacetate. This series of chemical reactions is the source of 2/3’s of the energy we get from food. Most of the energy made available by these steps is transferred to form NADH. Which then drives adenosine triphosphate (ATP) synthesis within mitochondria and provides the energy needed for brain cells.114 Now let’s go back to acetylcholine for a minute. Your brain uses acetylcholine to maintain clear communication. In fact, it’s used to maintain communication between all the cells in your body. And you need choline for cognition, memory, sleep and even maintaining your balance, stability and mobility. Your brain needs choline to function. When choline is in short supply, your brain goes on a scavenger hunt. And starts to steal choline from nerve cell membranes. In your brain’s attempt to maintain normal acetylcholine signaling, it starts taking cells apart.115 This works in the short term. Your brain uses this technique to keep your memory and other functions running smoothly. But in the long run it takes a toll on your brain at the cellular level.116 And that’s why you should consider adding choline citrate to your nootropic stack. Choline Citrate vs. Choline Bitartrate vs. CDP-Choline vs. Alpha GPC: What’s the Difference? Choline is a water-soluble nutrient and its composition is similar to B-vitamins. Choline Citrate, CDPCholine, Choline Bitartrate and Alpha GPC are all sources of choline. Choline Citrate: An economical form of choline combined with citrate, and about 50% choline by weight. So 1 gram of Choline Citrate offers 500 mg of actual choline. Choline Citrate not only provides

your brain with choline, but comes with one of the acetyl groups necessary for acetylcholine (ACh) synthesis. Choline Bitartrate: An economical form of choline, and about 40% choline by weight. So 1 gram of Choline Bitartrate offers 400 mg of actual choline. It does not cross the blood-brain barrier as readily as other sources of choline. So you won’t experience the same level of nootropic benefits as with Alpha GPC or CDP-Choline. CDP-Choline (cytidine 5′-diphosphocholine): Is only about 18% choline by weight. Your body naturally synthesizes choline into CDP-Choline (Citicoline). It’s then converted to phosphatidylcholine (PC) which is one of two fatty acids that make up the outer layer of cell membranes. And PC provides the choline needed to synthesize acetylcholine (ACh). Alpha GPC: About 40% choline by weight and easily crosses the blood-brain barrier. Alpha GPC naturally occurs in your brain as a byproduct of phosphatidylcholine (PC). When your brain needs more choline, and the choline floating around in your brain is running low, it breaks down PC from cell membranes. And turns it into Alpha GPC. Your body and brain loves it when you use choline. Because it doesn’t have to cannibalize its own cells to get more choline. How does Choline Citrate work in the Brain? Choline Citrate boosts brain health and function in several ways. But two in particular stand out. 1. Choline Citrate boosts acetylcholine (ACh). Acetylcholine is a neurotransmitter tied to memory and overall brain function. Choline Citrate is a precursor to acetylcholine. Improving the efficiency of communications between neurons in your brain. This increase in neural signaling boosts memory, learning, cognitive processing and mental clarity. But researchers found that circulating choline in the brain decreases with age. This study recruited younger adults between 20 and 40 years, and older adults between 60 and 85 years. After fasting overnight, the subjects received 50 mg of a choline supplement per kilogram of body weight. Labs were drawn to determine choline concentration in the blood. And proton magnetic resonance spectroscopy (1H-MRS) was performed to determine the relative concentration of cytosolic choline-containing compounds in the brain. Both tests were done before, and 3 hours after choline supplementation. Levels of choline in the blood and brain of study subjects were similar before choline supplementation. But after choline supplementation, the younger subjects showed a 60% increase of choline in their blood and brain. The older subjects showed only a 16% increase in choline levels. The researchers concluded circulating choline in the brain decreases with age. And given the key role of

choline in brain function, this change may be a contributing factor in onset of late life neurodegeneration and dementia.117 So according to this study, older adults should be supplementing with higher doses of a choline supplement like Choline Citrate to maintain cognitive function compared to younger adults. 2. Choline Citrate Boosts Memory. Researchers and medical professionals have long known about poor memory in people with a choline deficiency. A study at Northwestern University in Chicago tested people with a choline deficiency. They gave them a series of memory tests and found their scores below average. In this study, they then gave one group extra choline, and the others were given a placebo. After 24 weeks, both groups repeated the memory tests. The group who received extra choline showed a dramatic improvement in memory. The placebo group performed poorly as expected with scores the same as on the original test.118 How things go bad As we get older, our brain chemistry and energy metabolism changes. But choline deficiency can happen at any age from infancy through to our late adult years. ↓ Brain fog and/or a sense of confusion ↓ Fatigue or lack of energy ↓ Unable to learn new things ↓ Memory loss and poor recall ↓ Feeling distracted or irritable ↓ Poor balance Our bodies are influenced by the food we eat (and what we don’t eat!), what we drink, lifestyle habits, and even the air we breathe. Choline Citrate can help reverse cognitive decline. It can help you perform better in your work, and at school. By boosting acetylcholine and repairing neural cell membranes. Choline Citrate benefits Research from hundreds of studies have shown that choline will: • • • • •

Eliminate brain fog and confusion Boost energy Improve learning Enhance memory and recall Help focus and reduce irritability

• •

Improve physical performance Eliminate fatigue

Choline Citrate is water-soluble. After it’s digested it will enter your bloodstream and cross the bloodbrain barrier. Once in your brain it boosts neural signal transmission and helps repair neurons. Choline Citrate improves your brain function and memory by increasing the production of acetylcholine. And prevents neurons from getting cannibalized when your brain is searching for more choline. And the citric acid part of Choline Citrate is a critical part of the KREBS cycle in your brain cells. Leading to support of brain cell energy production within mitochondria. Providing you with mental energy and eliminating fatigue. How does Choline Citrate feel? After taking Choline Citrate you should feel a boost in your ability to think, mood should improve, and your energy level should go up. Choline Citrate influences the level of acetylcholine in your brain. This crucial neurotransmitter affects memory, cognition, recall and learning. Low levels of choline will leave you with brain fog and an inability to think clearly. You may also experience a drop in mood and some irritability. If you’re using anything from the racetam-family of nootropics and you experience a headache – your brain is likely starved for choline. The Research Choline Boosts Cognition The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents in the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adults. And is now on its 3rd generation of participants. This study of Framingham Offspring involved 1,391 dementia-free subjects. Ages ranged from 36 – 83 years. The participants underwent a food-frequency questionnaire, and MRI brain scan. The study was in two parts, from 1991 to 1995, and 1998 to 2001. Study participants were tested for verbal memory, visual memory, verbal learning and executive function. And a MRI-scan measured brain volume. The study concluded that those residents with higher choline intake demonstrated significantly better cognitive performance.119 Choline Citrate Helps with Exercise and Muscle Performance Choline Citrate boosts mental energy, focus and concentration. All critical for physical activity and

athletic performance. Choline’s effect on your metabolism and neurotransmitters in the brain produce quicker reaction times. And shorten the time needed for mental processing. Choline helps improve your energy levels, mood, and recovery time following a workout. It is also critical for muscle nerve function, and in preventing fatigue, muscle aches and pain following a workout. When your muscles move, choline is needed to activate the neurotransmitter acetylcholine (ACh). ACh sends signals to muscles, and makes them move.120 Researchers found that providing 2 grams of choline prior to exercise prevented a fall in choline levels. And raised choline levels above baseline values for up to 2 hours after exercise. The researchers found that choline citrate and choline bitartrate were equally effective. One randomized, placebo-controlled study found improvements in running times by a significant amount over a 20-mile course when compared to those using a placebo.121 Dosage Notes Recommended Choline Citrate dosage is 500 mg to 3,000 mg per day. You can use higher doses of Choline Citrate because this is a water-soluble version of choline. And a limited amount of this choline source will cross the blood-brain barrier. Studies have found that age has a significant effect on choline uptake into the brain. So older neurohackers are encouraged to use larger doses of Choline Citrate compared to younger neurohackers. Note that other fat-soluble versions of choline such as Alpha GPC and CDP-Choline will more readily cross the blood-brain barrier and make its way into your cells. So lower doses are required. Side Effects Recommended dosages even for extended periods are considered well-tolerated and safe. While Choline Citrate is considered non-toxic, it is possible to experience toxicity with too much choline in your body. If you experience trouble sleeping, headache, diarrhea, low or high blood pressure, nausea, blurred vision or chest pain – you should stop using Choline Citrate. Or reduce your dose. Available Forms Choline Citrate is sold in capsule or powder form. Capsules are usually 500 – 650 mg each. Some ready-made nootropic stacks, and even some brand name vitamins contain Choline Citrate in their formula. Nootropics Expert® Recommendation Choline Citrate 500 – 3,000 mg per day

I recommend using Choline Citrate as a nootropic supplement. Your body does not make Choline Citrate on its own. But some versions of choline naturally occur in your body and brain. Choline sources like Alpha GPC and CDP-Choline. You do get some choline from the food you eat. But studies show we don’t get an adequate supply of choline from food sources in our modern diet. And as we age, our bodies have a difficult time using the choline we get from food. Choline Citrate is especially helpful for those suffering from age-related cognitive decline. Studies show supplemental choline helps stop or reverse brain degeneration like Alzheimer’s Disease, and other cognitive disorders. Especially in the early to mid-stages of the disease. I suggest starting with a dose of 500 to 1,000 mg daily. Choline Citrate is a good compliment to a stack with any nootropics from the racetam-family. Piracetam for example affects your neuroreceptors for acetylcholine. So stacking Piracetam and Choline Citrate boosts acetylcholine activity even more. If you’re on a tight budget and you need choline, Choline Citrate is a great place to start. It is one of the most affordable versions of Choline available. Particularly when purchased in bulk powder form. You just need more of it than other choline sources like Alpha GPC or CDP-Choline. Use Choline Citrate at a ratio of 1:6. For example, 1,000 mg of Choline Citrate with 6,000 mg of Piracetam. If you get a racetam-headache add more choline to your stack.

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CDP-Choline (Citicoline) CDP-Choline is known to increase cognition and brain function, improve focus and motivation, and reduce fatigue CDP-Choline (Cytidine Diphosphate Choline or cytidine 5’-diphosphocholine) is also known as Citicoline. This naturally occurring choline source is present in every cell in your body. CDP-Choline is unique as a choline source. Once it’s digested it separates into cytidine and choline. When it gets to your brain it converts back to CDP-Choline. Choline is considered an essential nutrient because your body uses it faster than it can produce it. So you need to supplement choline either from food or a supplement. You need choline for the production of the neurotransmitter acetylcholine. And to form phosphatidylcholine (PC), used in building cell membranes. In fact, choline is so vital to cognition and nerve function that, without it, we couldn’t move, think, sleep or remember anything. This choline is needed to synthesize the neurotransmitter acetylcholine (ACh). ACh is a primary neurotransmitter released by neurons. This electrical signaling between neurons is involved in memory, learning, cognition and recall. Cytidine is a component of Ribonucleic acid (RNA). This molecule is involved in coding, decoding, regulation and the expression of genes. But once it gets into the brain, it converts to uridine. The signaling going on between neurons tends to grab choline molecules from cell membranes when choline is in short supply. This is where uridine steps in. It repairs those same cell membranes. To maintain neuron integrity. CDP-Choline vs. Alpha GPC vs. Choline Bitartrate: What’s the Difference? Choline is a water-soluble nutrient similar in composition to B-vitamins. CDP-Choline, Alpha GPC, Choline Citrate and Choline Bitartrate are all sources of choline. CDP-Choline (cytidine 5′-diphosphocholine): Is about 18% choline by weight and easily crosses the blood-brain barrier. Your body naturally synthesizes choline into CDP-Choline (Citicoline) in your brain. Taken as a supplement, it’s then converted to cytidine and choline in your gut. Once it crosses the blood-brain barrier it’s converted back to CDP-Choline. The choline then assists cell membranes and helps create acetylcholine. The added benefit of CDP-Choline is with cytidine. Cytidine can convert into uridine which is critical in the brain. Uridine is needed to synthesize the phosphatidylcholine (PC) in neuron membranes. It helps repair neurons.

Choline Bitartrate: An economical form of choline, and about 40% choline by weight. So 1 gram of Choline Bitartrate offers 400 mg of actual choline. It does not easily cross the blood-brain barrier. So you won’t experience the same level of nootropic benefits as with Alpha GPC or CDP-Choline. Alpha GPC: About 40% choline by weight and easily crosses the blood-brain barrier. Alpha GPC naturally occurs in your brain as a byproduct of phosphatidylcholine (PC). When your brain needs more choline, and the choline floating around in your brain is running low, it breaks down PC from cell membranes. And turns it into Alpha GPC. Your body and brain loves it when you use Alpha GPC. Because it doesn’t have to cannibalize its own cells to get more choline. How does CDP-Choline Work in the Brain? CDP-Choline boosts brain health and function in several ways. But two in particular stand out. 1. CDP-Choline is metabolized in the gut wall and liver to form choline and cytidine. Once choline and cytidine cross the blood-barrier they re-synthesize back into CDP-Choline (Citicoline).122 In the brain choline aids in the synthesis of acetylcholine. And the release of dopamine.123 Acetylcholine is a neurotransmitter associated with memory and learning. 2. CDP-Choline helps repair neural membranes. Choline is a precursor to the neurotransmitter acetylcholine (ACh) in your brain. ACh carries nerve impulses across synapses. And then is broken down by enzymes. ACh is then reassembled for reuse. But this breakdown/reassembly process isn’t foolproof. Some ACh gets lost in the process. So your brain goes looking for more choline to make ACh. If there isn’t enough choline in your blood, it gets it from the phosphatidylcholine (PC) that makes up the outside of the cell membrane of your neurons. The PC in the cell membrane releases choline to help make acetylcholine. When your neurons lose too much choline, they lose integrity. Nerve impulses break down, and cognitive abilities decline.124 Scientists in the lab at MIT showed that this is where uridine steps in. The cytidine in CDP-Choline converts to uridine in your body. And it works as a bridge between choline and neuron membrane synthesis. Uridine is needed to synthesize the PC in neuron membranes. It is first converted to CDP-Choline. Which is then synthesized into new PC. This new PC can then repair damaged neuron membranes. Membranes that were raided to make acetylcholine.125 How things go bad As we get older, our brain chemistry and energy metabolism changes. This can happen at any age once we enter our adult years.

↓ Brain cell membranes degenerate ↓ Recall, reaction time and mood diminish ↓ Acetylcholine levels decline126 All of these changes can happen at any age. And our bodies are influenced by the food we eat, what we drink, lifestyle habits, the air we breathe and more. So CDP-Choline can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting acetylcholine and dopamine. And rebuilding neurons in the brain. CDP-Choline benefits Research from hundreds of studies have shown that CDP-Choline will: • • • • • • •

Boost cognition127 Increase brain energy and speed up formation of brain membranes128 Boost production of acetylcholine129 Increase blood flow to the brain130 Offset the harmful effects of stroke131 Improve memory and learning ability132 Boost cognitive performance and memory in Alzheimer’s patients133

CDP-Choline is water-soluble and quickly enters your brain after you take it. In fact, studies show it has nearly 100% bioavailability in your body. Take it orally or intravenously and your body absorbs the same amount. Once in your brain it boosts signal transmission, and repairs neurons. CDP-Choline improves your brain function and memory by directly increasing levels of acetylcholine and dopamine. And repairs neurons at the same time. How does CDP-Choline feel? The most profound indication of the power of this supplement is with those who have suffered a stroke. Stroke survivors report that after continued usage of CDP-Choline, most of the noticeable effects of the stroke are gone. Including muscle paralysis and weakness. Neurohackers report they are better able to concentrate and focus. And experience a significant boost in cognition. You can feel more mentally alert. And you may even ease the fatigue associated with clinical depression by using CDP-Choline. Some use CDP-Choline as an alternative to the stimulants prescribed for ADHD. The Research

In a study at the University of Utah, 75 healthy males were given 250 mg, 500 mg of CDP-Choline, or a placebo. Tests were recorded after 28 days of supplementation. The adolescent males receiving 250 or 500 mg of CDP-Choline showed improved attention and psychomotor speed. And reduced impulsivity compared to adolescent males who received placebo. This study indicates CDP-Choline is effective even in younger age groups. And can be particularly helpful to those dealing with ADHD.134 CDP-Choline Enhances Cognition A study published in Food and Nutrition Sciences assessed the potential cognitive-enhancing effects of Citicoline (CDP-Choline) in healthy, adult women. This double-blind, randomized, placebo-controlled trial worked with 60 healthy women from 40 – 60 years old. Each volunteer was given a daily dose of 250 mg or 500 mg of Citicoline, or a placebo for 28 days. The women who took either dose of Citicoline for 28 days showed a significant improvement in cognition. The researchers suggested that Citicoline may improve attentional performance in middle-aged women. And it might eliminate the attention deficits associated with central nervous system disorders (i.e. ADHD). CDP-Choline Improves Memory Researchers in Japan studied 16 men and women who were given either 500 mg or 2000 mg of Citicoline for 6 weeks. Magnetic resonance spectroscopy (MRS) was used to study the brains of the participants at the end of the study. The research team found ATP in the neurons of those in the study increased by over 14%. And membrane phospholipids were boosted by over 32%. These finding were in specific areas of the brain associated with cognition. And the effect was even more pronounced in the group that received the lower dose of Citicoline. The researchers concluded that Citicoline supplementation could help prevent cognitive decline associated with aging. Along with an increase in brain energy reserves and utilization. And an increase in the components needed to synthesize and maintain cell membranes. Dosage Notes Recommended CDP-Choline dosage is 250 - 500 mg per day. Taken no more than twice per day. Two daily doses would be one CDP-Choline dose in the morning, and one in the early afternoon. If you’re adding CPD-Choline to your stack with a racetam, a typical ratio would be 250 mg of Citicoline to 1 gram of Aniracetam or 4 grams of Piracetam. Side Effects

Recommended dosages even for extended periods are considered well-tolerated and safe. While CDPCholine is considered non-toxic, it is possible to experience toxicity with too much choline in your body. If you experience trouble sleeping, headache, diarrhea, low or high blood pressure, nausea, blurred vision or chest pain – you should stop using CDP-Choline. Available Forms CDP-Choline is sold in capsule and powder form. Capsules are usually 250 – 500 mg each. 500 mg of CDP-Choline in powder form is equivalent to 2-level 1/8 tsp scoops. Nootropics Expert® Recommendation CDP-Choline 250 - 500 mg per day I recommend using CDP-Choline as a nootropic supplement. CDP-Choline is brain food. And is a natural substance found in every cell in your body. You can get choline from some of the food you eat. But adequate levels of CDP-Choline are only found in organ meats like liver. So to get its benefits you must take it as a supplement. CDP-Choline is vital to maintaining optimal brain health. And has been shown to increase cognitive energy, boost brain function, enhance communication between neurons, and protect neural membranes from free radical damage. I suggest starting with a dose of 250 – 500 mg daily. And CDP-Choline is a great compliment to stack with any nootropic from the racetam-family. Anything that causes an increase in uptake of acetylcholine in your brain. You need to provide your brain with the CDP-Choline it is demanding. Or it starts cannibalizing your own brain cells to make more acetylcholine. Signs that you’re lacking adequate choline are headaches. Use CDP-Choline at a ratio of 1:4. For example, 250 mg of CDP-Choline to 1,000 mg of Aniracetam. Stroke survivors may want to up the dose to 2,000 mg per day.

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Centrophenoxine Centrophenoxine helps boost cognition & memory and has significant anti-aging benefits preventing and reversing neuronal decay Centrophenoxine (Lucidril® or meclofenoxate) is one of the original nootropics. Developed in France in 1959, Centrophenoxine is a combination of DMAE (dimethylethanolamine) and pCPA (parachlorphenoxyacetic acid). DMAE is an amine produced in small amounts in your brain. By preventing the use of choline by other tissues (including synthesis into acetylcholine), DMAE increases choline levels in the bloodstream. pCPA is a synthetic version of auxins (plant growth hormones). Auxins act like natural growth factor in plants. Once digested, Centrophenoxine breaks down into DMAE and pCPA in the liver. This combination was found to make DMAE more bioavailable in the body. And helps DMAE cross the blood-brain barrier more readily. Centrophenoxine can increase your brain energy levels by boosting oxygen flow. It helps flush out dangerous free radicals and cellular waste. And may help improve memory and cognition. Centrophenoxine vs. DMAE: What’s the Difference? DMAE is used to make Centrophenoxine. DMAE is found in small amounts in your brain. A good food source of DMAE is fish. But there is little evidence that DMAE as a supplement actually crosses the blood-brain barrier. And if it provides the brain enough choline needed to make acetylcholine. Centrophenoxine seems to solve the blood-brain barrier problem. Adding pCPA to DMAE helps DMAE enter your brain. And this combination also seems to be an effective way to boost acetylcholine for some neurohackers. If you’re considering adding DMAE to your stack, Centrophenoxine may be a better alternative. How does Centrophenoxine Work in the Brain? Centrophenoxine boosts brain health and function in several ways. But two in particular stand out. 1. Centrophenoxine helps improve memory.135 One study shows it does it by boosting acetylcholine (ACh) in your brain by increasing the enzyme acetylcholinesterase.136 Researchers set out to prove this in a clinical trial using lab rats. In this study they compared Centrophenoxine with DMAE. And determined that DMAE was about half as potent as Centrophenoxine in boosting choline and ACh levels.137

Increased acetylcholine activity helps short-term memory, concentration, and learning. 2. Centrophenoxine takes out the cellular trash. Lipofuscin are more commonly known as age pigments.138 They show up as “age spots” or “liver spots” on aging skin. And they hide in cells throughout your body. Including your brain, liver, kidneys, heart, adrenals and nerve cells. Lipofuscin are the product of oxidation of unsaturated fatty acids. They also contain other cellular heavy metal waste like mercury and aluminum. The buildup of this toxic mess is caused by a breakdown of your normal cellular waste disposal function. Centrophenoxine helps remove lipofuscin from brain cells. And from cells throughout your body. The beneficial effects of Centrophenoxine were observed in several lab studies on older animals. Administration to these animals significantly increased life-span, and it boosted learning ability compared to age-matched controls.139 How Things Go Bad As we get older, our brain chemistry and energy metabolism changes. ↓ Brain cell membranes degenerate from toxic buildup ↓ Memory, recall, reaction time and mood diminish ↓ Acetylcholine levels decline All of these age-related changes are contributing factors to the neurodegenerative diseases of aging. Including Alzheimer’s and dementia. But even if you’re not concerned with anti-aging, Centrophenoxine may be of some help. Centrophenoxine benefits Centrophenoxine is one of the oldest and most studied nootropics available today. It was developed in France in 1959. Primarily in the search for something to combat age-related cognitive decline. Centrophenoxine is a combination of pCPA and DMAE. Studies show that DMAE can boost choline levels by inhibiting the use of choline by other tissues. But there’s very little evidence that it can cross the blood-brain barrier. pCPA seems to solve that transport problem. Centrophenoxine is water-soluble and quickly enters your brain after you take it. Once in your brain, it boosts signal transmission, and protects neurons. Centrophenoxine gets to work right away boosting available choline. And it gets busy clearing cells of free radicals and lipofuscin. How does Centrophenoxine feel?

Centrophenoxine offers a gentle brain energy boost when you take it first thing in the morning. You’re able to remember things a little easier. Recall when you need it seems effortless. Centrophenoxine works well stacked with Aniracetam, Noopept, and Piracetam. It may provide some of the extra acetylcholine racetams demand when you take them. And if you dose half in the morning, and the other half early afternoon, you should feel a brain energy boost throughout your day. The Research Centrophenoxine Relieves the Symptoms of ADHD A prescription form of DMAE called Deanol was used in the 1960’s and 70’s to treat learning and behavioral problems in children. What’s now known as ADHD. A 3-month, double-blind, placebo-controlled trial involving 74 children was conducted in 1975. They were split into groups and given 40 mg. of Ritalin or 500 mg of Deanol (DMAE). Positive results from this trial showed DMAE comparable to Ritalin in effectiveness in controlling ADHD.140 Centrophenoxine is Anti-Aging Centrophenoxine is not only an effective cognition booster, it helps reverse the effects of aging in your brain. Much of brain cell membrane is made of phospholipids (fat). And it oxidizes as we age. In other words, free radicals build up. And are not removed from cells efficiently the older we get. Aging brain cells also get clogged up with lipofuscin. Lipofuscin are the product of oxidation of unsaturated fatty acids. They also contain other cellular heavy metal waste like mercury and aluminum. You see lipofuscin show up as ‘age spots’ on older skin. The same thing happens in your brain. Studies have shown that Centrophenoxine helps ‘flush out’ free radicals and lipofuscin from brain cells.141 And used by younger neurohackers, helps this cellular waste from building up in the first place.142 Researchers in Hungary conducted a double-blind clinical trial with 50 people suffering from dementia. Average age was 77 years. They gave one group 2 grams of Centrophenoxine for 8 weeks. They found that Centrophenoxine rehydrated ‘intracellular mass’. Proving this compound as a powerful free radical scavenger. It removed free radicals from aging brain cells. And restored them to a healthy state.143 In another study in India, researchers worked with male Wistar rats aged 4, 8, 16 and 24 months. They used these ages because they correlate with human aging from young to elderly. Just like in humans, lipid oxidation and lipofuscin concentration increased with age. The experiment also showed that cellular free radical damage and lipofuscin buildup happened at the same time. This buildup of cellular waste contributes to age-related decline in neuronal electrical activity (neural signaling). Cognition, memory and learning are all affected. The research team found that

Centrophenoxine had no effect on younger rat brains. But in the two older age groups they saw a significant decrease in lipid oxidation and lipofuscin concentration. Showing conclusively the anti-aging action of Centrophenoxine.144 Centrophenoxine Improves Memory Centrophenoxine boosts neuronal glucose and oxygen uptake in the brain. And helps the production of RNA and protein. RNA is derived from DNA in the cell nucleus. And enable neurons to form proteins. Which help encode memory and repair damage to brain cells. In one double-blind clinical trial, researchers worked with 50 people suffering from ‘dementias of medium level’. They gave the group 2 grams of Centrophenoxine, or a placebo for 8 weeks. 48% of the group that received Centrophenoxine showed improvements in memory.145 Another study was made of the effects of Centrophenoxine on the learning and memory of old mice. One group of mice were treated for 3 months and the other group received a placebo. The treated animals showed a significant improvement in memory and learning.146 Dosage Notes Centrophenoxine dosage is typically 500 mg to 1 gram daily. If you’re stacking it with a racetam, split your dose. So a 1-gram dose would be 500 mg first thing in the morning, and the other half early afternoon. Centrophenoxine seems to help increase choline and possibly acetylcholine synthesis in the brain. But keep this in mind; Centrophenoxine and DMAE are related to choline. They are not the same as choline. Some neurohackers insist it should not replace a regular choline source like Alpha GPC or CDP-Choline. And I agree with this observation. Centrophenoxine can be stacked with a choline source. And yet some neurohackers take Centrophenoxine as a choline source to include in their racetam stack. Or use it as a nootropic on its own. Experiment and see what works best for you. YMMV. Side Effects Centrophenoxine has been used as a nootropic for nearly 50 years. So it’s safety is well established. It’s non-toxic and should be well tolerated by most neurohackers. Some reported side effects include stomach upset, body odor, drowsiness, confusion, increased blood pressure, moderate depression, and irritability.147 If you deal with epilepsy or bipolar disorder you should avoid Centrophenoxine entirely. Centrophenoxine may boost acetylcholine in some people. So an excess of acetylcholine could cause the above-mentioned side effects. Cycling Centrophenoxine with 5 days using it, and a 2-day break should eliminate any acetylcholine toxicity.

Available Forms Centrophenoxine comes in powder form and capsules. Capsules are typically 250 – 400 mg. Centrophenoxine is water-soluble so it’s not necessary to take it with a fat or oil. You may find it absorbs better or more quickly when taken with food. Nootropics Expert® Recommendation Centrophenoxine 500 – 1,000 mg per day. I recommend using Centrophenoxine as a nootropic supplement but with some reservation. Your body does not make Centrophenoxine on its own. And it’s not available from food. This nootropic is a combination of DMAE and pCPA and is only available in supplement form. In some countries Centrophenoxine is prescribed as Lucidril® for treatment of Alzheimer’s or agerelated cognitive decline. Studies show Centrophenoxine helps stop or reverse brain degeneration by clearing out free radicals and lipofuscin from brain cells. Making Centrophenoxine one of the primary anti-aging nootropics. Centrophenoxine may also boost acetylcholine synthesis in your brain for some people. Boosting cognition, memory, recall and learning. But this nootropic is NOT a good source of choline to make acetylcholine for most neurohackers. We have much better options for precursors to acetylcholine. Including nootropics like Alpha GPC and CDP-Choline. If you are going to try Centrophenoxine, I suggest starting with a dose of 500 mg daily. Possibly more depending on your racetam usage. Age-related cognitive disorders like Alzheimer’s may want to up the dose to 2,000 mg per day.

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Coluracetam Coluracetam has been shown to boost long-term & working memory, relieve depression & anxiety, and enhance color & sound perception Coluracetam (BCI-540, or MKC-231) is a fat-soluble nootropic in the racetam-class of compounds. Coluracetam is much more potent than the original racetam, Piracetam. Coluracetam was patented by Mitsubishi Tanabe Pharma of Japan in 2005. Making it one of the newest racetam-based nootropics. The patent for coluracetam was later sold to BrainCells, Inc. in San Diego, California. BrainCells is a small, privately-held biopharmaceutical company specializing in developing compounds for the treatment of major depressive disorder (MDD), treatment resistant depression (TRD), and Alzheimer’s Disease. Coluracetam is similar in structure to Piracetam. And like all racetam nootropics, has a pyrrolidone nucleus at its core. The latest clinical research indicates potential for treating depressive disorders, and retinal and optic nerve damage. Coluracetam is a very strong choline targeting supplement. It boosts your brain’s choline conversion to acetylcholine (ACh) through the high affinity choline uptake (HACU) process. Which increases alertness, attention to detail and memory.148 Some research, and personal experience shows Coluracetam may affect AMPA receptors.149 Making it a potential ampakine nootropic. Which could explain the stimulant-like effects without the side effects of traditional stimulants. Coluracetam also shows some anxiolytic (anti-anxiety) qualities helping improve mood and quieting anxiety. Neurohackers who have tried Coluracetam say it helps increase attention span, alertness and boosts long-term memory. Coluracetam vs. Piracetam: What’s the Difference? Piracetam, the original racetam that started the nootropic movement, is a cyclic derivative of GABA. It affects the neurotransmitter acetylcholine (ACh) by helping ACh receptors accept or be more sensitive to acetylcholine. Coluracetam also boosts acetylcholine in the brain. But through a different mechanism of action. Rather than making the ACh receptors more sensitive to ACh, it actually increases the synthesis of acetylcholine from choline. By affecting the high affinity choline uptake (HACU) process. How does Coluracetam Work in the Brain? Coluracetam boosts brain health and function in several ways. But two in particular stand out.

1. Coluracetam boosts your brain’s choline uptake by targeting and working with the high affinity choline uptake (HACU) process in the brain’s neurons. Acetylcholine (ACh) is made up of choline and acetate. These must be available to the neuron terminal at all times. So that ACh can be synthesized whenever it is needed. Free choline circulating in the blood crosses the blood-brain barrier. And is taken up by cholinergic neuron terminals. It gets taken into the neuron by the high affinity choline uptake (HACU) system.150 The synthesis of ACh takes place in the synaptic cleft. The space between neurons as it travels into the neuron. The HACU system is temperature-, energy-, and sodium-dependent. This system is the primary means by which choline needed for the synthesis of ACh is transported into the neuron. And is the rate-limiting step in the production of this critical neurotransmitter.151 When this system breaks down or doesn’t work as efficiently as it was designed, you experience problems with memory, learning, and brain fog. Coluracetam affects this process and helps it work more efficiently. In fact, it seems to boost the HACU process. Even in damaged neurons. Increased acetylcholine in neurons helps improve memory, boosts cognition and provides better decision-making capabilities. 2. Coluracetam also seems to improve AMPA potentiation. AMPA receptors are affected by glutamate. Which works in the brain and central nervous system to improve alertness and cognition. Coluracetam works with both AMPA potentiation and choline uptake enhancement. This combination seems to help improve mood disorders without affecting serotonin levels. Serotonin Reuptake Inhibitors (SSRIs) is the current preferred mainstream medical method for dealing with mood disorders and depression. They come with a list of detrimental side effects. And don’t work for every depressed patient. Researchers reported that Coluracetam was beneficial in treating major clinical depression and anxiety disorder.152 Without affecting serotonin levels in the brain. And without the side effects that go with disrupting serotonin. How things go bad As we get older, our brain chemistry and energy metabolism changes. ↓ Brain cell membranes degenerate ↓ Recall, reaction time and mood diminish ↓ Conversion of choline to acetylcholine breaks down

↓ Acetylcholine levels decline All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Coluracetam can help mood disorders and age-related cognitive decline. But it works as well for the student looking to do better in school. By boosting acetylcholine and controlling glutamate in the brain. Coluracetam benefits Research from a very limited number of studies have shown that Coluracetam will: • • • • • • •

Restore the synthesis of acetylcholine Restore long-term memory Improve working memory Relieve symptoms of severe depression Treat symptoms of general anxiety Increase choline uptake even in damaged neurons Repair retinal and optical nerve damage

The benefits from supplementing with Coluracetam seem to be long-lasting. Even after supplementation has stopped. How does Coluracetam feel? Even with very small doses of Coluracetam you should experience a decrease in anxiety and improved mood. Overall energy levels should go up. Unlike the effect commonly produced by stimulants, Coluracetam offers a more relaxed, calm and freeminded kind of thought-processing. Coluracetam acts quickly to boost long-term and working memory and word-recall. And many nootropic-users report that colors are crisper, or enhanced. Sound and audio seems to wash through you. Some even report that Coluracetam enhances meditation. There is an extremely pleasant sense of being at peace with the world. The Research Coluracetam was first discovered the late 1990’s. And because it’s so new, very few clinical trials have been done with humans. Most of the clinical research available to us has been done on animals. BrainCells, Inc., who acquired the patent from the company that first developed Coluracetam, have begun human trials. Here we have two examples of the clinical research done in the last 15 years on animals. Coluracetam Provides Long-lasting Cognition Improvement Researchers in Japan worked with rats whose memory was chemically impaired. In this study, rats were

dosed with Coluracetam (MKC-231) for 8 days. The team studied the effects on the high affinity choline uptake (HACU) system of the rats after 8-days of repeated Coluracetam treatment. They reported an increase of HACU activity along with a boost in cognition. And concluded that Coluracetam “could induce long-lasting pro-cognitive effects by changing the choline transporter regulation system”.153 Coluracetam Improves Working Memory A study at Iwate Medical University in Japan was done on mice with working memory deficits. In this study, scientists found that Coluracetam improved working memory at all doses tested. They found it significantly reversed an acetylcholine deficit. And concluded that Coluracetam improved memory deficits by boosting high affinity choline uptake (HACU), and the release of acetylcholine.154 Dosage Notes Recommended Coluracetam dosage is 20 - 80 mg per day. So 20 mg would be taken in two 10 mg doses. One Coluracetam dose in the morning, and one in the early afternoon. Higher doses of Coluracetam are based on clinical trials mostly done on animals. When first adding Coluracetam to your stack, most neurohackers start out with a much smaller dose. And see how you react to it. Coluracetam is typically sold in powder form. Smaller doses are often taken sublingually for faster and better absorption. Since Coluracetam is a fat-soluble nootropic, you should take it with a meal containing healthy fats. Or with a tablespoon of extra virgin, expeller cold-pressed coconut or olive oil. Or other similar healthy fat to ensure quick absorption. Side Effects Coluracetam non-toxic. So is considered well-tolerated and safe. Many first-time users of Coluracetam report fatigue which is often the result from starting with too high a dose. Remember, Coluracetam works by enhancing choline uptake in your brain. Choline is a precursor to the production of acetylcholine. If not enough choline is available in your system, you’ll feel the side effects. Side effects are rare but can include anxiety, fatigue, headaches, nervousness and nausea. Again, side effects are often a result of unusually high doses of the nootropic. Headaches from using Coluracetam typically happen when you forget to combine it with a good choline supplement. Headaches are often a symptom of a choline deficit in your brain.

Available Forms Coluracetam is usually sold in powder form. A couple of companies offer it in a liquid base making it easier to dose and take sublingually. Nootropics Expert® Recommendation Coluracetam 20 - 80 mg per day I recommend using Coluracetam as a nootropic supplement. Your body does not make Coluracetam on its own. So to get its benefits you must take it as a supplement. Coluracetam is unique among racetams because it is a high affinity choline uptake (HACU) enhancer. Coluracetam is especially helpful for restoring long-term memory, boosting cognition and better decision-making. All benefits associated with improved choline uptake into neurons. And the improved synthesis of acetylcholine. Coluracetam also has a strong, albeit brief history of treating major depression. For the healthy neurohacker you’ll get the benefit of a sense of contentment and peace. And as an added bonus, the extra choline activity affects optic nerves. So you may experience enhanced colors and sound. The positive effects of Coluracetam appear to be at least semi-permanent. The benefits continue even after it leaves your system. You should use Coluracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost acetylcholine synthesis, so demands the presence of more choline in your brain. Clinical trials say you can safely boost daily intake of Coluracetam to 200 mg. for major depressive disorder if needed. But I suggest starting with 20 mg per day. And increase your doses only after you see how it works in your system.

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Coenzyme Q10 (CoQ10) Coenzyme Q10 helps create ATP within mitochondria in your brain cells. Boosting energy, cognition, memory and recall Coenzyme Q10 (CoQ10) (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinoneis) a natural antioxidant synthesized by your body. It’s also known as “ubiquinone” because it is ‘ubiquitous’ in the human body. CoQ10 is used by every single cell. Your body uses CoQ10 faster than it can produce it. So you need supplemental CoQ10 either from food or a supplement. You can get CoQ10 from eating fatty fish, beef, poultry, nuts, seeds, and oils. CoQ10 contributes to your cell’s source of energy. It helps create ATP within your mitochondria by taking fat and other substances and converting them into usable energy. Brain cells have a higher concentration of mitochondria than most other cells in your body. These mitochondria are like little power plants inside each cell. They even have their own DNA. The source of life and death for neurons lies in mitochondria. Without healthy mitochondria, the natural function of each cell is damaged. And the life of that cell can come to a premature end. Research shows CoQ10 prevents oxidative damage in your brain. Protecting the health of your brain cells.155 CoQ10 is a powerful antioxidant. It protects your cells from free radical damage. Free radicals are oxygen atoms missing electrons. This makes them highly reactive which wreaks havoc in your tissues and DNA. Oxidative damage has been implicated in several neurodegenerative diseases including Alzheimer’s, Parkinson’s, Huntington’s, and Lou Gehrig (ALS) disease.156 Coenzyme Q10 is used throughout your body. It helps produce energy for your cells, boosts heart health, helps maintain healthy blood pressure and immune system, and reduces the signs of aging. Here we’re talking about how CoQ10 affects your brain health and chemistry. CoQ10: Ubiquinone vs. Ubiquinol: What’s the Difference? Coenzyme Q10 (CoQ10) is a fat-soluble nutrient produced naturally in your body. The highest concentration of CoQ10 is in organs that require the most energy – including your heart, liver, muscles, kidneys, and brain. CoQ10 is in the mitochondria in your cells. This is where cellular energy occurs. It acts as an electron acceptor or donor in the chain of reactions that lead to cellular energy production. When oxidized CoQ10 (ubiquinone) accepts an electron from another molecule in the chain, it becomes Ubiquinol. And when Ubiquinol donates an electron, it becomes ubiquinone. This state of equilibrium is necessary and how your body benefits from CoQ10.

The chemical difference between ubiquinone and Ubiquinol is the Ubiquinol compound contains two hydroxyl groups. This makes it more “hydrophilic”, or easier to dissolve in water. And makes it more bioavailable than ubiquinone.157 In Ubiquinol-form, CoQ10 has the ability to scavenge free radicals in the mitochondria and cell membranes. Sites where free radicals inflict the most damage. Supplement makers have been pushing the Ubiquinol form of CoQ10. They claim it’s the best form because it’s what your body produces naturally. They say it’s absorbed up to 8-times better than other forms of CoQ10. Real world use however, does not always back up the marketing claims. Some people say they feel fatigue when using Ubiquinol. And only energy when using ubiquinone. You’ll have to experiment and find out what works the best for you. Your body can use both. But ubiquinone is far less expensive than Ubiquinol. How does CoQ10 work in the brain? Coenzyme Q10 boosts brain health in several ways. But two in particular stand out. 1. When you supplement with enough CoQ10, you’re giving your brain cells the fuel it needs to produce adenosine triphosphate (ATP). ATP is the fuel created within mitochondria in your neurons. Mitochondria are the source of life and death for neurons. They generate your neuron’s energy and control its death. But mitochondria tend to develop defects as we age. As these defects accumulate, mitochondria start to malfunction. This results in a reduction in cellular energy production. And cells die. The result of this dysfunction can be brain fog, cognition problems, poor memory and recall. And ultimately neurodegenerative diseases like Alzheimer’s, Huntington’s, stroke and others.158 Studies show that CoQ10 protects against this cellular damage by raising energy levels. In a study with rats, scientists put CoQ10 in their chow for 10 days before giving them a toxin that caused brain lesions. CoQ10 reduced lesions by 30%. And restored energy production in neurons to nearly normal levels.159 2. CoQ10 preserves brain function and fights mental illness and migraines. CoQ10 is essential not only in preventing brain deterioration at a structural level, but in maintaining normal function at all ages. Studies are beginning to show some troubling associations between migraine headaches and mental health issues like depression and schizophrenia. Scientists don’t know for sure what causes migraines. But think it may be related to brain energy levels. Studies show that CoQ10 supplementation in children, adolescents and adults had significant decreases in frequency and length of migraines.160

Major depression, bipolar disorder and schizophrenia have long been considered separate health issues. Lately, they are being recognized as having mitochondrial dysfunction in common. And higher oxidative stress levels.161 Just one of many studies show that depression in older bipolar adults had a significant reduction in symptoms. This was after treatment with 1,200 mg of CoQ10 per day.162 How things go bad As we get older, the chemistry in our brain cells and energy metabolism changes. ↓ Brain cell membranes degenerate ↓ Recall, reaction time and mood diminish ↓ Neurotransmitter levels decline All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. But even if things haven’t degenerated to such a debilitating level, CoQ10 can help. CoQ10 benefits Research from thousands of studies have shown that Coenzyme Q10 will: • • • • • • •

Boost energy levels and stamina Reduce fatigue Reduce the possibility of age-related diseases Lower blood pressure Lower blood sugar levels Provide protection and energy to your brain Boost cerebral blood flow

How does CoQ10 feel? Optimizing your mitochondria is one the most powerful strategies you have to extend your life. Mitochondrial dysfunction is associated with the aging process, including many age-related diseases. So when taking CoQ10 you should feel better and more energized. Thinking should be clearer. Less fatigue and stamina improved. Some neurohackers report feeling more fatigue while taking Ubiquinol. And actually feel better taking the less optimized form ubiquinone. The Research CoQ10 was first isolated from beef hearts at the University of Wisconsin in 1957. Research continued at Merck & Company, Stanford Research Institute, and the University of Texas at Austin. Many studies

from around the world have been published since.163 CoQ10 can Improve Learning A study at the University of Texas was conducted to find out if supplementing with CoQ10 or Vitamin E could help older mice learn tasks more quickly. The researchers separated groups of older mice. And gave each mouse either CoQ10, Vitamin E, or both antioxidants for 14 weeks. The mice were run through a battery of tests assessing learning, memory and psychomotor function. The study concluded that CoQ10 combined with Vitamin E working in concert boosted performance in all tests.164 CoQ10 Improves Memory Neuron death caused by oxidative stress is implicated in a host of neurodegenerative diseases. Including Alzheimer’s, Parkinson’s and stroke. Oxidative stress is an imbalance between the production of free radicals, and the ability of your body to detoxify the harm caused by free radicals. Exposure to toxins in your everyday environment can cause oxidative stress. Researchers at the University of Windsor in Canada demonstrated this effect using human cells in the lab exposed to an herbicide commonly used in North America. Your brain exposed to this toxin causes apoptosis (programmed cell death) and DNA fragmentation. But scientists found that cells pretreated with CoQ10 prevented oxidative stress and neuron damage.165 CoQ10 Reverses Gulf War Illness The profound protective effect of CoQ10 on brain neurons and memory was proven in studies with soldiers who fought in the Persian Gulf War. About one-third of the 700,000 troops deployed during the first Persian Gulf War, have been diagnosed with Gulf War Illness (GWI). Symptoms include fatigue, muscle pain, weakness, and decreased cognitive function. Gulf War Illness was caused by exposure to pesticides, sarin nerve gas, and other toxins during the war. Forty-six United States Gulf War veterans participated in this randomized, double-blind, placebocontrolled study. All had been diagnosed with GWI. The veterans were given CoQ10 in pill form, or a placebo for 3 ½ months. Researchers concluded that 80% of those receiving only 100 mg of CoQ10 during this study saw improvements with headaches, irritability, recall and muscle pain. The degree of improvement correlated to the degree in which CoQ10 levels in the blood increased.166 Dosage Notes CoQ10 can help the mitochondria in your brain, and throughout your body, work more cleanly and

efficiently. It reduces oxidative stress and damage to mitochondria. Helping to slow the aging process. Dosing CoQ10 depends on what you’re trying to accomplish. Generally dosing for a healthy adult is 30 – 400 mg daily. • • • • • • • • • •

As an antioxidant: 60 – 150 mg daily Muscle control problems: 300 – 3,000 mg daily Alzheimer’s Disease: 400 mg daily Heart Attack recovery: 30 – 600 mg daily To prevent heart disease: 200 mg daily Chemotherapy side effects: 50 – 90 mg daily Improve exercise performance: 50 – 300 mg daily Male infertility and Peyronie’s disease: 30 – 300 mg daily Diabetic nerve pain: 400 mg daily Weight loss: 100 mg daily

Note: recommended dosing is for as long as you have symptoms. Work with your doctor and get tested for CoQ10 levels in your blood. Once your CoQ10 level are optimized you can scale back to a maintenance dose. Side Effects The primary “side effect” of using CoQ10 in your nootropic stack is - you’ll feel better. You should have more energy and thinking should be clearer and faster. CoQ10 may reduce the toxic effect of some chemotherapy drugs. And it may enhance the effectiveness of some blood pressure medications. Which can be good or bad depending on your situation. CoQ10 can reduce the efficacy of a blood thinner like Warfarin. It can also lower blood sugar levels. So needs to be monitored if you have diabetes. Caution is advised when using CoQ10 with aspirin. Especially if you have a bleeding disorder. Talk to your doctor if you’re on any medication before you start using CoQ10. A few people who use CoQ10 report rashes, nausea, abdominal pain, dizziness, sensitivity to light, irritability, headache, heartburn or fatigue. Some neurohackers say they feel fatigue when using Ubiquinol but not with the less expensive Ubiquinone. Experiment and see what works best for you. Available Forms There are two types of CoQ10 used in CoQ10 supplements: ubiquinone and Ubiquinol. Some alternative health practitioners advise staying away from ubiquinone because your body has to convert it to Ubiquinol to use it. If you’re under 25 and in good health, you can likely get the benefit of CoQ10 with the less expensive

ubiquinone. Over 25 and you’re better off with Ubiquinol. Ubiquinol is identical to 95% of the CoQ10 your body is designed to naturally produce. Which means your body doesn’t have to convert the CoQ10 to use it. Some in vitro research shows that Ubiquinol is up to 8-times more bioavailable than other CoQ10 supplements. (“8-times” is likely a bit of an exaggerated marketing claim). CoQ10 comes in liquid and capsule form. Logic says the liquid form is easier to absorb by your body. Nootropics Expert® Recommendation Coenzyme Q10 200 – 400 mg per pay I recommend using CoQ10 as a nootropic supplement. Your body does make some CoQ10 on its own. And from the food you eat. But studies have shown we don’t get an adequate supply of CoQ10 from food sources in our diet. CoQ10 is especially helpful for those suffering from age-related cognitive decline. Studies show it helps stop or reverse brain degeneration with Alzheimer’s Disease, and other cognitive disorders. In any stage of the disease. I suggest starting with a dose of 200 mg daily. And CoQ10 is a great compliment to a stack with any nootropic. You need to provide your brain mitochondria create the fuel your brain cells are demanding. Or neurons start to break down from the inside. Signs that your lacking adequate CoQ10 is brain fog, slow thinking, headaches and muscle aches. Age-related cognitive disorders that include muscle control problems may want to up the dose to 3,000 mg per day. But for a limited time until CoQ10 blood levels are stabilized. Work with your doctor.

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Creatine Creatine has been shown to boost cognition and prevent mental fatigue Creatine is one of the most effective cognitive enhancers available. This non-essential amino acid is synthesized in your liver, kidneys and pancreas. And used in your brain to re-charge the Adenosine Triphosphate (ATP) produced within mitochondria in brain cells. Creatine is stored in your body as creatine phosphate, or phosphocreatine. And is critical for producing Adenosine Triphosphate (ATP) in the mitochondria of your brain cells. Here’s how it works… ATP is the primary energy molecule used in your cells as energy. ATP is your body’s natural fuel source. ATP is broken down to produce biochemical energy throughout your body. Including in your brain cells. During this biochemical process, ATP loses one of its phosphate molecules. And is changed to adenosine diphosphate (ADP). This is where creatine steps in. Remember, creatine is stored in your body as creatine phosphate. It re-charges ADP by donating a phosphate molecule to ADP. Which produces more ATP that can be used to make more energy. Without creatine to re-charge ATP, your brain’s cells are literally starved for energy. Creatine Monohydrate vs. Buffered Creatine vs. Creatine Ethyl Ester: What’s the Difference? It’s easy to get confused by the many forms of creatine available. And how to know which one works best in your nootropic stack. Well, let’s get past all the marketing hype, and settle this now. Creatine is one of the most well-researched supplements in the world. Thanks in large part to the sportsnutrition world. Creatine monohydrate is the form used in most of the clinical studies on creatine. It’s the gold standard of creatine. And has been proven over decades of use. Buffered creatine is marketed as being able to outperform creatine monohydrate because of its higher pH level. But research does not back up this claim. Researchers in the Exercise and Sport Nutrition Laboratory at Texas A&M University conducted a double-blind study with 36 resistance-trained athletes. They tested creatine monohydrate (Creapure®) against buffered creatine (Kre-Alkalyn®). Following manufacturer’s directions for loading and maintenance phases. And ran the trial for 28-days. The research team concluded there was no evidence that supplementing with a buffered form of creatine resulted in fewer side effects. Or that the buffered form was more efficacious and/or safer than creatine monohydrate.167

Creatine Ethyl Ester is another form of creatine that is supposed to convert back to usable creatine once in your body. It’s marketed as having better absorption than creatine monohydrate. But the research shows it’s actually less effective. Because once in your body, it’s converted into an inactive form called “creatinine”.168 The bottom line is don’t overpay for fancy forms of creatine. No matter how good the marketing hype. Creatine monohydrate is still the least expensive and most effective form of creatine available today. How does Creatine Work in the Brain? Creatine boosts brain health and function in several ways. But two in particular stand out. 1. Creatine levels linked to optimal memory ability and retention. One study at the University of New Mexico investigated working memory ability. Or the brain’s ability to hold information for future use. Scientists studied children’s brains aged 7 through 12 using magnetic resonance spectroscopy. And measured various brain neurochemicals. The study found that children with the highest levels of creatine in their brain had a better working memory. And concluded, “… we speculate that higher resting creatine levels may allow for greater intask activation [and] facilitate processing.”169 2. Creatine reduces mental fatigue. Another study published in Neuroscience Research examined the effects of supplemental creatine on mental fatigue. 24 healthy adults participated in this double-blind, placebo-controlled study. In this study, the adults who took 8 grams of creatine daily for 5-days showed significantly less mental fatigue while performing math than those who took no creatine.170 The research team said that creatine appeared to help increase oxygen utilization in the brain. How things go bad ATP and creatine are critical to brain function. If you don’t have adequate creatine to recharge ATP, your brain can’t function at its best. And certain genetic disorders can interrupt brain creatine metabolism. Causing significant neurological defects. Lack of ATP and creatine will affect neuron repair, and the production and transmission of neurotransmitters. If a creatine deficiency is caused by a genetic defect early in life, it can result in developmental delay, mental retardation, speech disabilities and muscle weakness. ↓ Cognition, memory, recall, reaction time and mood diminish ↓ Brain cell membranes degenerate

↓ Neurotransmitter levels decline ↓ Mental health, language and fine motor skills decline171 All of these changes in brain energy metabolism are contributing factors to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, ALS, epilepsy, and dementia. But even if you’re not concerned with genetic defects, or the effects of aging, Creatine can help. Creatine benefits Study after study shows that creatine supplementation has a significant impact on working memory and intelligence. Both tasks that require mental speed of processing. Creatine supplementation plays a major role in brain energy capacity. And influencing brain performance. You may find it curious that researchers who study cognition and athletic performance seem to favor using vegetarians and vegans. And giving them creatine supplements. They use vegetarians as test subjects because creatine is only found in animal flesh. And vegetarians don’t eat meat. Creatine is not an essential amino acid because we can synthesize it from other amino acids. But amino acids found in plant foods are not synthesized very efficiently. This is the reason why vegetarians have lower creatine levels in their bodies than those of us who eat meat. Our cells run on energy supplied by ATP. We burn ATP energy when using our muscles. But we go through ATP faster when we use our brains. Consider that our brain only makes up about 1 – 3% of our body weight. But the billions of neurons in our brains use 20% of our body’s total ATP-derived energy. ATP energy is used in your brain for neuronal repair. And to produce, package and secrete neurotransmitters. It’s the power behind bioelectrical signals when neurons communicate with each other. During this neuronal activity, ATP loses one of its phosphate molecules. And is changed to ADP. Creatine is needed to recharge ADP by donating a phosphate molecule. So you can use that ATP energy again. This is why every neurohacker should have creatine as part of their nootropic stack. How does Creatine feel? Once you start supplementing with creatine, you should experience improved cognitive function. Thinking will be clearer and faster. Mental energy will get a boost. And you won’t feel mentally wasted after an intense mental workout.

Reading should be easier, and you won’t find yourself re-reading that last sentence or paragraph. Overall, you should feel a boost in both physical and cognitive abilities. And an improvement in your sense of well-being. You’ll feel better! The Research Creatine was identified way back in 1832. And science has been researching it in every way possible since then. Thousands of studies have been done on physical and brain health. And how they’re related to creatine. Creatine Boosts Working Memory & Intelligence A research team at the University of Sydney decided to test the effect of creatine supplementation in 45 young adult vegetarians. People who stick to a vegetarian diet are typically deficient in creatine. Because red meat is a main source of this critical nutrient in our diet. In this double-blind, placebo-controlled trial they gave some of the young adults 5 grams of creatine once a day for 6 weeks. Then they tested for intelligence and working memory performance. The researchers found that creatine supplementation had a significant positive effect on both working memory and intelligence. Both methods that they used to test the subjects required speed of processing. The research team concluded brain energy capacity has a profound influence on brain performance. And that brain energy relies on creatine.172 Creatine Increases I.Q & Attention Span Scientists at the University of Sunderland in the U.K. conducted a double-blind, placebo-controlled study. Working with 34 healthy men and women with a mean age of 21 years. None of the participants were vegetarian. One group took 5 grams of creatine daily for 2 weeks. And the other group took a placebo. They were tested before supplementation. And then after 2 weeks of using either creatine or the placebo. The tests consisted of Memory Scanning, Number-Pair Matching, Sustained Attention and Arrow Flankers, followed by an IQ test. These tests were mentally strenuous by any standard. The researchers concluded that those taking creatine tested much better and showed less mental fatigue than the placebo group. Creatine increased attention span, I.Q, and working memory.173 Creatine Repairs Brain Cells Drugs currently used to treat neurodegenerative diseases like Parkinson’s and Alzheimer’s provide temporary relief of symptoms. But do not stop the underlying cause of the disease. Scientists are now working on therapies that focus on replacing injured and dead brain cells. And boosting growth factor along with other neurotrophic molecules. These new therapies include developing vaccines. And using compounds like creatine to immunize

against these life-threatening diseases.174 One thing scientists know for sure is impaired energy metabolism plays a prominent role in many of these neurological diseases. Recent studies show impaired energy production in the brain causes neuron cell death. Optimal levels of ATP are crucial to maintaining healthy brain cells. And creatine is a critical in maintaining cellular energy levels. Supplementing with creatine has been proven for neuroprotection in a wide range of neurodegenerative diseases. Including Parkinson’s, ALS, Alzheimer’s, stroke and epilepsy.175 Dosage Notes Recommended dosage of creatine for nootropic benefit is 5 grams per day. Studies show that creatine should be consumed with carbohydrates for best absorption.176 The myth that you should not take creatine with caffeine is exactly that – a myth. No reliable study has shown this to be true. Side Effects Creatine is produced naturally in your body. So is considered well-tolerated and safe. But over-consumption of creatine can be hard on your kidneys and liver. These organs are creatine factories. And too much creatine can overwork them. If you are dealing with liver or kidney problems, talk to your doctor before supplementing with creatine. Pure creatine is the safest. But many commercially available creatine supplements contain contaminants. Check the labels carefully. Review the manufacturer’s website and any other material they offer that attests to their quality standards. Other side effects can include mild diarrhea, gas, upset stomach or stomach cramps, muscle cramps, increased urination, headaches, reduced appetite and water weight gain. Usually when using too much creatine. Or during the “loading” phase of creatine supplementation. Because creatine causes an energy boost in many neurohackers, avoid dosing in the evening. Or you may find difficulty getting to sleep. Available Forms The best dietary source of creatine is found in wild game. Other sources include red meat and certain fish. The most common and least expensive form of creatine available as a supplement is in powder form. It’s also available in capsules and a liquid. I recommend skipping all the creatine nitrates, ethyl esters, malate, HCL’s and others – and stick with

creatine monohydrate in powder form. Nootropics Expert® Recommendation Creatine 5 grams per day I recommend using Creatine as a nootropic supplement. Your body does make some creatine on its own. And from the food you eat. But if you’re a vegetarian, or don’t get enough quality creatine in your diet every day, you will benefit by adding creatine to your nootropic stack. Creatine is critical for fueling the activity in your neurons needed for cognition, memory, critical thinking, decision-making and more. Creatine is especially helpful if you’re dealing with fatigue. Or putting unusually high demands on your brain. Resulting in mental fatigue. Studies have shown creatine can help prevent a host of neurodegenerative diseases as well. I suggest a dose of 5 grams daily. It takes a while for creatine to build up in your system. So if you’d like to get the benefits faster, load with 20 grams a day for a week. And then pull back to a maintenance dose of 5 grams daily. And Creatine is a great compliment to a stack including any nootropic from the racetam-family. Anything that causes an increase in uptake of acetylcholine in your brain. And an increase in mental processing. You need to provide your brain with the fuel it demands. And creatine is a proven way to do it.

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DHEA DHEA has been shown to boost cognition, memory, energy levels and motivation. DHEA (dehydroepiandrosterone) is the most abundant natural steroid hormone in your body. It’s sometimes called the “youth hormone”. And is a source of your sex hormones. DHEA is naturally synthesized in your testes, adrenal glands, and brain. It’s a precursor to DHT and testosterone in men, and estrogen in women. And can activate both androgen and estrogen receptors. Besides making DHEA, your adrenal glands also produce cortisol. Which is in direct competition with DHEA for production. When cortisol is high, especially for prolonged periods of time, your adrenal glands wear out. And DHEA production will decline. DHEA can be made in the lab from wild yam and soy. But your body cannot produce DHEA from eating these foods. To boost DHEA you need to take it as a supplement.177 DHEA Declines with Age Your body’s natural production of DHEA varies with age. Low levels are produced before puberty. With peak production in your 20’s. Between ages 25-30 to 75 your DHEA levels will drop by 80%.178 Affecting everything from alertness, memory, recall, and mood to sex drive. Its decline is even implicated in some neurodegenerative diseases. The age-related variation in DHEA production has led scientists to believe that DHEA could be linked to the aging-process itself. Many athletes use DHEA to increase muscle mass, strength and energy. But DHEA use is banned in the U.S. by the National Collegiate Athletic Association (NCAA). It’s also considered a “banned substance” by the NBA, NFL, and United States Olympic Committee. In Canada, DHEA is considered a ‘drug’ and is only available by prescription. Which says something about the power of DHEA. It’s technically a steroid, which may be why it’s included in with Performance Enhancing Drugs (PEDs). In 2007, the U.S. Congress tried to re-classify DHEA as an “anabolic steroid drug”. Which means this natural human hormone would have only been available as a prescription drug. Fortunately, this legislation never passed and you can still buy DHEA as an OTC supplement. Here we’re talking about how DHEA affects your brain health and chemistry. How does DHEA Work in the Brain? DHEA boosts brain health and function in several ways. But two in particular stand out. 1. DHEA boosts working memory. Research has shown that higher DHEA levels are directly

related to concentration, working memory and executive function (decision-making). A study done in Australia in 2003 and 2004 worked with 295 women aged 21 – 77 years. The researchers set out to investigate whether circulating levels of DHEAS (dehydroepiandrosterone sulfate) contributed to cognitive function. The women in the study went through a comprehensive battery of tests for cognitive function, and DHEAS levels. The researchers concluded that, “Higher endogenous DHEAS levels are independently and favorably associated with executive function, concentration, and working memory.”179 Note: DHEAS is simply DHEA that is produced with the addition of a sulfate group. Naturally produced in your body, it produces the hormone estrone. DHEAS can be back-converted in the body to DHEA, and both are often simply referred to as DHEA. 2. DHEA enhances mood - naturally. DHEA has been found to improve both mood and energy while alleviating depression. DHEA may be a good natural alternative to traditional antidepressants. A double-blind, randomized, placebo-controlled study was done at the U.S. National Institutes of Health with 46 men and women. The study subjects had been diagnosed with major or minor depression. The depressed patients went through 6 weeks of DHEA therapy. 90 mg per day for 3 weeks and 450 mg per day for 3 weeks, and 6 weeks of placebo. They were then tested using two different Depression Rating scales, and for sexual function. The study found that DHEA offered a significant improvement in depression symptoms. And major improvements in sexual function. In a very rare admission from the conservative National Institutes of Health, “We find DHEA to be an effective treatment for midlife-onset major and minor depression.”180 How things go bad: As we get older, our brain chemistry and energy metabolism changes. ↓ Concentration, working memory and executive function decline ↓ Neuron receptors degenerate ↓ Adrenals wear out and DHEA levels decline ↓ Appetite regulation, energy and alertness decline All of these age-related changes are influenced by declining DHEA levels. And are contributing factors to neurodegenerative diseases and depression. DHEA levels are an inevitable consequence of aging. And can contribute to the onset of degenerative disease.

DHEA benefits The latest scientific research validates what we know of DHEA’s anti-aging effects. And it’s not just for athletes. DHEA’s neuroprotective benefits are vital to memory and improving mood. DHEA supports cardiovascular health and activates genes that prevent cardiovascular health problems, diabetes and obesity. It boosts quality of life and sexual function. It even improves the appearance of younger-looking skin. DHEA supplementation can enhance cognitive function and memory, and improve decision-making (executive function). It’s even been shown to decrease brain cell death and promote general cerebral health.181 How does DHEA feel? You should experience a noticeable increase in motivation and drive soon after supplementing with DHEA. Especially if your levels are low. If you are under constant stress, have chronic fatigue, feel weak, depressed or have a low sex drive – find a Naturopathic practitioner. And have your DHEA levels checked. Too many neurohackers suffer unnecessarily from high stress and low DHEA production. Don’t be one of those people. The Research DHEA is a steroid hormone and has a strong influence on both brain structure and function. Social and physical stress has severe negative effects in your hippocampus. Affecting memory and orientation. DHEA seems to have a neuroprotective role in reducing the toxic effects of glutamate and cortisol elevated by stress. Studies show low DHEA levels in people suffering from major depression. And that if cortisol and DHEA are out of balance it will delay recovery from these diseases. DHEA plays a role in the treatment of depression. Whether its caused by stress or aging. It affects both the cellular structure of the brain and its function.182 DHEA Levels Predict How Long You’ll Live Scientists in Japan set out to determine if DHEA levels could predict longevity. The study included 948 men and women aged 21 – 88 years. The researchers measured DHEAS levels at the beginning of the study. And periodically for the next 27 years. DHEAS levels were higher in the men than women as expected. DHEA levels were measured along with blood pressure, and blood sugar. Of the three health measures, DHEAS levels in men were the strongest predictor of longevity. It doesn’t matter what your age, blood pressure or blood sugar levels.183 This 27-year study concluded that DHEAS levels could be a way to predict how long you’ll live.

DHEA Improves Memory Studies in rodents showed DHEA improved cognition. But there were inconsistent findings in humans tying cognition to DHEA supplementation. So scientists at the University of Newcastle upon Tyne in the U.K. decided to find out for themselves. In this double-blind study, 24 healthy young men were treated with 150 mg per day of DHEA for 7days. Mood, memory and the stress hormone cortisol were measured. Including scanning their brains to identify brain regions involved in cognition. The study results showed a reduction in evening cortisol concentrations. And improved memory and mood. Recall significantly improved. And the researchers concluded this study was the first to show that DHEA had a beneficial effect on memory in healthy young men.184 DHEA Levels Associated with Mood in Pro Golfers Several studies suggest that DHEAS levels drop following different types of acute stress. Implicating DHEA’s role in coping with stress and recovering from stress. Researchers in Taiwan wanted to find out what happened to DHEA levels during a negative outcome in an athletic competition. In this case, they studied 14 elite golfers participating in a major national golf tournament. The golfers were divided into 2 groups. One group made the cut during the competition. And the other group did not make the cut. DHEAS levels were measured in both groups 1-day before the competition. And then on days 1, 3 and 5 after the players’ final competition. Study results showed that DHEAS levels in players that made the cut during the competition did not change. Those players that failed to make the cut experienced a drop in blood concentrations of DHEAS. This study suggests that DHEA plays a role in your coping mechanism during psychologically challenging times. Supplementing with DHEA during times of stress could help alleviate some of the symptoms normally associated with high stress levels.185 Dosage Notes Recommended dosage of DHEA is 25 - 50 mg per day. DHEA is a strong steroid hormone. And low supplemental doses affect gene expression in inhibiting metabolic syndrome. DHEA supplementation boosts bone strength and enhances cognition and memory. DHEA supplementation is not recommended for anyone under 18 years old. And like many nootropics, too much DHEA is NOT a good thing. It can lead to problems. Many nootropics users and doctors recommend taking “hormone holidays”. In other words, use DHEA for a month then take a month off. Supplementing with DHEA beyond the normal range may be advisable for short periods of time. Such

as restoring a badly depleted adrenal system. But maintaining large doses of DHEA can lead to unpleasant side effects. Note: If you have been diagnosed with a hormone-dependent cancer, you should not supplement with DHEA until your cancer has been cured. Side Effects Testing for DHEA levels is very important if you’re planning on supplementing with this powerful compound. Because if your hormone levels are normal and you start taking DHEA, you could experience side effects like acne, hair loss, tumor formation, heart arrhythmia, and insomnia. At higher than 100 mg doses, DHEA has been linked to side effects. Many experts caution against highdoses of DHEA. Or long-term usage. Available Forms The most common form of DHEA is in capsule form. Supplement manufacturers offer capsules ranging from 10 – 100 mg. You can even get DHEA as an ointment, lozenge, or cream. Keep in mind that a 25 mg DHEA capsule will not deliver 25 mg of DHEA to your system. It first must pass through your liver where it’s further broken down. Your body is not used to getting hormones through your digestive system. Once swallowed, only 10-15 percent will eventually reach the tissues you are targeting – like your brain. This is why many Naturopathic practitioners suggest using a DHEA cream instead. But here again you have a problem. While more DHEA is bioavailable by using DHEA cream on your skin, some argue there’s even a better way to take DHEA. And that’s by applying the cream to the membranes of your vagina if you are a woman. And in your rectum if you are a man. One other option is to take DHEA sublingually. It makes logical sense that if taken under your tongue, DHEA bypasses your liver. And goes directly into your bloodstream. Personally, I use 25 mg of DHEA in capsule form in the morning, and another 25 mg at noon. And have experienced a considerable boost in energy during the day. But cycling one month on, and a one-month off to give my body a “hormonal holiday”. Nootropics Expert® Recommendation DHEA 25 – 50 mg per day I recommend using DHEA as a nootropic supplement. But with a huge caveat. Get your DHEA levels checked before starting supplementation to be on the safe side. Your body does make some DHEA on its own. But DHEA production inevitably declines with age. And possibly even faster depending on the health of your adrenal glands.

If you are under constant stress, have chronic fatigue, feel weak, depressed, or have a low sex drive – find a Naturopathic practitioner. And have your DHEA levels checked. Too many neurohackers suffer unnecessarily from high stress and low DHEA production. Don’t be one of those people. Maintaining optimal DHEA levels can enhance cognitive function and memory, and improve decisionmaking (executive function). It’s even been shown to prevent brain cell death and boost general cerebral health. Start with 25 mg of DHEA per day. And see how you feel. Increase the dose to no more than 50 mg per day. And watch for side effects. And don’t forget to cycle it. Take it for a month and take one month off.

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DMAE DMAE has been shown to boost alertness, focus, memory, and mental clarity DMAE (Dimethylaminoethanol, Deanol, Deaner) has two methyl groups and is structurally similar to choline. Choline is a direct precursor to acetylcholine (ACh). ACh is a critical neurotransmitter that influences everything from memory to muscle control. And it is the relationship ACh has with DMAE that generates most of the hype around DMAE as a nootropic. But it turns out that DMAE is NOT a precursor to acetylcholine as reported on many nootropic and brain optimization sites. However, many neurohackers report that supplementing with DMAE has worked wonders for their brain. So here we’ll try to clear up some of the confusion and misinformation surrounding DMAE as a nootropic supplement. And if adding DMAE to your stack makes sense. DMAE is an amine naturally produced in small amounts in your brain. High levels of DMAE are also found in seafood like anchovies and sardines. Researchers have speculated that DMAE may increase acetylcholine (ACh) levels in the brain by inhibiting choline metabolism in peripheral tissues. By preventing the use of choline by other tissues (including synthesis into acetylcholine), DMAE increases choline levels in the bloodstream.186 Once DMAE crosses the blood-brain barrier, it increases choline levels in the brain. So with higher choline levels present, you would expect elevated levels of acetylcholine (ACh). But research has shown this is not always what happens when DMAE gets to your brain. In one study, DMAE was rapidly taken into the brain. But when it reached synapses – nothing happened. Choline levels rose but did not convert into acetylcholine.187 What’s going on here? First, we must look at how acetylcholine (ACh) is made. ACh is synthesized in a single step reaction catalyzed by the enzyme choline acetyltransferase (ChAT).188 The rate-limiting steps in ACh synthesis are the availability of choline and Acetyl Coenzyme A (Acetyl-CoA). The only other source of acetylcholine (ACh) is synthetization from phosphatidylcholine (PC) via phosphatidylethanolamine N-methyltransferase (PEMT).189 And this ACh synthesis only happens in cholinergic receptors. So it would appear that DMAE cannot be converted to either choline or ACh. The only way DMAE can increase choline is by inhibiting choline metabolism. And the reason why choline levels rise in the brain when supplementing with DMAE is because the choline does not synthesize into acetylcholine (ACh).190

So why do some neurohackers experience a benefit in increased focus, clearer cognition, and even an antidepressant effect with DMAE? It could be that DMAE stimulates cholinergic receptors into acting.191 And with extra choline floating around because of DMAE, these neuroreceptors may decide to produce some extra ACh.192 DMAE may be useful to those dealing with a choline deficiency in the brain. And studies show that DMAE effectiveness in the brain depends on the health of the cholinergic system in your brain.193 But as neurohackers we have more efficient options available for boosting choline in the brain. Centrophenoxine which is a combination of DMAE and pCPA (parachlorphenoxyacetic acid) seems to boost acetylcholine in the brain much more efficiently than DMAE. How does DMAE Work in the Brain? DMAE boosts brain health and function in several ways. But two in particular stand out. 1. DMAE is a neuroprotectant. Lipofuscin is a cellular waste product that accumulates in brain cells as we age. It’s the same waste product that causes brown spots on skin. Lipofuscin hides in cells throughout your body including your brain, eyes, liver, kidneys, heart, adrenals, and nerve cells (neurons). Neurohackers often report that supplementing with DMAE produces enhanced vision. This vision effect may be DMAE’s ability to help remove waste like lipofuscin from cells that affect vision. This lipofuscin removal mechanism of action by DMAE has been shown in animal studies in the lab. Researchers used Centrophenoxine injections on 17-month old female mice. The animals were injected daily for 3 months. The researchers studied changes in pigment layers of the retina of both eyes in the mice. And found there was significant reduction of lipofuscin pigment in the treated animals.194 Centrophenoxine breaks down into DMAE once in your body. And it is the DMAE in this nootropic that provides the lipofuscin scavenger affects. 2. DMAE enhances attention and mood. DMAE has been reported by some neurohackers to improve vigilance, attention, mood and energy while alleviating depression. A study by German researchers may explain where this feeling of well-being comes from when supplementing with DMAE. This double-blind, placebo-controlled trial used 80 human subjects evenly split between male and female. The study analyzed their brain’s electrical reaction during presentation of five 7-minute video clips followed by a 3-minute pause for each. This procedure was repeated after 6 and 12 weeks of daily intake of DMAE or a placebo. The subjects taking DMAE for 3 months developed significantly less theta and alpha brain waves. Decreases in theta and alpha brain waves have been associated with increased vigilance and attention.

The subjects using DMAE were also more active and felt better. The researchers concluded that DMAE can induce a state of better feeling of well-being.195 How things go bad As we get older, our brain chemistry and energy metabolism changes. ↓ Concentration, working memory and executive function decline ↓ Cholinergic receptors degenerate ↓ DMAE levels decline ↑ Lipofuscin and free radicals build up in brain cells All of these age-related changes could be influenced by declining DMAE levels. And are contributing factors to neurodegenerative diseases and depression. DMAE levels are an inevitable consequence of aging. And may contribute to the onset of degenerative disease. DMAE benefits DMAE increases choline levels in your brain. This increase in choline and DMAE’s ability to stimulate cholinergic receptors into action may lead to an increase in acetylcholine (ACh) levels. But DMAE does not directly elevate acetylcholine levels in the brain. DMAE is NOT a precursor to acetylcholine.196 Increased ACh levels affect learning and memory. ACh helps the encoding of memories and your ability to concentrate. As neurohackers, we absolutely want to increase acetylcholine levels. Especially if our brain is low on ACh. But DMAE is not the best way to achieve the goal of elevated ACh levels. Research into DMAE is ongoing and there may be some benefits to DMAE supplementation not yet known by the neurohacking or research community.197 DMAE has been used to treat a variety of conditions from cognitive disorders including ADHD. DMAE is also used in skin care products to help reduce age spots, fine lines, and wrinkles, and even sagging skin.198 Free radicals can cause damage to DNA, upset cellular metabolism, and induce the creation of reactive oxygen species that kill brain cells.199 Some research has found that DMAE is a somewhat effective free radical scavenger.200 DMAE has been found to diminish the extent of “cross-linking” of proteins that have been implicated in diseases like Alzheimer’s.201 Researchers think this may be due to DMAE’s effectiveness as a free radical scavenger.202

DMAE is reported to induce lucid dreaming.203 How does DMAE feel? Some neurohackers report that DMAE supplementation causes a noticeable boost in their ability to concentrate. DMAE users often report: • • • • •

better memory (especially short-term memory) mentally alert improved focus mental clarity better sleep patterns

Dosing more DMAE than recommended has been reported to make you feel edgy and tense. And you may experience muscles spasms, particularly in your shoulders and neck. The Research Early DMAE Research A prescription form of DMAE called Deaner or Deanol was in clinical use as far back as the 1960’s and 70’s. Deanol was used for the treatment of learning and behavioral problems associated with shortened attention span. Two clinical trials conducted over 40 years ago proving the efficacy of using DMAE for treating what’s now known as ADHD are below. But in 1983, the FDA in all their wisdom insisted on additional studies to prove the effectiveness of DMAE. And because clinical trials would have been costlier than product sales could support, the company making Deanol and Deaner took them off the market. DMAE is now available as a nootropic supplement. One that your doctor or psychiatrist is unlikely to prescribe to you for treating your ADHD. DMAE to Treat ADHD One double-blind, placebo-controlled study compared the effects of DMAE supplementation with methylphenidate (Ritalin) for treating ADHD. 74 children diagnosed with learning problems and hyperactivity were referred to this study. The children received 40 mg of Ritalin, 500 mg of DMAE or a placebo daily for 3 months. Behavior, reaction times and other psychometric tests were done before and after treatment. Both ‘drugs’ proved to be effective according to several tests. The researchers concluded that DMAE supplementation significantly improved performance in children with learning and behavior disorders.204

Another study conducted by Dr. Carl Pfeiffer of the Brain-Bio center in Princeton, New Jersey with 25 girls and 83 boys found similar results in using DMAE for treating ADHD. In this study, Dr. Pfeiffer found that DMAE enhanced the behavior in 2/3 of the boys and 3/4 of the girls. Attention span was better, irritability and hyperactivity were decreased, scholastic ability improved and, in some cases, even IQ got a boost.205 So if you’re ADHD, and using Ritalin or Adderall and looking for a natural alternative, you may want to try DMAE. DMAE use in Cosmetics Most of the research on DMAE in the 1950’s and 60’s centered around using this compound for cognitive function and brain health. The most recent research on DMAE is primarily for using the compound in skin cosmetic formulas. DMAE has been shown to increase skin firmness even in young skin. One study with 30 healthy adults aged 36 – 49 applied DMAE gel or a placebo. The results of the study showed that DMAE-treated skin was much firmer.206 Another randomized clinical study used 3% DMAE facial gel applied daily for 16 weeks. The gel was able to reduce forehead lines, wrinkles around the eyes and improving lip shape and fullness. And the effects did not regress even 2-weeks after stopping application. Another open-label extension of the same trial showed that long-term application of DMAE gel had a good safety profile.207 Dosage Notes Recommended dosage of DMAE is 100 - 200 mg per day. DMAE nootropic supplements are usually sold as DMAE bitartrate. A capsule of DMAE bitartrate is only 37% DMAE and the rest is 67% tartaric acid. A 250 mg capsule of DMAE bitartrate yields 92.5 mg of actual DMAE. Take your DMAE dose in the morning before or with breakfast. Dose DMAE a few times a week, but not every day. If you are going to use DMAE, stack it with a good source of choline. Remember that DMAE inhibits choline and metabolism of choline. And you absolutely need choline and acetylcholine for a fully optimized brain. DMAE inhibits phospholipid synthesis. This means you won’t get much help with choline precursors. You need a good source of choline. Without getting into a long explanation of the mechanics – Phosphatidylcholine (PC) or CDP-Choline and Omega-3’s (DHA) can help offset the damage caused by long-term DMAE use.

Side Effects DMAE is considered non-toxic and safe for short-term or intermittent use. Your body naturally produces some DMAE on its own. You shouldn’t experience any side effects as long as you use DMAE in recommended doses. Some neurohackers report insomnia, headaches and muscle tension. Usually because the dose was too high. If you have a negative reaction to DMAE stop using DMAE. If you are planning on becoming pregnant do not use DMAE. Clinical studies have shown that DMAE may stunt the growth of the child’s brain.208 If you have epilepsy or bipolar disorder, you should avoid using DMAE entirely. See “Dosage Notes” about how to stack DMAE if you’re going to supplement with this nootropic. Available Forms DMAE is available in tablet, capsule, powder, liquid and creams. DMAE tablets and capsules are usually DMAE bitartrate (see “Dosage Notes”) and 150 – 350 mg. Depending on the size of capsule or tablet, do the conversion for pure DMAE, and start slowly with a low dose of 50 mg. And see how you respond. Nootropics Expert® Recommendation DMAE 100 – 200 mg per day I do NOT recommend using DMAE as a nootropic supplement. But if you must use DMAE, refer to the “Dosage Notes” and “Side Effects” in this chapter. Your body does make some DMAE on its own. But DMAE production inevitably declines with age. Some neurohackers report that using DMAE has a significant effect on concentration, memory, alertness, focus and mental clarity. But here at Nootropics Expert, I feel there are much more effective and safe ways to improve alertness, concentration, focus, and memory. If you’re going to use DMAE, start with 50 mg of DMAE per day. And see how you feel. Increase the dose no more than 50 mg at a time. And watch for side effects. Don’t forget to cycle it. Take it for a few days and take a couple of days off.

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5-HTP 5-HTP is known for relieving depression and anxiety, fibromyalgia, insomnia, migraines, obesity, and symptoms of Parkinson’s Disease 5-HTP (5-Hydroxytryptophan or oxitriptan) is an amino acid that is naturally produced in your body. 5-HTP is synthesized from the amino acid tryptophan which we get from food. 5-HTP is the immediate precursor of serotonin. And as a nootropic and dietary supplement, 5-HTP is popular with those who advocate its effectiveness in treating depression. Along with a number of other serotonin-related diseases. But using 5-HTP for treating depression and anxiety is not supported by science. The research is contrary to how 5-HTP is viewed by many, including medical doctors. When we dig into the research, we find that 5-HTP may be contraindicated for depression in those whom marketers advocate its use.209 I’m all for boosting neurotransmitter levels and optimizing cognitive performance here at Nootropics Expert. But now and again I run into a nootropic or dietary supplement that may be popular. But also may be a particularly bad idea. We’re going to get to the bottom of how 5-HTP works in your brain in this chapter. We’ll examine why it’s critical for brain health. And reasons why you may want to find another way to boost serotonin levels in your brain. So again, 5-HTP is an amino acid that’s synthesized from the essential amino acid tryptophan. Tryptophan is hydroxylated by tryptophan hydroxylase to 5-HTP (5-hydroxytryptophan), then decarboxylated to serotonin (5-hydroxytryptamine or 5-HT).210 Tryptophan → 5-HTP → serotonin 80-90% of your body’s serotonin is made in your intestines. But serotonin cannot cross the blood-brain barrier. So all the serotonin that your brain needs has to be made within the brain. This is where 5-HTP comes in… 5-HTP crosses the blood-brain barrier more readily than tryptophan. And gets synthesized into serotonin at a faster rate than from tryptophan.211 As a neurotransmitter, serotonin influences directly and indirectly, the majority of brain cells. So if you want to boost serotonin in your brain, some find that supplementing with 5-HTP is better than taking tryptophan. Tryptophan, which your body uses to make 5-HTP, can be found in turkey, chicken, milk, potatoes, pumpkin, sunflower seeds, turnip and collard greens, and seaweed. 5-HTP as a nootropic supplement is a naturally occurring amino acid derived from seed pods of

Griffonia simplicifolia, found in West and Central Africa. 5-HTP content in extracts of this plant vary from 2 – 20.83% (from seeds obtained in Ghana).212 How does 5-HTP Work in the Brain? 5-HTP is a precursor to serotonin. The neurotransmitter serotonin plays a role in sleep, appetite, memory, learning, mood, and sexual function. When tryptophan’s role in converting to 5-HTP for boosting serotonin doesn’t work efficiently, the result is often depression, chronic headache and insomnia. An open-label trial was conducted in Italy to determine the efficacy of using 5-HTP in young subjects with high levels of “romantic stress”. Serotonin has been linked to human romantic attachment. So researchers in this study set out to determine brain levels of Brain-Derived Neurotrophic Factor (BDNF) and serotonin in relation to changes in romantic stress (during the study). 15 healthy subjects (mean age 23.3 years) who had a “romantic breakup” took part. Participants received 60 mg of Griffonia simplicifolia extract containing 12.8 mg 5-HTP daily for 6 weeks. The subjects were evaluated for BDNF and serotonin levels at the beginning of the study, at 3 weeks and then again at the end of the 6-week trial. The scientists observed significant improvements in romantic stress scores from weeks 0 through 3. So far, 5-HTP seems to be working. But no further improvement was seen from weeks 3 through 6. Even though the young people had significantly higher levels of BDNF and serotonin.213 More Involved in Depression and Stress than Serotonin This “romantic breakup” study is a classic illustration of why using 5-HTP alone to treat depression and stress may not work. And if it does work, why it may not work for long. Depression is often more than simple serotonin dysfunction. Depression can also be associated with catecholamine dysfunction, including dopamine and/or norepinephrine. Or a combination of serotonin and catecholamine dysfunction. When you take 5-HTP alone, you are also depleting dopamine, norepinephrine, and epinephrine. Synthesis of serotonin from 5-HTP, and dopamine from L-DOPA is catalyzed by the same enzyme, Laromatic amino acid decarboxylase (AAAD). Dopamine and serotonin precursor supplementation must be taken in proper balance. Because when you use only 5-HTP, it dominates dopamine at the AAAD enzyme synthesis level. Blocking dopamine synthesis at the AAAD enzyme through competitive inhibition will lead to depletion of dopamine and the rest of the catecholamines.214 Going back to our Italian study of young people dealing with “romantic stress”, the subjects stopped responding to 5-HTP in the 2nd half of the study. Likely because their catecholamines became depleted

through continuous 5-HTP supplementation. Studies have found that when dopamine is depleted enough, 5-HTP will no longer function.215 Catecholamine Dysfunction Affects More Than Just Depression When catecholamine neurotransmitter levels (dopamine and/or norepinephrine) influence depression, supplementing with 5-HTP alone is not the way to go. Because you may deplete dopamine and norepinephrine, worsening the disease and its underlying cause. But this contraindication is not exclusive to depression. It extends to all other diseases where catecholamine dysfunction has been implicated. Including ADHD216, obesity, anxiety, seasonal affective disorder and Parkinson’s Disease.217 How things go bad Amino acid precursors of serotonin (i.e. 5-HTP) and dopamine (i.e. L-Tyrosine) work together during synthesis, metabolism, and transport to the point that they function as one system. When serotonin and dopamine are properly balanced, functions that are regulated only by serotonin, can be regulated by manipulating dopamine levels. And functions regulated only by dopamine in this balanced state can be regulated by manipulating serotonin.218 When you mess with this balance and improperly supplement with serotonin or dopamine precursors, you don’t get the desired effect of using that nootropic. And you increase the possibility of side effects. If you supplement with only one precursor (i.e. 5-HTP to boost serotonin) that dominates the other system (i.e. dopamine synthesis), depletion of the dominated system will occur (i.e. depleted dopamine). And if this effect is pronounced enough, you will not get the benefit you were aiming for when supplementing with the original precursor (i.e. 5-HTP). A powerful example of this effect is in the management of Parkinson’s Disease where the effects of LDOPA are no longer observed over time due to serotonin depletion.219 Since serotonin and dopamine cannot cross the blood-brain barrier, the number of serotonin and dopamine molecules in the brain is a function of the amount of nutrients (amino acid precursors) that are available to be synthesized into new neurotransmitter molecules. Optimizing brain function with minimal side effects is NOT a function of supplementing until you get sufficiently high amino acid levels. It’s a function of achieving the proper balance between serotonin and dopamine. 5-HTP benefits 5-HTP is absolutely critical for synthesis of serotonin in your brain. But supplementing with 5-HTP to boost serotonin does not work well. Using 5-HTP to treat depression has had very little success over the last few decades of clinical trials

and biohacking. Integrating 5-HTP into your nootropic stack is much more complicated than simply adding some 5-HTP in order to boost serotonin. 5-HTP alone will not work for depression, or any other issue you’re dealing with involving the catecholamines (dopamine, norepinephrine, epinephrine) because of 5-HTP’s tendency to deplete those neurotransmitters. 5-HTP will boost serotonin in your brain.220 But 5-HTP must be carefully stacked with precursors for dopamine and norepinephrine or you risk making the situation worse. You must avoid supplementing with only one of the serotonin or dopamine amino acid precursors. When amino acid precursors are not in balance, you end up with decreased effectiveness of that nootropic, increased side effects, and depletion of the nondominant system. How does 5-HTP feel? Reactions to supplementing with 5-HTP vary considerably. But the one consistent theme is initial feelings of well-being, better sleep, less need for sleep, improved mood, less social anxiety, lower appetite, improved tolerance for stress and improved cognitive function. And after a couple of weeks of dosing 5-HTP - side effects begin. Serotonin overload results in dopamine and norepinephrine depletion. Side effects include feelings of lethargy, depression, brain fog, stomach pain, and headaches. Worst case scenario is nausea, vomiting and even blacking out. Neurohackers who report consistent success supplementing with 5-HTP stack it with B-Vitamins, a dopamine precursor like NALT, and only use 5-HTP as needed. Those who have a bad experience with 5-HTP from the start often have no idea why they’ve reacted badly. But an educated guess is their depression was catecholamine (dopamine, norepinephrine, epinephrine)-related. And boosting serotonin made their dopamine-related issues worse. Very quickly. One huge word of WARNING: Do NOT take 5-HTP with any antidepressant medication. You put yourself in the very real danger of Serotonin Syndrome which can ultimately kill you. The Research 5-HTP supplements are heavily marketed as a natural remedy for depression. But the science does not support using 5-HTP for depression. We have decades of clinical trials available. And there is no evidence of the efficacy in using 5-HTP for depression. The Department of Public Health at the University of Queensland Medical School in Australia did a systematic review of literature dating from 1966 – 2000 for “5-HTP” and “depression”. The researchers found 108 clinical studies of which only 2 studies, one with serotonin (5-HT) and one

with L-Tryptophan for a total of 64 patients met sufficient quality criteria to be included. These studies suggest serotonin (5-HT) and L-Tryptophan are better than placebo at alleviating depression. But the researchers noted “the small size of the studies, and the large number of inadmissible, poorly executed studies, cast doubt on the results from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness.”221 5-HTP for Fibromyalgia A double-blind, placebo-controlled trial in Italy studied the efficacy of using 5-HTP in treating fibromyalgia symptoms. 50 patients with primary fibromyalgia syndrome were selected for this study. This 1990 study did not publish the amount of 5-HTP used. But the researchers found a significant improvement in fibromyalgia symptoms with only mild and transient side effects.222 5-HTP for the Treatment of Depression Insufficient activity of the neurotransmitters serotonin and norepinephrine is a central element of the model of depression most widely held by neurobiologists today. In the late 1970’s and 1980’s, numerous studies were performed in which depressed patients were treated with the serotonin precursors L-Tryptophan and 5-Hydroxytryptophan (5-HTP), and the dopamine and norepinephrine precursors Tyrosine and L-Phenylalanine. A summary published in the Alternative Medicine Revue looked at the data from all these studies. The author noted that the nature of the studies makes it difficult to draw firm conclusions regarding the efficacy of neurotransmitter precursors for treating depression. While there is evidence that precursor loading could work, particularly for serotonin precursor 5-HTP, more studies of suitable design and size “might lead to more conclusive results”.223 Those studies have not materialized since that report was published 16 years ago. Dosage Notes Recommended dosage of 5-HTP if you’re going to try it, is 50 mg 1 – 3 times per day. Some studies have used higher doses than my recommended dose, but 5-HTP can be toxic at high doses. For anxiety or depression, 5-HTP is dosed at 150 – 300 mg per day total. To relieve post MDMA (Ecstasy) depression, 5-HTP 100 mg on Day 3-7 after MDMA use.224 Successfully supplementing with 5-HTP requires stacking it with a dopamine precursor like L-Tyrosine or L-DOPA along with B-Vitamins (for synthesis), and one of the sulfur-containing amino acids (methionine, cysteine, homocysteine, or taurine). And you must monitor the effects this stack is having on your body. If you start experiencing side

effects of any kind, it’s a good indication that either serotonin or dopamine is out of balance. DO NOT combine 5-HTP with any kind of antidepressant medication. Combining SSRI’s, Tricyclics or MAOI’s with 5-HTP will cause Serotonin Syndrome. An extremely dangerous condition involving severe mental changes, hot flashes, rapidly fluctuating blood pressure and heart rate, and possibly coma. Serotonin Syndrome can kill you. And I’m not kidding here. Side Effects 5-HTP supplementation can cause heartburn, heart palpitations, headache, stomach pain, nausea, vomiting, diarrhea, drowsiness, sexual problems, and muscle issues. 5-HTP can also cause some pretty radical mood changes including agitation, aggressiveness, anxiety, euphoria, poor decision-making, irritability, psychosis, restlessness and insomnia. 5-HTP can make the symptoms of schizophrenia, bipolar disorder, and other mental disorders worse. And I can’t emphasize this enough so I’m going to repeat it here in case you missed it… DO NOT combine 5-HTP with any kind of antidepressant medication. Combining SSRI’s, Tricyclics or MAOI’s with 5-HTP will cause Serotonin Syndrome. An extremely dangerous condition involving severe mental changes, hot flashes, rapidly fluctuating blood pressure and heart rate, and possibly coma. Serotonin Syndrome can kill you. And I’m not kidding. Available Forms 5-HTP is made from tryptophan in your body. 5-HTP as a nootropic supplement is made from extracts of the African tree Griffonia simplicifolia. 5HTP supplements are typically in tablet or capsule form. You’ll often find 5-HTP in many ready-made vitamin and herbal formulas. Nootropics Expert® Recommendation 5-HTP 50 mg up to 3-times per day I DO NOT recommend using 5-HTP as a nootropic supplement. Your body does synthesize 5-HTP on its own to make serotonin in your brain. You can’t get 5-HTP from food. But you can get L-Tryptophan from food which is synthesized into 5-HTP in your body. 5-HTP may help you if you’re dealing with depression. But you must stack it with a dopamine amino acid precursor, along with B-Vitamins, and a sulfur-containing amino acid. See the “Dosage Notes” in this chapter.

IF you are going to try 5-HTP, I suggest starting with a dose of 50 mg daily. You may want to take it in the evening because it could help you sleep. Short-term dosing of 5-HTP of no more than 2 weeks seems to provide the most benefit if you’re going to benefit from this nootropic. Or try using 5-HTP only on an “as needed” basis. For a mood boost, improve social anxiety, and provide a short-term boost in cognition. Unless you are using 5-HTP to alleviate the symptoms after using Extasy (MDMA), 5-HTP supplementation on its own is NOT recommended. Nor is it recommended for long-term use.

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Fisetin Fisetin is anti-aging, has been shown to boost learning and memory, improve mood, reduce back & arthritic pain, reduce inflammation, improve cognition in Alzheimer’s, and reduce allergies Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a flavanol found in fruits and vegetables such as strawberries, apples, persimmons, grapes, onions, and cucumbers.225 The highest concentration of Fisetin is found in strawberries followed by apple and persimmon. Recent anti-aging research has shown Fisetin to be the most potent senolytic compound compared to all other flavonoids. Senolytic means destroying dysfunctional cells that refuse to die.226 Fisetin has been found to be anti-tumor, antioxidant, neurotrophic and anti-inflammatory. Fisetin also helps your body and brain to produce glutathione which is your master antioxidant.227, 228 Fisetin is currently being studied for boosting memory performance and Alzheimer’s. Fisetin has been shown to increase long-term potentiation needed for encoding long-term memory.229 Studies have demonstrated Fisetin to be the most effective flavonoid to promote dendrite outgrowth. Dendrites are the equivalent to ‘receiving antenna” on neurons and used in brain cell signaling.230 Fisetin protects neurons from damage due to oxidative stress. It boosts glutathione which is your main antioxidant protecting against inflammation. And it suppresses gene expression of tumor-necrosis factor – alpha (TNF-α), interleukin (IL)-1β, COX2, and inducible nitric oxide synthase which provides potent anti-inflammatory activity in brain microglia.231 How does Fisetin work in the brain? Fisetin boosts brain health and function in several ways. But two in particular stand out. 1. Fisetin is Anti-Aging. The most promising research and what has gained the most attention is Fisetin and its potential ability to extend lifespan. Senescent cells are cells that have become dysfunctional and are not eliminated from your system as you age. They just hang around in your body and release toxins that damage nearby healthy cells.232, 233 The accumulation of senescent cells causes inflammation which results in age-related diseases such as osteoporosis, cancer, heart disease and cognitive dysfunction. An animal study published in 2018 showed Fisetin effectively removes senescent cells. In aging mice, Fisetin helped increase their lifespan by 10 percent.234, 235 The Mayo Clinic are currently conducting a clinical trial with older postmenopausal women to determine if Fisetin is as effective at removing senescent cells in aging humans. And potentially

extending lifespan.236 2. Fisetin may help prevent Alzheimer’s. As you age, learning and memory decline partly because of increases in oxidative stress, inflammation, cerebral blood flow decline, β-amyloid accumulation, and tau tangles. A study conducted at the Salk Institute using animal models of Alzheimer’s disease and dementia found that Fisetin helped reduce cognitive deficit in aging mice while restoring markers associated with impaired synaptic function, stress, and inflammation.237 Another study showed that Fisetin helped reduce Alzheimer’s symptoms by reducing the accumulation of β-amyloid proteins and reversed synaptic dysfunction resulting in improved learning and memory.238 How things go bad As you get older, the chemistry in your brain and energy metabolism changes. ↓ Neurons and synapses degenerate ↓ Recall, reaction time, memory, and mood diminish ↓ Cerebral circulation decreases ↓ Learning and memory decline ↑ Increased free radicals damage cells ↑ Inflammatory and oxidative stress damages brain cells Age-related changes contributing to the neurodegenerative diseases of aging including Alzheimer’s, Parkinson’s, and dementia. But even if things have not degenerated to such a debilitating level, Fisetin can help. Fisetin Benefits Fisetin is a polyphenol which are among the most effective natural ways to combat aging. And to prevent the health issues that often lead to cardiovascular and neurodegenerative diseases. Fisetin has the unique ability to increase cell apoptosis. And promotes cell death which gives way for healthy new cells to thrive. Studies conducted using Fisetin show increased brain antioxidant levels, which helps prevent microglia from releasing inflammatory compounds.239, 240 Fisetin has been shown in animal studies to help prevent cancer by reducing the formation of new blood vessels in various forms of cancer and starves tumor cells of oxygen and glucose.241 In other animal studies Fisetin was shown to improve memory, reduce inflammation, and prevent the loss of brain cell function. Fisetin has been shown to reduce β-amyloid plaque buildup and prevent the

loss of healthy brain cells.242 And Fisetin helps your body produce Glutathione which is your master antioxidant supporting healthy immune function.243 How does Fisetin feel? Neurohackers who supplement with Fisetin report better focus, memory, and mood. Some say they are more alert even when they haven’t had sufficient sleep the night before. Several Fisetin users report less back pain and less arthritic pain. Some Fisetin users report an increase in mental clarity and overall sense of well-being. And some say Fisetin helped reduce their allergies. Fisetin Clinical Research Note that nearly all clinical studies conducted with Fisetin so far have been animal studies or with cells in a petri dish. Fisetin for depression Anyone who suffers from depression knows the negative effects on quality of life. Recent animal studies demonstrated the anti-depressant effects of supplementing with Fisetin. In this study, Fisetin provided its antidepressant effects by modulation of the serotonin pathway by inhibition of monoamine oxidase-A. Fisetin also modulates norepinephrine which may also contribute to its anti-depressive effects.244 Fisetin for memory and cognition When aging rats were given Fisetin, they experienced an improvement in learning and memory. Studies revealed that Fisetin activates pathways in the brain involved in encoding and storing memories. The study also showed that Fisetin prevented memory loss in mice exposed to toxins.245, 246 Fisetin for neurodegenerative disease In one study, Fisetin improved brain antioxidant levels and prevented microglia from releasing inflammatory compounds in response to bacterial toxins.247, 248 In mice with β-amyloid plaque accumulation, Fisetin improved memory, reduced inflammation, and prevented the loss of brain cell function. In mice with Alzheimer’s, it reduced β-amyloid plaque buildup and loss of brain cells.249 Fisetin protects against stroke Fisetin protects brain cells and reduces inflammation and damage due to stroke in mice and rats.250, 251, 252

In a 2008 study conducted with rabbits, Fisetin prevented loss of balance, lack of energy, and uncontrolled eye movements caused by stroke.253 Fisetin does this by reducing inflammation and brain damage after a stroke. Another study was conducted with mice suffering from inflammation and oxidative stress caused by aluminum. Aluminum toxicity has been linked to Alzheimer’s disease. Fisetin reduced inflammation and oxidative stress in the brain caused by aluminum.254, 255 Fisetin supports the survival of brain cells by eliminating damaged or unneeded proteins.256 Fisetin Recommended Dosage Since all clinical studies with Fisetin were conducted with animals and not humans there is no established recommended dosage. Most Fisetin supplements range from 100-500 mg. In clinical trials, the equivalent human daily dose of 100-1400 mg of Fisetin were used. Fisetin easily crosses the blood-brain barrier and appears to promote cell communication in the hippocampus. A part of your brain associated with long-term memory.257 Fisetin is fat-soluble and must be taken with a healthy fat like unrefined coconut oil to ensure absorption. Fisetin Side Effects Fisetin is non-toxic and is well-tolerated by most people. We do not have any human studies on Fisetin and must rely on user reviews. And because we do not have any human studies to verify its safety, you may want to avoid using Fisetin if you are pregnant or breastfeeding. Type of Fisetin to Buy Fisetin supplements are available in tablets, softgels, and capsules. Capsules are typically 100-500 mg each. Fisetin is a natural bioflavonoid and polyphenol similar to Luteolin and Quercetin. You naturally get very small amounts of Fisetin by eating strawberries, apples, persimmons, grapes, onions, and cucumbers with the highest concentration found in strawberries. The Salk Institute for Biological Studies have been researching Fisetin for years and own a patent for Fisetin as a memory enhancer.258 Fisetin is poorly absorbed by your digestive system so dietary supplement companies offer various unique solutions for enhancing absorption. Novusetin® – by Bioriginal Food & Science Corp. located in Saskatoon, Canada – is a patented form of

Fisetin sourced from the Japanese fruit wax tree and licensed to supplement companies Liposomal Fisetin is another attempt to improve absorption by encasing the Fisetin molecule in a phospholipid. And is often combined with another polyphenol Quercetin which is also thought to boost absorption. Fisetin is fat-soluble, so consuming it with a healthy fat promotes better absorption no matter what the supplement label states. Nootropics Expert® Recommendation Fisetin 100-500 mg a day I recommend supplementing with Fisetin as a nootropic supplement. Your body does not make Fisetin on its own. So, to get its benefits you must take it as a supplement. Or rely on the tiny amount you get from strawberries. Fisetin is especially helpful for those suffering from allergies, arthritic pain, muscle soreness after a workout, or a cold. Fisetin is gaining a reputation as an anti-aging supplement because it helps remove senescent cells which are dysfunctional cells that if left unchecked cause inflammation, oxidative stress, and eventually neurodegenerative disease such as Alzheimer’s. Fisetin is reported by aging neurohackers as helping with long-term memory. Fisetin also shows promise in animal studies for helping reduce some of the symptoms associated with Alzheimer’s. So, if you or a loved one are dealing with Alzheimer’s I highly recommend trying Fisetin and see if it helps. Fisetin is fat-soluble so must be taken with a healthy fat like unrefined coconut oil to ensure absorption. Fisetin is also not very bioavailable so consider trying Liposomal Fisetin or a supplement containing the patented form called Novusetin®. Fisetin as a nootropic seems to be effective starting at 100 mg up to 500 mg per day. Dosages above 1,000 mg per day are used by some. But remember all we have are animal studies to rely on and do not have any information regarding the safety of long-term use.

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Forskolin Forskolin has been shown to boost memory and learning, improve motivation and mood, and stimulate cerebral circulation Forskolin (Coleus forskohlii) is the only known nootropic supplement to naturally boost cAMP (Cyclic Adenosine Monophosphate) in your brain.259 cAMP is important for neural signaling within brain cells. As a secondary messenger in neurons, cAMP produces proteins needed for neuron and synapse growth. This process is called Long-Term Potentiation (LTP). LTP is the process where synaptic connections get stronger in response to electrical stimulation in the brain. This process happens naturally through life experience. It’s a critical part of synaptic plasticity. And how experience is recorded through learning and memory. Forskolin is a chemical compound extracted from Coleus forskohlii (Plectranthus barbatus), a perennial plant native to India, Burma and Thailand. Forskohlii has been used for millennia in traditional Ayurvedic medicine to treat heart disease, convulsions, spasms, and painful urination.260 Forskolin is used in Western homeopathic medicine to treat allergies, skin conditions, obesity, PMS, irritable bower syndrome, urinary tract infections, bladder infections, cancer, blood clots, male infertility, insomnia and convulsions. Some healthcare providers even use Forskolin intravenously (IV) for heart failure. Researchers and holistic medical practitioners use the extract Forskolin to boost cerebral blood flow, lower blood pressure, treat hypertension, asthma, and congestive heart failure. But here, we’re looking at Forskolin as a nootropic. Recall that Forskolin boosts cAMP. cAMP was discovered in 1956 and its production is now known to be the final common pathway for many hormones and transmitter agents. To put this in practical perspective, hormones and neurotransmitters do not enter the cell. Instead, they activate a receptor on the cell membrane that is part of the adenylate cyclase enzyme complex. The production of cAMP in a cell is catalyzed by this complex. The cyclic AMP (cAMP) then activates cAMP dependent protein kinase (PKA), which results in changes in the cell’s function.261 Based on input from the relevant hormone or neurotransmitter. The elevation of cAMP along with PKA is required for long-term potentiation (LTP). This increase in neuroplasticity is how long-term memories are formed and encoded in your brain. Researchers have found that increases in cAMP rapidly activates the Brain-Derived Neurotrophic Factor (BDNF) receptor TrkB and induces BDNF-dependent long-term potentiation at the Schaffer collateral-CA1 synapse in the hippocampus.262

In simpler terms, Forskolin boosts cAMP levels which affects long-term potentiation (LTP). LTP is an integral part of the process in developing and encoding long-term memories. How does Forskolin work in the Brain? Forskolin boosts brain health and function in several ways. But two in particular stand out. 1. Forskolin enhances memory. Forskolin as a nootropic has the unique ability to activate the enzyme adenylate cyclase (AC). The activated AC enzyme then converts to cAMP (Cyclic Adenosine Monophosphate), a secondary messenger used for intracellular communication.263 cAMP helps stimulate the production of CREB (cAMP response element-binding protein). An increase in CREB enhances Long-Term Potentiation (LTP). LTP is the connection between brain synapses. Strengthening in response to stimulation by neurons on either side. A major component in both learning and memory. Memories are stored at a cellular level. And retrieved at a cellular level. This well-travelled pathway is strengthened by boosting cAMP with Forskolin.264 2. Forskolin increases cerebral circulation. Coleus forskohlii has traditionally been used to treat hypertension (high blood pressure), congestive heart failure and angina (reduced blood flow to the heart). Forskolin is very effective in lowering blood pressure. And scientists believe this ability to boost blood flow is related to Forskolin’s cAMP-elevating ability. Researchers recruited 7 patients with dilated cardiomyopathy (DCM). DCM is a condition in which the heart’s ability to pump blood is decreased due to the left heart ventricle being enlarged and weakened. Forskolin administration dramatically improved left ventricle function. And increased overall cardiovascular performance.265 Another group of scientists set out to study the effects of Forskolin on cerebral circulation. In this study, rabbits were anesthetized and measuring devices were attached to blood vessels entering and coming out of the brain. The study found that Forskolin was an effective cerebral vasodilator. Enlarging blood vessels in the brain boosted blood flow. Allowing for more efficient delivery of nutrients and oxygen to brain cells.266 How things go bad Environmental factors like the food we eat, exposure to toxins, polluted air, ADHD, illness, stress and aging changes our brain chemistry. ↓ Mood and motivation declines ↓ Memory and recall decline ↓ Long-term memory fades

All of these changes are contributing factors to poor quality of life. And as they progress, to neurodegenerative diseases like Alzheimer’s, dementia and Parkinson’s. Forskolin benefits Research from hundreds of studies, and feedback from neurohackers have shown that Forskolin can: • • •

Improve memory by boosting cAMP activity in the brain Boost catecholamines (dopamine, norepinephrine, and epinephrine) in the brain Boost cerebral circulation

Forskolin is fat-soluble and quickly enters your brain after you take it. Once in your brain, it boosts cAMP activity. cAMP is involved in the Long-Term Potentiation process of preserving memories. Forskolin combined with Artichoke extract is even more effective. Forskolin effectively boosts cAMP levels but also increases PDE4 in the brain. PDE4 is a cAMP inhibitor and will counteract increases by Forskolin if left unchecked. Inhibiting PDE4 with Artichoke Extract and boosting cAMP with Forskolin also potentiates dopamine release in the brain. Boosting processes in this stream of chemical reactions in the brain increases learning and memory.267 Without the side effects of stimulating dopamine production through the use of drugs like Adderall or Ritalin. How does Forskolin feel? Many neurohackers report that Forskolin with Artichoke Extract improves mood. It motivates you to want to learn, and to get things done. Some say it works as good as Modafinil. The general consensus is: • • • •

Improved long-term memory Increased ability to retain information Increased ability to study Improved mood and motivation

The Research Forskolin as a nootropic cAMP responsive element binding protein (CREB) is a protein that modulates the transcription of genes. Increases in cAMP triggers the activation of CREB. And this transcription factor is a big part of intracellular signaling. It regulates everything from the production of new sperm cells in men (spermatogenesis), to the circadian rhythms that control your sleep and awake cycles, to memory formation. Forskolin increases cAMP which triggers the activation of CREB. Researchers have found through animal studies that CREB is required for a variety of complex forms of memory, including spatial memory and social learning.268

Forskolin reduces anxiety Benzodiazepines (Benzos) like Valium are a class of psychoactive drug used to treat anxiety, insomnia, agitation, muscle spasms, alcohol withdrawal and before medical and dental procedures to keep the patient calm. Benzodiazepines come with a whole host of negative side effects including addiction, cognitive impairment, decreasing effectiveness (tolerance) and nasty withdrawal symptoms. Scientists have been studying non-GABAergic substances that elevate cAMP, and have anti-anxiety activity. So they took a look at Forskolin. In one animal study, researchers compared the effects on anxiety of Forskolin compared to diazepam (Valium). And found that Forskolin produced significant anti-anxiety activity in both stressed and unstressed animals. Diazepam had an anti-anxiety effect on the unstressed animals. But did not work for stressed animals. The researchers noted that the anti-anxiety activity of Forskolin was accompanied by a significant elevation of cAMP levels. There’s cAMP again… The researchers concluded that Forskolin was a better option for treating anxiety. This non-receptor mediated anti-anxiety action through cAMP elevation was preferable to the adverse reactions people get from using receptor-mediated drugs like Benzos.269 Forskolin as a neuroprotectant in chemical warfare If you ever find yourself in a warzone, you may want to have a bottle of Forskolin with you. Acetylcholinesterase (AChE) is the primary cholinesterase in your body. This enzyme catalyzes the breakdown of acetylcholine (ACh) once ACh is used in the synaptic cleft during neurotransmission. This is how it works… During neurotransmission, ACh is released from the first neuron into the synaptic cleft of the 2nd neuron where it binds to ACh receptors. And does its job of passing on the neural signal. Once ACh has done its job, AChE which is also located in that synaptic cleft, steps in and breaks down acetylcholine (ACh) by liberating the choline. The liberated choline is taken up again by another neuron, and ACh is synthesized by combining the free recycled choline with Acetyl-CoA through the action of choline acetyltransferase. Chemical warfare agents like Sarin gas, and insecticides like malathion, act to inhibit AChE. Which means they shut down this recycling process needed for acetylcholine production in the brain. Researchers have demonstrated that Forskolin is a very effective AChE promoter. Forskolin activates AChE and up-regulates its expression. Using mouse models, the scientists showed that Forskolin boosted AChE expression outside and inside the affected brain cells. They concluded that Forskolin can sufficiently upregulate cellular AChE production and protect cells

against chemical warfare agents like Sarin.270 Forskolin works to protect your brain from damage caused by insecticides too. So if your using an insecticide in the house or out in your garden, you may want to protect your brain by dosing with Forskolin first. Dosage Notes Recommended dosage for Forskolin is 250 mg of Coleus forskohlii at 10%, or 125 mg of Coleus forskohlii at 25%. For boosting cAMP in a CILTEP stack: 4 mg Forskolin extract per day along with 900 mg of Artichoke Extract for PDE4 suppression. NOTE: You will not get the full nootropic benefit of using Forskolin if you dose it on its own. Forskolin tends to boost cAMP and PDE4 levels. And PDE4 suppresses cAMP. Artichoke Extract helps control PDE4. And don’t worry about measuring out an accurate 4 mg for this CILTEP stack. I’ve been using 250 mg of Forskolin (10% ForsLean®) with 900 mg of Artichoke Extract (6%) with great success. For counteracting Forskolin’s effect on Acetylcholinesterase: 800 mg Acetyl-L-Carnitine (ALCAR) – (200 mg of ALCAR for every 1 mg of Forskolin) per day. Many users of this stack report it helpful to supplement with 500 mg Phenylalanine, a B-Vitamin Complex and caffeine (coffee or preferably green tea). Side Effects Forskolin induces CYP3A gene expression in your liver. Which means, like grapefruit juice, Forskolin needs to be used cautiously as it will amplify the effects of other nootropics in your stack. And prescription meds.271 Acetylcholinesterase is upregulated by cAMP which makes you sleepy. This means that available Acetylcholine (ACh) in your brain drops. You can counteract this with Acetyl-l-Carnitine (ALCAR), which calms the upregulation of Acetylcholinesterase. The most common side effect with Forskolin is diarrhea because increased cAMP affects the smooth muscle in your gastrointestinal tract. Things move through your intestines faster with Forskolin. But this side effect usually happens at much higher than recommended doses of Forskolin. Forskolin reduces blood pressure. So if you’re on high blood pressure meds or have naturally low blood pressure you should avoid using Forskolin. Available Forms Forskolin is usually marked as “Forskolin” or “Coleus forskohlii” on the bottle. Forskolin typically comes in 125 mg capsules of Coleus Forskohlii (25% Forskolin), or 250 mg

capsules of Coleus Forskohlii (10% Forskolin). Look for a Coleus forskohlii or Forskolin supplement with the percentage of Forskolin extract clearly marked on the label. ForsLean® by Sabinsa Corporation is a branded and patented form of Coleus forskohlii that’s been used most often in human trials. So we prefer a supplement that uses ForsLean® as their source of Forskolin. Researchers in India reported that Forskolin concentration can change significantly depending on where the Coleus forskohlii is grown.272 And why we prefer a standardized version like ForsLean®. Nootropics Expert® Recommendation Forskolin Extract 125 - 250 mg per day I recommend using Forskolin as a nootropic supplement. Your body does not make Forskolin on its own. So to get its benefits you must take it as a standardized supplement. Forskolin on its own as a supplement for cognition and memory is not very effective because it increases PDE4 (a cAMP reducer) along with boosting cAMP. So the nootropic effects cancel each other out. But Forskolin is especially helpful when combined with Artichoke Extract. It helps boost memory, increases motivation and the desire to learn. And helps improve mood while controlling anxiety. I suggest dosing Forskolin 125 – 250 mg per day with 900 mg of Artichoke Extract taken in the morning. Stack this with at least 800 mg of ALCAR to keep your acetylcholine levels up. I’ve also found that combining this stack with caffeine is helpful. The L-Theanine in green tea comes with the caffeine boost we need. Without the side effects of coffee. And finally, we are making the effects of normal dopamine function more effective with this stack. It triggers the desirable downstream processes that increase learning and memory. The chemical dynamics of the dopamine are preserved. And we don’t get the negative side effects of using a stimulant like Adderall or Ritalin. This Forskolin/Artichoke Extract stack increases mental endurance for encoding long-term memories.

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GABA GABA has a calming effect on brain and body, helps relieve stress and anxiety, and boosts Human Growth Hormone GABA (gamma-aminobutyric acid) is an amino acid and neurotransmitter. GABA is your brain’s primary inhibitory transmitter. Its role is to keep glutamate, the primary excitatory transmitter, from overwhelming you. GABA is synthesized in brain cells from glutamate. It’s estimated that 40% of the synapses in the human brain work with GABA and therefore have GABA receptors. GABA enhances normal sleep cycles and improves blood pressure. GABA stimulates the pituitary gland to secrete Human Growth Hormone. And helps produce endorphins that make you feel good after a workout or sex. Too much glutamate can cause a seizure, and too much GABA can put you in a coma. A healthy brain maintains a critical balance of GABA and glutamate. GABA acts like a “brake” on neuron circuits during stress. Low GABA levels can result in anxiety, insomnia, poor mood and restlessness. Clinical studies show that boosting GABA with a supplement relieves anxiety, stress, and boosts the production of alpha brain waves.273 If GABA is optimized in your brain, you’ll feel focused, relaxed and stress-free. When you normalize GABA levels you’ll experience a reduction in anxiety, insomnia, nervousness, restlessness and stress. Benzodiazepine drugs like Valium and Xanax work by increasing GABA receptor sensitivity.274 How does GABA Work in the Brain? GABA helps brain health and function in several ways. But two in particular stand out. 1. GABA works by preventing neural signaling associated with anxiety from reaching other neurons. It does this by attaching to the receptors that would otherwise excite those neurons. Overstimulating neurons in certain areas of your brain is what causes anxiety-related symptoms. Researchers in Japan studied the calming effects of GABA with 8 volunteers. They had study subjects cross a suspension bridge as the stressful stimulus. The placebo subjects in this group showed significant drops in blood level markers indicating high stress levels. While the GABA group showed significantly higher blood levels of these same markers. GABA worked as a natural relaxant and its effects could be seen within 1 hour of taking GABA. The researchers concluded that GABA could enhance immunity from stress.275

2. GABA also helps decrease Beta brain waves and increase Alpha brain waves.276 Beta brain waves are important for attention, alertness, concentration and developing memories. But excess levels of concentration, particularly during stress, can lead to anxiety, depression, insomnia and more stress. When you are in an alert state, both Alpha and Beta brain waves can be stimulated. But the type of alertness will determine which brain wave is produced. Alertness during an Alpha wave state is associated with a relaxed state. And a stressed alert state produces a Beta wave. But an excess of Beta brain waves contributes to a variety of nervous disorders including anxiety and stress. As a side note, I’m writing this while listening to binaural music which produces an Alpha state. It allows for a relaxed environment which promotes creativity and productivity. How things go bad Low levels of GABA are associated with a variety of health problems. ↑ Anxiety277, panic attacks, stress and insomnia ↑ Muscle spasms, hypertension, convulsion, Tourette’s Syndrome, and epilepsy ↑ Dry skin and wrinkles ↑ Poor digestion, bloating, flatulence, and constipation When your neurotransmitters, including GABA, are in balance, you feel motivated, productive, and energetic. And you feel calm and relaxed during downtime. When GABA levels are low you feel filled with dread, you’re constantly worried, you have racing thoughts, and you’re frequently late and disorganized.278 Many people in this GABA-slump resort to high carbohydrate foods, and drugs or alcohol to relax. GABA benefits The amino acid L-glutamine is the precursor to GABA production in your body. L-glutamine gets converted to glutamic acid or glutamate. Glutamate is your body’s most abundant excitatory neurotransmitter. Which is responsible for attention span, brain energy, learning ability, memory, and staying awake. An enzyme called glutamate decarboxylase converts glutamate to GABA. It does it with the help of the active form of Vitamin B6 (Pyridoxal-5-Phosphate (P5P)). The amino acid taurine helps increase the communication and productivity of this enzyme. And zinc helps the release of GABA from its receptors. When this process works efficiently, you feel relaxed with no stress or feelings of anxiety. And you get

a more restful night’s sleep. How does GABA feel? When you balance GABA levels in your brain, you feel relaxed and calm. But many neurohackers who try using GABA as a supplement don’t feel the effects. Because the GABA molecule is too large to cross the blood-brain barrier.279 If you do feel the calming effects of GABA within a ½ hour of taking it, it may mean you have a “leaky” blood-brain barrier. Not a good thing.280 Because if GABA can get through, all kinds of nasty stuff can get through too. Including toxins, undigested food particles and anything else in your blood stream that shouldn’t be in your brain. But the good news is, supplementary GABA can also benefit other functions in your body. GABA is found in your adrenal glands, pituitary gland, pancreas and your sex organs.281 GABA is also anti-inflammatory and has an immune benefit. When all these are running optimally, you’ll feel good. We’ll also cover other ways to boost GABA levels in our brain in the “Available Forms” section of this chapter. The Research GABA was identified as a neurotransmitter several decades ago. And there has been a lot of research on GABA published since. But most of it is focused on how GABA works. And the drugs and chemicals which affect its action. There is very little research available on using GABA as a supplement. Likely because most scientists believe that GABA taken as a supplement will not cross the blood-brain barrier. GABA Increases Human Growth Hormone Bodybuilders and athletes use supplementary GABA to help repair and build muscle. And there are several studies supporting the notion that GABA increases Human Growth Hormone. In one study, researchers worked with 19 subjects who were given a single oral dose of 5 grams of GABA. 18 subjects were given a placebo during this trial. 3 hours after the administration of GABA, blood samples were taken. The team reported that “GABA caused a significant elevation of plasma growth hormone levels”.282 GABA helps Reduce Insomnia A Los Angeles study conducted a randomized, double-blind, placebo controlled trial with 18 patients with sleep disorders. The patients received either a placebo, or Gabadone (a combination of GABA and 5-hydroxytryptophan). The difference between the two groups of sleep-deprived patients was significant. The Gabadone group fell asleep faster, stayed asleep longer, and had a better quality of sleep than the placebo group.283

Dosage Notes The recommended daily dosage of GABA is 500 to 1000 mg for a relaxation or calming effect. Some neurohackers notice an immediate relaxing effect, while others need to take it for a couple weeks before it starts to kick in. L-Arginine which increases nitric oxide also helps supplementary GABA cross the blood-brain barrier.284 PharmaGABA™ which is a natural form of GABA produced with the help of Lactobacillus hilgardii bacteria is dosed at 50 – 200 mg per day. Side Effects GABA is considered very safe when taken in normal recommended doses. Bodybuilders who use much higher doses of GABA do report experiencing flushing, tingling, a spike in heart rate and blood pressure, and anxiety. Available Forms GABA as a supplement is available in tablet, capsule and powder. Scientists have shown that GABA does not readily cross the blood-brain barrier. But many neurohackers report feeling a calming effect when using GABA. PharmaGABA™ is a natural form of GABA made using Lactobacillus hilgardii bacteria. The same bacteria used to ferment vegetables when making the Korean cabbage dish called kimchi. This form seems to readily cross the blood-brain barrier. Another safe way to change GABA action in the brain is to use any of following commonly used herbs, vitamins and minerals. Valerian root 285, American Ginseng and Kava Kava work by increasing the effect of GABA on its receptors. Extracts of green, black and oolong tea also elicit a GABA effect.286 Magnesium binds to GABA receptor sites and increases its effect.287 Taurine protects against glutamate overstimulation. And this inhibitory effect acts as an anxiolytic (anti-anxiety). The neurotransmitter Serotonin enhances GABA. So precursors to Serotonin like tryptophan and 5HTP can increase GABA action in the brain. The amino acid Theanine in tea provides a calming effect. Theanine inhibits glutamate uptake which would increase GABA levels in the brain.288 And Phenibut, which is a derivative of GABA developed in Russia, also increases levels of GABA in the brain. While some report that Phenibut causes drowsiness and fatigue, it’s a much safer way to boost GABA than with a pharmaceutical like Valium or Xanax. Nootropics Expert® Recommendation

GABA 500 – 1,000 mg per day. I recommend using GABA as a nootropic supplement if you’re feeling anxiety or stress. And to calm or keep in check some of the stimulatory effects of some nootropics. Your body does make GABA on its own from glutamate in your brain. Most healthy people have an adequate supply of GABA. But if you’re dealing with anxiety or stress and need some extra help in calming things down, GABA can help. While GABA does not readily cross the blood-brain barrier, you have many other options available for regulating or boosting GABA, if GABA as a supplement doesn’t work for you. I suggest trying a GABA supplement first at a dose of 500 mg. Or try one of the readily available GABA supplements made by major supplement makers containing PharmaGABA™. Another safe option for regulating GABA levels is to use a vitamin or supplement which influences the way GABA works in your brain. Check the “Available Forms” section of this article for details.

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Ginkgo Biloba Gingko biloba extract has been shown to boost alertness, concentration, focus and memory Ginkgo biloba (Ginkgo or Maidenhair) is one of the oldest species of trees on earth. Scientists consider it a “living fossil” dating back 270 million years.289 It has continued to survive even after major extinction events. Gingko tress can grow to 130 feet (39.6 meters). Some Ginkgo trees in China are thought to be over 2,500 years old. And a 3,000-year-old tree reportedly stands in the Chinese province of Shandong. Four Ginkgo trees survived the atomic explosion in Hiroshima. Only 1,130 meters from the bombs epicenter. Gingko biloba has been used for medicine in China for several millennia. In the oldest Chinese Materia Medica (2800 B.C.), Ginkgo biloba was recommended for asthma, swelling of the hands and feet, coughs, vascular disorders, aging and for the brain.290 An extract of Gingko leaves called EGb 761 is standardized to 24% flavone glycosides (flavonoids) and 6% terpenes (ginkgolides and bilobalides). This Gingko extract regulates neurotransmitters, protects from brain cell degeneration, increases blood vessel microcirculation (blood flow in the smallest of blood vessels). And has antioxidant activity.291 But there’s more… Ginkgo biloba helps: •

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Neurotransmitters. Gingko biloba can increase dopamine in the brain. Ginkgo acts as a monoamine oxidase inhibitor (MAOI) which reduces levels of monoamine oxidase (MAO) in the brain. MAO breaks down dopamine.292 One of the benefits of boosting dopamine is to reduce anxiety.293 And to treat ADHD.294 Cerebral Circulation. Ginkgo biloba increases cerebral blood flow. Improving oxygen and glucose availability to neurons for neuronal health. Improving memory, recall, cognition and learning.295, 296 Neuroprotection. Ginkgo Biloba helps boost cerebral blood flow, reduces oxidative stress by eliminating free radicals, and increases nitric oxide which dilates blood vessels.297

As a nootropic, Ginkgo has been shown to be particularly effective in elderly memory loss, slow thinking and reasoning, and tinnitus. One study shows significant improvement in Parkinson’s and Alzheimer’s patients.298 How does Ginkgo Biloba Work in the Brain? Ginkgo Biloba boosts brain health and function in several ways. But two in particular stand out. 1. Cerebral circulation. Ginkgo boosts several brain functions by improving blood circulation in

the brain. A study in the Department of Radiology at Johns Hopkins University School of Medicine used MRI’s to measure blood flow in 9 healthy men. MRI’s were done before and after the men took Gingko Biloba Extract 60 mg twice a day for 4 weeks. The study concluded that overall, all regions of the subject’s brains showed a significant change in cerebral blood flow after using Ginkgo.299 2. Cognition and mental performance. Gingko is well known as a memory booster in the nootropics community. Studies have shown Ginkgo helps attention, mood and processing speed. One large study at Liberty University in Lynchburg, Virginia was conducted with 262 healthy adults. This 6-week, double-blind, placebo-controlled trial had volunteers taking 180 mg of Ginkgo biloba extract, or a placebo daily for 6 weeks. The subjects were put through several standardized tests. At the end of the 6-week trial, those using Ginkgo showed significant improvement in verbal and visual recall and memory.300 How things go bad As we get older, our brain chemistry and energy metabolism changes. Blood vessels in our brain shrink and get narrower. Preventing the free flow of oxygenated blood to neurons. Toxic waste and free radicals accumulate within brain cells. ↓ Memory, recall, reaction time and mood diminish ↓ Critical neurotransmitters decline ↓ Chronic stress reduces memory capacity All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. But even if you’re not concerned with the effects of aging, Ginkgo biloba can help. Ginkgo Biloba benefits Research from hundreds of studies have shown that Ginkgo biloba will: • • • • • • • •

Improve memory and cognition301 Increase reaction time Restore the availability of dopamine and other neurotransmitters Improve cerebral blood flow Reduce stress302 Boost mood Help repair brain cells Act as an antioxidant to eliminate free radicals

How does Ginkgo Biloba feel? Gingko improves circulation in your body and brain. Thinking, reaction time, energy, and memory should improve. Cold hands and feet are often an indication of poor circulation and Ginkgo could help. Ginkgo has a reputation for helping reduce the symptoms of tinnitus. And it’s also developed a good rep for helping erectile dysfunction (ED) in men. Many neurohackers report it takes several weeks of continued use of Gingko to experience all the benefits this healing herb provides. The Research Age-related cognitive decline is expected as a normal part of aging in our society. This decline can lead to difficulty performing everyday activities like concentrating on what your loved one is saying. Or remembering to attend a family function you’ve been looking forward to for months. This decline will affect your quality of life and affect your mood. And it’s happening to younger and younger people. But many of us in the nootropics community refuse to accept cognitive decline as “standard”. Note: One important consideration I found in the research on Gingko Biloba. Some of the findings have been contradictory. Some indicating that Gingko does not work. But the overwhelming impression we got from looking at decades of research was that Gingko Biloba takes a while to work. Often it can take many months of supplementation to see results. And extracts work far better than plain, powdered, ground Ginkgo. Ginkgo Biloba Improves Cognition Researchers in Germany set out to study the effects of Ginkgo Biloba in healthy adults. This randomized, double-blind, placebo-controlled trial worked with 66 health volunteers for 4-weeks. One group was given a placebo, and the other group took 240 mg of Ginkgo Biloba extract daily. At the end of the trial, those taking Ginkgo Biloba extract saw significant improvements in their “selfperceived” mental health and quality of life. They performed far better on action and reaction tests. And reported a significant improvement in mood compared to those in the placebo group.303 Ginkgo Biloba Improves Quality of Life Another study with 1,570 men and women in England took either no dietary supplement or 120 mg of Ginkgo Biloba extract daily for 4, 6, or 10 months. Participants who took Ginkgo extract experienced improvement in activities of daily living, mood and alertness compared to the control (who took nothing). Activities of daily living included multi-tasking, completing household tasks, concentrating during a conversation, remembering important dates, and giving and following directions.

Measures of their mood included ratings of anxiety, depression, energy, drowsiness, sadness, and happiness. Alertness factor rated whether they felt alert, clumsy, dizzy, relaxed, and tired. Participants in this study who took Ginkgo Biloba extract the longest reported the greatest improvement in all ratings measured. 10 continuous months of supplementing with Ginkgo extract was more effective than 4 months. Their life improved even more the longer they took Ginkgo Biloba extract.304 Gingko Biloba Improves Attention and Memory Researchers at the University of Northumbria in the UK set out to determine if a single dose of Gingko would improve attention and memory in healthy volunteers. This placebo-controlled, multi-dose, double-blind trial worked with 20 people. Participants were given either a placebo or single-dose of Gingko Biloba extract of 120, 240 or 360 mg. They were tested for their speed of attention, attention accuracy, memory speed and quality of memory. They were tested before the dose or placebo, and again at hours 1, 2.5, 4, and 6 hours. The scientists reported that Ginkgo improved multiple cognitive performance measures. Most dramatic were with “speed of attention”. And results were better with the highest dose of 360 mg compared to the 240 mg dose. This improvement was noted at the 2.5-hour mark. But was still noticeable 6 hours after supplementing with Gingko. The researchers concluded that Ginkgo dosing can produce “sustained improvement in attention in healthy young volunteers”.305 Dosage Notes Recommended dose of Gingko biloba is 40 mg 3-times per day. But daily dosage can range from 120 – 600 mg depending on the disorder being treated. Most Ginkgo biloba products claim that a minimum of 4 weeks is required to achieve a boost in focus, memory and concentration. Side Effects There is the potential for an increased risk of bleeding when Ginkgo biloba is used concurrently with antiplatelet agents (e.g., aspirin, clopidogrel (Plavix®)), anticoagulants (e.g., warfarin (Coumadin®), enoxaparin (Lovenox®), heparin) or herbs with coumarin constituents (e.g., angelica, anise, capsicum, celery, chamomile, clove, danshen, garlic, ginger, horseradish, licorice, onion, papain, red clover). Hypomania has been reported in patients with depression when Ginkgo leaf extract was used in combination with fluoxetine (Prozac®)/buspirone (BuSpar®), St. John’s wort, and melatonin. Ginkgo leaf extract can alter insulin secretion. So patients taking insulin should monitor glucose levels closely. There have also been reports of seizures associated with Ginkgo use with patients using medication

used to lower seizure threshold. These drugs include propofol (Diprivan®), mexiletine (Mexitil®), amphotericin B (Fungizone®), penicillins, cephalosporins, imipenem/cilastatin (Primaxin®), bupropion (Wellbutrin®), cyclosporine (Neoral®), fentanyl (Sublimaze®), methylphenidate, and theophylline. Ginkgo should be used with caution during pregnancy, due to the potential for increased bleeding risk. Ginkgo should be avoided during breastfeeding, due to a lack of sufficient data. Available Forms Gingko leaf is produced from green, picked leaves grown on plantations specifically developed for pharmaceutical purposes. Ginkgo biloba extract is available in capsules, tablets, concentrated liquids, sublingual sprays, bars and cola drinks. Standardized products should contain at least 24% flavone glycosides and 6% terpenes (ginkgolides and bilobalides). The products most commonly used in clinical trials are Ginkgo biloba standardized extracts EGb 761 (Tanakan) and LI 1370 (Lichewer Pharma). Nootropics Expert® Recommendation Ginkgo Biloba extract up to 120 - 240 mg per day I recommend using Ginkgo Biloba as a nootropic supplement. Your body does not make Gingko biloba on its own. So you must take it as a standardized supplement. Gingko biloba that has not been standardized to at least 24% flavone glycosides and 6% terpenes does not appear to be effective. So make sure you buy a standardized Ginkgo supplement. Ginkgo increases alertness, focus, concentration and memory even in the young and healthy. Many neurohackers report immediate effects of supplementing with Gingko. But others find they need several weeks for the active compounds found in Ginkgo to take effect. I suggest dosing up to 240 mg per day split into 3 doses throughout your day. But please refer to the “Side Effects” section of this chapter before you start using Ginkgo. It’s a powerful supplement and could interact with some medications.

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Ginseng Ginseng is known for calming anxiety, and boosting attention, concentration and memory Ginseng is one of the most popular and well researched herbal medicines in the world. It has been used in North America and Asia for thousands of years. In all, there are 11 species of ginseng. But the name “ginseng” as a nootropic usually refers to either American ginseng (Panax quinquefolius), or Asian ginseng (Panax ginseng). Panax means “cure-all” in Greek. Researchers in thousands of clinical trials have reported on the efficacy of ginseng for; anti-stress, cognition, memory, anti-wrinkle, flu, digestion, diabetes, erectile dysfunction, blood circulation, immune deficiency, menopause, anti-oxidant, cancer and much more. Ginseng is rich in various pharmological compounds. Including a series of polyacetylenes, polyphenolic compounds, acidic polysaccharides, and tetracyclic triterpenoid saponins (ginsenosides). Both American and Asian Ginseng contain ginsenosides which researchers believe are the most active ingredient. Here we are investigating ginseng as a nootropic. Ginseng helps: • •

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Mood and Stress. Ginseng helps improve mood and reduce stress. It works as an adaptogen, reducing adrenal fatigue, boosting GABA and providing an anti-stress effect.306 Neurotransmitters. Ginseng provides neuro-protective effects on the dopaminergic-pathway which can help with ADHD.307 And ginseng is a serotonin and norepinephrine reuptake inhibitor. Working as an antidepressant and helping some symptoms of ADHD.308 Brain Energy. Ginseng acts as an anti-inflammatory by reducing cytokines. And as an antioxidant. Boosting ATP production in mitochondria, in part because this antioxidant effect shields mitochondria.309

Overview Ginseng is the most famous medicinal herb in Asia. It must be grown for 5 years before its harvested. The maturity of the plant influences the density of active compounds beneficial to human health. The term “ginseng” comes from the Chinese word ‘rénshēn’ (person + plant root). Because the root shape of ginseng resembles the legs of a human. “Panax” comes from the Greek ‘pan’ (all) and ‘akos’ (cure). In traditional Asian medicine ginseng was used for many different issues affecting human health. An “over-all” cure. The four largest producers of ginseng are South Korea, China, Canada and the U.S, with Canada being the largest exporter. The largest consumer of ginseng is South Korea.

South Korea also conducts the majority of research on ginseng. With 1,000 scholars who publish at least 100 research papers per year.310 The two primary ginsengs used for brain function are Asian Ginseng (Panax ginseng), and American ginseng (Panax quinquefolius). Ginsenosides increase protein synthesis and the activity of neurotransmitters in the brain. And ginseng stimulates the formation of blood vessels and improves blood circulation in the brain. Which improves memory and cognitive abilities.311 How does Ginseng Work in the Brain? Ginseng boosts brain health and function in several ways. But two in particular stand out. 1. Ginseng boosts physical and mental energy. Many of us deal with a lack of energy and chronic fatigue nearly every day. In today’s world, and particularly in Western society, we’re suffering from mental and physical fatigue. From overworked, stressed students to seniors. But this kind of fatigue is not a natural offshoot of ‘getting older’. Often it’s difficult to pinpoint what exactly is causing this fatigue. And the first thing most of us think of is reaching for an energy drink, caffeine, or a prescription stimulant. While these options may work in the short-term, they don’t produce natural energy in your body. This is where ginseng comes in and saves the day. One double-blind, placebo-controlled trial with 30 healthy young adults demonstrated Panax ginseng’s cognitive benefits. The study found that a single dose of 200 mg or 400 mg of ginseng reduced blood glucose levels. And significantly reduced mental fatigue.312 2. Ginseng improves memory and learning. Most people who use ginseng report feeling more alert. And several trials show Asian ginseng can improve thinking and learning. Some of the research shows Panax ginseng can boost performance on mental arithmetic, concentration, and memory. One example of several that show how ginseng seems to affect memory and learning is by boosting nerve growth factor (NGF) and neurite growth in the brain. This study was done on chicks with the ginsenoside Rb1. The researchers found this ginseng extract significantly potentiated NGF and showed neurite outgrowth.313 How things go bad Our brain chemistry and energy metabolism are constantly changing. And any number of factors from chronic stress to disease and environmental factors can degrade cognitive function. ↓ Memory, recall, reaction time and mood decline

↓ Neurotransmitters and cellular signaling breakdown ↓ Chronic stress reduces memory capacity and overall brain health ↓ Nerve growth factor and neurogenesis decline ↓ Free radicals and inflammation damage brain cells ↓ Immune system is compromised All of these changes can happen at any age. And are certainly contributing factors to age-related cognitive decline. Ginseng benefits Panax ginseng (Asian) and Panax quinquefolius (American) contain a collection of active compounds called ginsenosides. These triterpenoid saponins (plant chemicals) are unique to the ginseng species of plants. And are steroid-like in nature. Here’s a mind-blowing statistic; well over 100 different ginsenosides exist.314 The major ones are designated Ginsenoside Ro, Rb(1), Rb(2), Rc, etc. All are extracted from the rhizome (root) of the ginseng plant. You’ll notice if you’ve reviewed any of the other nootropics listed on my website NootropicsExpert.com, that I usually include a diagram of the active chemical compound in that nootropic. In this case I’m not including the diagram because each compound extracted from ginsenoside is different. Each ginsenoside has a unique effect in your body and brain. And is often even metabolized differently in your digestive system. Other components of ginseng include: 3. Polysaccharide ‘Ginsan’ which is an immune system modulator315. Ginsan is likely what helps tame inflammation in the brain. Which helps a host of cerebral functions like; neurotransmitters working more effectively, prevents apoptosis (cell death), improves memory, mental energy and more. Anti-inflammatories or not talked about much in the nootropics community. And I think in the future you’ll be hearing a lot more about how important they are to cognitive health and function. •

MicroRNA’s which are gene modulators. Researchers have recently identified up to 73 MicroRNA’s in ginseng.316 These tiny non-coding molecules are capable to regulating the gene expression in the DNA of your brain cells. Which is an extremely complex subject in itself. And have the potential to affect nearly everything that happens in your brain.

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Polysaccharides which have anti-cancer effects. Another subject not talked about in nootropic circles. But fundamentally important to brain health.317

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The amino acids L-Arginine and GABA (gamma-aminobutyric acid), and glutamate.318 The neurotransmitter GABA is naturally produced in your brain and provides anti-anxiety and calming effects. Likely why supplementing with ginseng has a calming and anti-anxiety effect.

Several books could be written on how ginseng affects your brain. Including its appetite-suppressant qualities, ability to boost cognition, reducing fatigue, reducing depression, anxiety, stress, improving memory and learning, as a neuroprotectant, and increasing cerebral blood flow. How does Ginseng feel? Supplementing with ginseng should boost your energy levels, both physical and mental. Ginseng has stimulant-like qualities and should help if you’re dealing with chronic fatigue. But unlike standard stimulants, your boost in energy will come with a more ‘relaxed’ feel. Ginseng can boost mental alertness. And thinking should feel quicker and clearer. Recall and long-term memory should improve. Ginseng also boosts your immune system so you may be able to avoid the flu or a cold. Ginseng is particularly helpful for anyone with a compromised immune system. And if you’re living with or working around anyone else who is sick. The Research Much of the research on ginseng comes out of South Korea. And much of this research has been done with Asian ginseng (Panax ginseng). Showing how Panax ginseng improves cognitive function. American ginseng (Panax quinquefolius) has a somewhat different ginsenoside profile from Panax ginseng. And it too shows promise in benefiting human cognition. American Ginseng Boosts Working Memory One double-blind, placebo-controlled trial was conducted with 32 healthy young adults. In this trial, researchers used a highly standardized extract of American ginseng (Cereboost™). Cereboost™ is Panax quinquefolius standardized to 10.65% ginsenosides. This trial used doses of 100, 200 and 400 mg of standardized ginseng. And participants’ mood, cognitive function and blood glucose were measured at 1, 3 and 6 hours after taking the ginseng extract. The researchers found that standardized American ginseng provided a significant improvement in working memory. Reaction time accuracy and ‘calmness’ significantly improved at just the 100 mg dose. And improved with higher doses. The scientists concluded that there was, “robust working memory enhancement following administration of American ginseng”. And these effects are distinct from that of Asian ginseng. The two ginsengs have different psychopharmacological properties that depend critically on ginsenoside profiles.319 The bottom-line of this study is that the kind of ginseng you use makes all the difference.

Panax Ginseng Protects & Fuels Brain Mitochondria A stroke is caused by insufficient blood flow to that part of the brain where the stroke occurs. Lack of blood flow shuts down the oxygen and nutrient supply to brain cells. And things start to break down in the heart of the cell’s energy center - the mitochondria. This study was done in the Neurology Department at Xijing Hospital in China. Researchers wanted to find out if ginsenoside Rd, one of the major active ingredients in Panax ginseng, could protect the brain from stroke. Rats were given ginsenoside Rd and then subjected to a stroke by reducing blood flow to part of their brain. (Note for gratitude journal – I’m thankful I’m not a lab rat). The scientists found this Panax ginseng extract protected the rat brain from stroke. And it appeared to do it by protecting brain cell mitochondria from dysfunction, and apoptosis (cell death).320 Researchers also demonstrated that ginseng activates multiple enzymes in the Krebs cycle. This helps mitochondria extract maximum energy in the form of ATP from glucose fuel.321 Which is one of the reasons why supplementing with Ginseng boosts mental energy. Ginseng Improves Mental Performance Actoprotector is a new term given to natural compounds that increase mental performance. And enhance your body’s ability to withstand physical loads without increasing oxygen consumption.322 Actoprotectors are a new subclass of adaptogen that increase physical performance. And some extracts of Panax Ginseng are considered Actoprotectors. The main difference of Actoprotectors and psychostimulants (caffeine, Ritalin, modafinil, adrafinil, etc.) is that Actoprotectors cause no increase in oxygen consumption or heat production. The result in improved mental and physical performance are similar. But there’s no “crash” in 4 hours like you get from using a stimulant like Ritalin. You don’t experience the same kind of ‘mental load’ when using ginseng.323 Ginseng’s steroid-like phytochemical called ginsenosides are what provide this stimulant-like action in the brain. And an improvement in overall quality of life. One report in 2003 evaluated 9 clinical trials done with humans with ginseng doses from 80 – 400 mg. Study duration spanned 2 – 9 months. And nearly every study evaluated demonstrated some improvement in Quality of Life score.324 Dosage Notes Dosage of ginseng depends on the extract used, and quality of the extract. And results seem to be largely dependent on the quantity used.325 To complicate things even more, ginseng dosage depends on the region where its grown, extract strength, and individual needs.

The Chinese for example recommend 2 grams daily while in Europe, the suggested range is 100 – 400 mg daily. Many naturopaths recommend cycling ginseng. Use it for 3 to 4 weeks and take a week break. Remember, ginseng has steroid-like active compounds. So taking it for extended periods without a break is not recommended. Ginseng has been and continues to be extensively researched. These doses are based on clinical trial data: • • •

For stress, anxiety or fatigue: 1-gram ginseng daily dosed 500 mg twice per day For Type 2 diabetes: 200 mg per day For erectile dysfunction (ED): 900 mg of Panax ginseng 3-times per day

The bottom-line is to stay within the dosage recommended by the ginseng supplement manufacturer. Side Effects Ginseng is a natural supplement and side effects are generally mild. But it can act as a stimulant in some people. Which can cause anxiety and insomnia. Long-term use or higher than recommended doses can cause headache, dizziness and stomach upset. If you’re going to use ginseng you should cycle your dosing. Use the recommended dose for 3-4 weeks and take a week off before dosing again. Women may experience menstrual changes when supplementing with ginseng. Ginseng is NOT recommended by the under-18 neurohacker. Or women who are pregnant or breastfeeding. Ginseng may affect blood sugar levels. So if you’re taking drugs for diabetes, check with your doctor first before supplementing with ginseng. Ginseng can interact with: • • • • •

Blood-thinning medications Antidepressants Antipsychotic medications Stimulants including caffeine, Ritalin, Adderall, modafinil, adrafinil, etc. Morphine

Available Forms Ginseng supplements are made from ginseng root and root hairs. It’s available in dried, powdered, capsule and tablet form. Ginseng is also included in some nootropic stacks and other combination supplement formulas. Some with patented ginseng extracts like Cereboost™, GS15-4, and others.

Experienced users of ginseng seem to prefer American Ginseng (Panax quinquefolius) over Asian Ginseng (Panax ginseng). Each is a unique species of ginseng but both have ginsenosides. But American Ginseng is cultivated under stricter conditions avoiding pesticides and herbicides. And the colder growing climate encourages higher concentrations of the active ingredients in ginseng. When buying American ginseng, look for Panax quinquefolius. And when buying Asian ginseng, look for Korean, red or Panax ginseng. And finally, make sure you buy from a reputable supplement maker. Very recently GNC, Target, Walgreens and Walmart stores in the U.S. were found to contain either contaminants or little to zero ginseng. Walgreens ginseng brand was found to contain nothing but garlic powder and rice.326 Nootropics Expert® Recommendation Ginseng 100 - 400 mg per day I recommend using Ginseng as a nootropic supplement. Your body does not make Ginseng on its own. So you must take it as a standardized supplement. Ginseng is especially helpful for chronic fatigue. And a great way to provide a natural physical and mental energy boost. Ginseng provides anti-anxiety and calming effects. And can boost mental alertness, memory, recall, and learning. Ginseng is a powerful adaptogen that has been used for thousands of years. The ancient Chinese and other cultures used it for overall health. I suggest starting with a dose of 100 mg daily. You can safely boost it to 4-500 mg per day depending on the brand and extract. But remember that ginseng has steroid-like qualities. So make sure you cycle it. Use it for 3-4 weeks and take a week off. And don’t take it late in the day as it may interfere with sleep. Many neurohackers prefer American over Asian ginseng. It has a slightly different ginsenoside profile. And is grown under stricter conditions ensuring quality and safety.

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Gotu Kola Gotu kola has been shown to increase memory and cognition, repair and reverse damage to brain cells, and boost acetylcholine Gotu Kola (Centella asiatica) is often called “the student herb” in Bali. Because it sharpens the mind. Gotu kola extract increases dendrite and axon growth in brain cells which helps memory. Native to the wetlands of Asia, the ancient Ayurvedic medical system used gotu kola like a first-aid kit. It was used to treat mental fatigue, anxiety, depression, memory loss, insomnia, fever, syphilis, hepatitis, epilepsy, diarrhea and asthma. Gotu kola even has a link to longevity. The ancients believed that elephants who ate gotu kola leaves lived longer than those that didn’t. In the U.S. and Europe gotu kola is typically used for varicose veins, poor blood circulation in the legs, to treat psoriasis and help heal minor skin wounds. Gotu kola is rich in triterpene saponosides. A study in Japan showed that one of these triterpenoids called asiatic acid was able to stop the growth of cancer cells.327 As a nootropic, gotu kola has been shown to be particularly effective in elderly memory loss, slow thinking, and reasoning. One study shows significant improvement in Alzheimer’s patients.328 And some of the most exciting new research on gotu kola shows it can spur growth in brain cells. Here we explore all the ways gotu kola can help your brain. How does Gotu Kola Work in the Brain? Gotu kola boosts brain health and function in several ways. But two in particular stand out. 1. Neural dendrite and axon growth. Gotu kola helps increase the length and branches of neuron dendrites. And boosts axon growth. Dendrites are tree-like branches extending out from neurons in the brain. They receive incoming signals from other neurons. Those signals are transmitted from axons extending out from neighboring neurons. Dendrites and axons can change over time, and in response to environmental cues. Learning something new for example cause dendrites to lengthen. But this natural signaling mechanism in your brain’s neurons degrade over time. And several studies have shown how gotu kola can reverse this damage. Scientists at the Oregon Health & Science University in Portland, Oregon did their research with Sprague-Dawley rats. They put Centella ethaniloc extract, a compound in gotu kola, in the rat’s drinking water. The study concluded that axons grew at a faster rate. And the researchers stated that gotu kola extract

was useful for accelerating repair of damaged neurons.329 Another study showed rats given gotu kola leaf extract had an increase of 105% in dendrite growth.330 A very recent study conducted at Northwestern University and published in Nature shows how dendrites are critical in memory formation.331 2. Increase in memory and learning. Gotu kola has been revered for thousands of years for boosting memory. We know that gotu kola extract can increase the availability of acetylcholine (ACh) in the brain. It does it by preventing ACh from breaking down. This boost in memory may also benefit from gotu kola’s ability to boost the growth of neuron dendrites and axons. In one randomized, placebo-controlled, double-blind study done in Thailand, researchers gave 28 people gotu kola extract for 2 months. Daily doses ranged from 250, 500 to 750 mg per day. Cognition in these subjects increased, and they experienced a boost in working memory.332 How things go bad Over the course of your life, your brain will lose 5 – 10% of its weight. It starts in your early 20’s.333 The Framingham Offspring Cohort Study included 1,352 adults who did not have dementia. 7 years after the start of the study they used an MRI to measure participants brain size. And gave them tests to gauge executive function, planning and organizational skills. The researchers found that people with high blood pressure, diabetes, overweight or smoked had faster brain shrinkage. They showed declines in ability to make decisions, plan, organize and remember details.334 ↓ Memory, cognition, learning and recall decline ↓ Neuronal cell death results in shrinking gray matter ↓ Neuroplasticity declines degrading long-term potentiation335 Your brain will shrink regardless of lifestyle. But you can reduce the speed of this shrinkage by using gotu kola. Gotu Kola benefits Research from hundreds of studies have shown that gotu kola will: • • • • • •

Improve memory and cognition Restore the availability of acetylcholine Improve cerebral blood flow Reduce stress Help repair brain cells Eliminate free radicals from within brain cells

How does Gotu Kola feel? Gotu kola improves acetylcholine levels in your brain. It increases blood flow and helps reduce oxidative damage and toxins in brain cells. As a result, you may feel a boost in mental activity. Many say that taking Gotu Kola is like “energizing of the brain”. Particularly during a period of high mental demand. Mental blocks or mental fatigue feel like they’re swept away. Others report dreams seem more vivid and intense. And gotu kola seems to have an anxiolytic (antianxiety) effect as well. The Research Ever been on your way to a party with the thought, “I hope I don’t kill too many brain cells”. Science once believed that the adult human brain could not grow new brain cells. We were born with all the brain cells we’ll ever have. Once those cells were gone, they’re gone for good. Not too long ago a study was published in the Journal of Science. It detailed a discovery by scientists of the daily growth of new brain cells in the macaque monkey. And because of this study, we now know your brain can grow new cells. But the reality is, your brain will lose 5 – 10% of its weight. This shrinkage starts right around your 20th birthday. The good news is you can prevent that shrinkage. And you can do it with gotu kola. Gotu Kola Improves Memory Neurons connect to other neurons at a point called a synapse. Electrical pulses carry chemical messages across this gap. These chemical messengers are neurotransmitters. Each neuron in your brain can form thousands of these links. Dendrites extend out from each neuron to neighboring neurons to receive these messages. Your brain uses these neurons in a type of network. And as one neuron sends signals to another, the synapse between the two gets stronger. The more signals sent between these neurons, the stronger the connection grows. With each new experience, your brain slightly rewires this physical structure. This neuroplasticity determines how your brain is organized. And how memories are formed. Gotu kola extends these neuron dendrites. And helps improve brain neuroplasticity. A study in animal models demonstrated neurite growth using a compound from gotu kola extract.336 And clearly showed how gotu kola works to boost memory. Gotu Kola Improves Mood and Cognition Gotu kola has been revered for thousands of years for its ability to enhance cognition. So researchers in Thailand worked with 28 people in a placebo-controlled, double-blind trial to put some science behind this reputation.

Each participant in this study received an extract of gotu kola at various doses ranging 250, 500, and 750 mg once per day for 2 months. The study showed the higher dose of gotu kola enhanced working memory and mood.337 Researchers in India set out evaluate the nootropic value of gotu kola. Three-month old Swiss albino mice were given doses of gotu kola extract for 15 and 30 days. The researchers found that gotu kola increases acetylcholine activity. And increased dendrites in the mice hippocampus. Showing that gotu kola can promote higher brain function.338 Dosage Notes Recommended dose of gotu kola standardized extract is 50 – 250 mg taken 2 or 3 times daily. Standardized extracts should contain 40% asiaticoside, 29 to 30% asiatic acid, 29 to 30 % madecassic acid, and 1 to 2% madecassoside. In human studies in people with venous insufficiency (poor blood circulation in the legs), 90 – 180 mg daily worked well for these patients. As a tincture (1:2 w/v, 30% alcohol): 30 to 60 drops (equivalent to 1.5 to 3 mL, there are 5 mL in a tsp.), 3 times daily. Side Effects Side effects are rare with gotu kola. But may include skin allergy and burning sensations if you’re applying it on your skin. Taken internally, side effects could include headache, upset stomach, nausea, dizziness and drowsiness. Gotu kola has been used in some studies that lasted up to one year. But please note that gotu kola has the potential to be harmful to the liver. Some medical authorities caution that it is best not to use gotu kola for more than 6 weeks without talking to your doctor. Asiaticoside, a major part of gotu kola, has also been linked with tumor growth in mice. If you have a history of precancerous or cancerous skin lesions, such as squamous cell, basal cell skin cancer, or melanoma, you should not use gotu kola. And if you have liver disease, or take medications that affect the liver, you should not take gotu kola. Again, check with your doctor if you take any prescription medications, or often take over-the-counter pain relievers that could affect your liver. Available Forms Gotu kola is available in teas, dried leaf in powder form, tinctures, capsules, tablets and ointments. Nootropics Expert® Recommendation Gotu Kola extract up to 600 mg per day I recommend using Gotu Kola as a nootropic supplement.

Your body does not make gotu kola. So you must take it as a supplement to get its effects. This ancient herb has a long history of safe use as both an herbal remedy, and food throughout much of southeast Asia. Here in the West, gotu kola is mostly used for healing varicose veins and skin conditions. But its overlooked as a nootropic. Gotu kola can improve your mood and memory. And protect your brain from free radicals and the toxins you’re exposed to everyday. Gotu kola as a nootropic has the potential to keep you mentally sharp for life. And if the ancients were right, may even help you live longer. You can even rid your day of stress and anxiety by sipping gotu kola tea. Or use a supplement as a cognitive enhancer. If you’re using gotu kola extract and dosing up to 600 mg per day, split your dose into 200 mg 3-times per day.

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Huperzine-A Huperzine-A improves cognition, memory, learning, recall, is an antioxidant, helps neuroplasticity, and protects against glutamate-toxicity Huperzine-A (Hup-A) is a water-soluble alkaloid nootropic derived from Chinese Club Moss (Huperzia serrata). This plant is native to southeast Asia. And has been used in traditional medicine for millennia to treat skin conditions, muscle problems and to boost blood circulation. Huperzine-A is a reversible acetylcholinesterase (AChE) inhibitor. Which means it prevents the breakdown down of acetylcholine (ACh). Boosting short-term memory and long-term brain health. Huperzine-A is also a NMDA receptor antagonist. This glutamate receptor’s job is to control synaptic plasticity and memory function. Which is a positive thing. But blocking its function can also be effective at times. By preventing damage from too much acetylcholine. And blocking the toxicity from certain nerve agents.339 This combination of boosting acetylcholine and blocking NMDA receptors requires a fine balance. And could explain why it’s beneficial to cycle the use of Huperzine-A. To maintain the delicate balance of neurochemistry in the brain while realizing Huperzine-A’s benefits. Huperzine-A vs. Huperzia serrata: What’s the Difference? Huperzine-A (Hup-A) is produced in the lab from Huperzia serrata (Chinese Club Moss). Huperzine-A is a standardized compound found in this naturally occurring plant. Note that Huperzine-A and Huperzine serrata are NOT the same supplement. Some nootropic supplement stacks substitute genuine Huperzine-A with Huperzia serrata. All the research I’ve seen uses Huperzine-A in their trials. Not Huperzia serrata. Look for nootropic stacks with genuine Huperzine-A on the label. Or sold as a stand-alone supplement. And avoid stacks or supplements called Huperzine serrata. How does Huperzine-A Work in the Brain? Huperzine-A boosts brain health and function in several ways. But two in particular stand out. 1. Huperzine-A acts as an acetylcholinesterase (AChE) inhibitor. AChE is an enzyme that breaks down the important neurotransmitter acetylcholine. So Hup-A helps prevent this breakdown. Allowing more acetylcholine to be available which improves memory and learning. Scientists at the Weizmann Institute in Israel uncovered how Huperzine A works to block acetylcholinesterase (AChE). They made a 3-D image of the structure of the AChE molecule. And found a deep chasm, called the “active-site gorge”. The scientists found the active-site gorge acts like a guide to funnel acetylcholine into the interior of the

enzyme where it is cut apart prior to recycling. This is how AChE blocks acetylcholine. The study revealed that Huperzine-A has the unique ability to fit into this active-site gorge. Like a key into a lock. And appears to bind more tightly and specifically to AChE than other AChE inhibitors. This ability for Huperzine-A to take acetylcholine’s place within the AChE enzyme is how more acetylcholine is made available in the brain. Professor Joel Sussman said, “It is as if this natural substance were ingeniously designed to fit into the exact spot in AChE where it will do the most good.”340 2. Huperzine-A also plays a neuroprotective role. Researchers discovered that Hup-A prevents glutamate-induced toxicity. Protecting hippocampus and other cerebral neurons from cell death caused by the amino acid glutamate.341 In addition to protecting from glutamate-induced toxicity, Huperzine-A also promotes new dendrite growth in neurons.342 How things go bad As we get older, our brain chemistry and metabolism changes. ↓ Acetylcholine levels decline ↓ Concentration, attention and mental agility decline ↓ Nerve growth factor declines ↓ Free radicals damage brain cell mitochondria All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Huperzine-A can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting the availability of acetylcholine in your brain. Huperzine-A benefits Huperzine-A boosts acetylcholine Huperzine-A boosts levels of available acetylcholine in the brain by blocking the effect of the enzyme acetylcholinesterase (AChE). Acetylcholine (ACh) is critical for encoding new memories, reasoning, concentration, cognition, and neuroplasticity. Not enough ACh can result in diseases like ADHD, Alzheimer’s and other neurodegenerative diseases. Huperzine-A’s benefit as a nootropic can boost short-term mental performance like attention and memory. And even helping your brain for long-term brain health.

Huperzine-A is an antioxidant Huperzine-A supports brain cell mitochondria. The main energy centers of each cell. It reduces free radical damage by acting as an antioxidant. Free radicals degrade mitochondria and their function. Studies have shown that Hup-A enhances the activities of other antioxidant enzymes as well.343 Huperzine-A resists beta-amyloid dysfunction Huperzine-A boosts neuron resistance to beta-amyloid induced dysfunction that could lead to diseases like Alzheimer’s. Beta-amyloid affects ATP levels in mitochondria. Hup-A protects against this damage.344 Huperzine-A prevents glutamate toxicity Huperzine-A protects brain cells from glutamate toxicity. Too much of the neurotransmitter glutamate has been associated with brain cell degeneration. And other cognitive dysfunction and behavior. Hup-A seems to slow down this glutamate toxicity at least partly by acting as a NMDA receptor antagonist.345 Huperzine-A increases nerve growth factor Huperzine-A boosts nerve growth factor (NGF) in the brain. NGF is critical in brain cell development, maintenance and repair. Declines in NGF-levels in the brain are associated with Alzheimer’s and other neurodegenerative diseases. Studies show Hup-A not only prevents this drop of NGF from happening. It actually helps boost the production of NGF.346 How does Huperzine-A feel? Nootropics users report Huperzine-A provides a boost in mental energy. Without the side effects normally associated with a stimulant. Improved cognition and clear thinking are common when using Hup-A. Many report a boost in shortterm memory. Recall is better in the long-term. And some with Alzheimer’s report the progression of the disease slows down. Instead of advancing. You should be able to experience the effects of Huperzine-A soon after you take it. It’s water-soluble so it’s digested and enters your cells quickly. One thing to note is; Huperzine-A has a long half-life. In other words, it does not leave your system nearly as quickly as most other nootropics. So many neurohackers restrict their use of Hup-A to a couple of times per week. The Research Huperzine-A is most known for boosting acetylcholine (ACh) in the brain. Efficient ACh neurotransmission is critical for learning, memory and attention. Reduced levels of ACh are associated with declines in cognition and memory. And are implicated in several neurodegenerative diseases including Alzheimer’s, Parkinson’s, ALS and others.

Huperzine-A supplementation helps even in those with no sign of brain disease. It can enhance attention and memory in most looking to boost cognition. Huperzine-A Provides Protection in Chemical Warfare If you ever find yourself in a warzone, you may want to stock up on Huperzine-A. Researchers at the Walter Reed Army Institute of Research in Washington D.C. are investigating Huperzine-A’s potential as a pretreatment to protect soldiers against chemical warfare nerve agent poisoning. One of the studies conducted at Walter Reed looked at Huperzine-A’s protective potential. Scientists found Hup-A to be twice as effective in protecting against the lethal effects of the nerve agent soman as the leading drug in that role called physostigmine. Huperzine-A’s effects lasted for six hours compared to only 90 minutes for the drug.347 Huperzine-A Improves Learning & Memory This study is verification of using Huperzine-A as a nootropic at any age. Researchers in China selected 68 students who complained of bad memory. And their learning performance was getting worse in school. In this double-blind, placebo-controlled trial students were given either 100 mcg of Hup-A or a placebo for 4 weeks. At the conclusion of the trial, researchers found that the students using Huperzine-A scored higher on memory testing than those who took the placebo.348 Huperzine-A Improves Cognition Much of the research on Huperzine-A has been done in China. And many of the studies have been with patients suffering from neurodegenerative diseases like Alzheimer’s. One study done in Shanghai worked with 200 patients who met the criteria for having Alzheimer’s Disease. Researchers gave one group of patients 300-500 mcg of Hup-A daily for 8 – 24 weeks. The other group got a placebo. The results of the study showed that Huperzine-A’s effects increased over time. The patients that used Hup-A showed significant improvements in cognition, orientation, attention, memory, mood and behavior.349 Dosage Notes Recommended Huperzine-A dosage is 50 – 200 mcg per day. Hup-A is water-soluble, so you don’t need to take it with a meal, or healthy fat like some nootropics. Huperzine-A is typically sold as 50, 100, or 200 mcg tablets or capsules. Several retail nootropic stacks often include Huperzine-A in their formula. So you should not supplement with more Hup-A while using these pre-made stacks.

Since Huperzine-A has at least a 12-hour half-life most neurohackers prefer cycling. This means using Hup-A every 2nd day or even only twice per week. Huperzine-A is also available as an injection for therapeutic use. Typically used to treat diseases like Alzheimer’s. Or the muscle weakness condition called myasthenia gravis. Side Effects Huperzine-A can be toxic if used in larger than recommended doses. Or if you already have too much acetylcholine(ACh) in your system. Remember, Hup-A boosts levels of ACh. Side effects with Huperzine-A are rare but can include symptoms similar to choline-overload like fatigue, nausea, vomiting, diarrhea, insomnia, anxiety, dizziness, thirst and constipation. Very rarely will Huperzine-A cause cardiac arrhythmia. Symptoms of acute toxicity are similar to those of other cholinergic inhibitors. And can include fatigue, muscle tremors, drooling, tears, bronchial mucous and incontinence. Do not use Huperzine-A if you’re dealing with epilepsy. And if you have heart disease, use Hup-A with caution. It can slow heart rate. Huperzine-A may make asthma or emphysema worse. Because it can cause mucous in the lungs. The same goes for those dealing with urinary tract or reproductive system blockages. It can cause mucous buildup there as well. An important note for Alzheimer’s patients: Huperzine-A can increase the effects of drugs you may already be taking. Talk to your doctor before trying Hup-A. Available Forms Huperzine-A is sold in tablet or capsule form. Tablets and capsules are usually 50 – 200 mcg each. Some ready-made nootropic stacks include Huperzine-A in their formula. Huperzia serrata is simply raw, powdered Chinese Club Moss and should be avoided. It’s not standardized so you don’t know how much you’re getting. And it’s NOT the same as Huperzine-A. Nootropics Expert® Recommendation Huperzine-A 200 mcg per day I recommend using Huperzine-A as a nootropic supplement. Your body does not make Huperzine-A on its own. So to get its benefits you must take it as a supplement. Huperzine-A is especially helpful for those suffering from cognitive dysfunction caused by diseases like Alzheimer’s.

Huperzine-A is also particularly useful to students and executives who want to boost cognition, learning and memory. Huperzine-A is a fast-acting nootropic that can also help prevent brain degeneration later in life. Huperzine-A does have a long half-life so you may want to cycle it. Either take it every 2nd day, or even twice per week. The benefits are long-lasting and will stay with you.

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Iodine Iodine improves energy levels, cognition, memory and mood Iodine is an essential trace element that combines with the amino acid tyrosine to form thyroid hormones T4 and T3. Thyroxine (T4) contains four iodine atoms, and triiodothyronine (T3) contains three iodine atoms. Iodine deficiency is recognized as the most common cause of preventable brain damage in the world. Even moderate deficiency results in a loss of at least 10 – 15 IQ points.350 And the reason I’ve added iodine to our list of essential nootropics. Insufficient iodine is not only a problem in developing countries. Studies have found even in Western countries; iodine deficiency has become a critical health problem.351 Your thyroid gland absorbs iodine from your blood supply to make and release thyroid hormones. Your thyroid affects every cell in your body and brain through the hormones T4 and T3. Within your brain, T4 is converted to T3 by selenium which then affects gene expression controlling metabolism within cells. And activates the catecholamines dopamine, norepinephrine and epinephrine. Malfunctioning thyroid function which is often caused by insufficient iodine results in poor cognition, difficulty learning, problems with recall, depression and anxiety. The most abundant source of Iodine in our diet comes from seafood like kelp, saltwater fish, seal meat, whale meat, oysters, mussels and lobster. Iodine is also found in beans, milk and milk products, eggs, spinach and vegetables grown in or produced from soil rich in iodine. Typically found near coastal areas of the world. The most seriously iodine-deficient parts of the world are mountainous and inland areas. Including much of the agricultural producing areas of Western countries like Australia, Canada, USA and Europe. Nearly all of your body’s functions in nearly every tissue rely on thyroid hormones. Their actions and influence are so wide ranging that you cannot live without them. Thyroid hormones affect brain development, heart rate, lung function, blood function, bone growth, steroid hormone production, including the breakdown of sugar, fat and protein. And even some immune processes. Iodine is even involved in how the other nootropics in your stack are utilized by cells in your brain. The bottom-line is Iodine could be one of the most important additions to any nootropic stack. How does Iodine work in the Brain? Iodine boosts brain health and function in several ways. But two in particular stand out. 1. Iodine is critical for neurotransmitters. Iodine is required for the production of thyroid

hormones T4 and T3. Thyroid hormone receptors in the brain help regulate the production and use of all important neurotransmitters. Not enough iodine results in too little T3 and T4 in your body. Symptoms of inadequate thyroid hormones (hypothyroidism) include insomnia, fatigue, difficulty concentrating, depression, dry skin and hair, cold sensitivity, frequent and heavy periods for woman, and joint and muscle pain. 2. Iodine is required for a healthy immune system. Iodine is antibacterial, antiparasitic, antiviral and has anticancer properties. Your thyroid is the main storage site for iodine. But this mineral is also concentrated in your glandular system including your salivary and sweat glands. Ovaries, breasts, pancreas, cerebral spinal fluid, skin, stomach, prostate and your brain all contain high concentrations of iodine. Iodine is a powerful method for removing heavy metals and halides like fluoride, chlorine and bromine from your system. These chemicals compete for the same thyroid receptors in cells used by thyroid hormones. So removing these toxins will help thyroid hormones do their job of gene expression and metabolism. How things go bad Iodine is needed by the thyroid to produce the thyroid hormones T4 and T3. Part of the endocrine system, the thyroid secretes hormones that enter your circulatory system. And are transported throughout your body. Every cell has receptor sites for thyroid hormones. Neurotransmitters are used by neurons to communicate with one another. The presynaptic neuron releases a neurotransmitter which then binds to a receptor on the postsynaptic cell. Here we’re going to explore how neurotransmitters relate to the endocrine system and thyroid health. And what can go wrong. Thyroid hormones are involved in the gene expression needed for neurotransmitter release.352 Low levels of iodine result in low levels of thyroid hormones which result in low neurotransmitter levels. Iodine and Serotonin Several studies have shown that low T3 results in reduced levels of serotonin in the brain. If you don’t respond to SSRI’s for depression it could be due to a thyroid hormone imbalance.353 The result is depression. Iodine and GABA In animals and humans there is a direct link between thyroid levels and GABA. Thyroid hormones affect enzymes responsible for synthesis and degradation of GABA, levels of glutamate and GABA, GABA release and reuptake, and GABA(A) receptor expression and function.354 GABA is your brain’s natural Valium. GABA can help turn off stress after you get upset. Or even prevent a stress response in the first place. Low iodine results in low levels of thyroid hormones

affecting GABA. Which can lead to depression or anxiety. Iodine and Dopamine Thyroid hormones play a role in dopamine release in the brain.355 One study showed that an imbalance between thyroid hormones and dopamine could be responsible for restless leg syndrome.356 Iodine and Acetylcholine Thyrotrophic-releasing hormone (TRH) increases acetylcholine (ACh) synthesis.357 One study showed that those with hypothyroidism had significantly decreased acetylcholine in the hippocampus. And that administration of T4 normalized ACh levels.358 Insufficient iodine can result in hypothyroidism. And negatively affect ACh synthesis in the brain. Affecting cognition, memory, learning, recall and mood. Not enough iodine in your diet negatively affects neurotransmitters in your brain. And can result in depression, brain fog, anxiety, learning and memory problems, and ultimately lead to neurodegenerative diseases like Alzheimer’s and Parkinson’s. Iodine benefits Most neurohackers associate Iodine with the thyroid because Iodine is needed to produce thyroid hormones T4 and T3. But Iodine is also concentrated in your salivary glands, stomach, breasts, ovaries, eyes and in your brain. Deficiency in Iodine in any tissue will cause problems in that area of your body. And weaken your immune system. Symptoms of low Iodine show up as brain fog, skin problems, fibroids, fibromyalgia, and chronic fatigue. Iodine can kill bacteria, fungal infections, and viruses. Iodine will remove fluoride, chlorine and bromine.359 And helps your body detox heavy metals like mercury and cadmium that other detox methods can’t remove. Iodine helps prevent and even reverse breast cancer. And helps prevent mental retardation in young children. Your brain needs sufficient Iodine for cognition through several mechanisms of action. This essential element is involved in gene expression that controls the synthesis of neurotransmitters in your brain. And how they work. Iodine helps remove fluoride throughout your body including your brain. Studies show that fluoride can damage your brain, reduce intelligence, and impair memory. Fluoride has even been associated with dementia according to a study by The National Academies of Science, Engineering and Medicine.360 One recent study showed that water fluoridation in England is linked to higher rates of underactive thyroid.361 One of the simplest things you can do to boost cognition and your thyroid is to stop using fluoridated water and toothpaste. And start supplementing with Iodine to remove the fluoride toxicity

and boost thyroid health. Iodine Deficiency Disorders are considered one of the biggest worldwide public health problems today. Studies around the world show none of us are immune from Iodine deficiency. Estimates range from 10 – 90% of the world population don’t get sufficient Iodine depending on where you live.362 Adding Iodine to your stack if you are deficient is one of the easiest and least expensive ways to prevent and even cure a host of health problems. Including boosting cognition and memory. How does Iodine feel? Many neurohackers report an increased level of focus, energy, memory, and cognitive ability when supplementing with Iodine. You should also experience improved quality of sleep. And have an overall improvement in mood. Others report a profound difference in energy levels, they are more alert, and fatigue in the afternoon disappears. A few even report a significant improvement in tinnitus. The Research One of the most common reasons we use nootropics is to boost memory and mental energy. Memory loss drastically reduces quality of life. And simple brain fog makes it difficult to accomplish the simplest of tasks. Research has shown that Iodine is involved in memory, learning and cognition on several levels. And supplementing with Iodine is one of the most fundamental things you can do to boost cognition. Iodine raises the world’s IQ The world’s greatest concentration of iodine deficient countries in the 1990’s was the former Soviet republics of Central Asia. Worldwide, about 2 billion people or a 3rd of the world population get too little iodine. Studies show that iodine deficiency is the leading preventable cause of mental disorders. Even moderate deficiency lowers intelligence by 10 – 15 IQ points. The most visible and severe effects manifest as goiters, dwarfism and cretinism. Ever hear someone use the derogatory term “cretin” to describe someone with low intelligence? Cretin describes a child born and raised with severe mental disabilities, small stature and weakness all due to not enough Iodine in the mother’s diet when she was pregnant. In Japan, people get Iodine from seafood, seaweed, vegetables grown in Iodine-rich soil or animals that eat grass grown in that soil. But even in wealthy nations like the USA and the UK, people still need to supplement. Usually by using iodized salt. Or adding it to their stack as a supplement. According to Dr. Gerald Burrow, a former dean of Yale’s medical school, “For 5 cents per person per year, you can make the whole population smarter than before”. Simply by adding iodine to the salt

supply. Back in the old Soviet republic, Kazakh children were stunted compared to same-age Russian children. A survey of 5,000 households in 1996 found that 10 percent of children were stunted. And iodine deficiency identified as the main culprit. In Kazakhstan, Turkmenistan, Tajikistan, Uzbekistan, and Kyrgyzstan campaigns were run promoting iodized salt. Salt companies were persuaded to add iodine to salt before putting it in stores. In Kazakhstan in 1999, only 29% of households were using iodized salt. Now, 94% of households are. And in 2007, the United Nations certified the country officially free of iodine deficiency disorders. In raising the world’s IQ, the secret’s in the salt.363 Iodine deficiency and ADHD A 10-year study conducted in Italy investigated children born to 16 women from an iodine-deficient area (Area A) and 11 control women in an iodine-sufficient area (Area B). ADHD was diagnosed in 11 of the 16 children born in Area A but none in Area B. Total IQ score was nearly 20-points lower in Area A children compared to Area B. The researchers noted that the prevalence of ADHD in children born in Area A could only be compared to similar children with a resistance to thyroid hormones. And that iodine-deficiency was the likely cause of ADHD due to a critical reduction in intracellular thyroid hormone T3 available to the developing brain.364 Dosage Notes Recommended Iodine dosage is very difficult because everyone needs different amounts based on your body’s ability to use the Iodine. And the level of exposure you have to daily toxins like fluoride, chlorine, and other halides. If you are dealing with a severe health problem, then your dosages would need to be higher that someone trying to maintain good health. Maintenance and for optimal cognition – Natural health doctors have been recommending up to 50 mg of Iodine per day. But I’ve since revised my recommendations based on the latest research and potential health problems caused by iodine toxicity. The maximum adult dosage for adult is 1 mg Iodine per day. Recommended maintenance dosage is the same. Cancer – Cancer is a result of mutated cells. Iodine is critical for the P53 gene which prevents damaged cells from dividing.365 Iodine and selenium helps P53 do its job of eliminating abnormal cells. Cancer patients have used 50 – 300 mg of Iodine per day successfully. Supporting supplements to take with Iodine include:

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Selenium – 200 mcg per day. Selenium is required for the production of T3. And assists in detox. Vitamin C – 2,000 – 5,000 mg per day helps support thyroid symporters which transport thyroid hormones through the body including across the blood-brain barrier. And assists in detox. Magnesium – 400 mg per day. (See my chapter on Magnesium as a nootropic).

Iodine is fat-soluble and should be taken with food particularly if you have a sensitive stomach. The supporting supplements can be taken at the same time as your Iodine dose. Iodine should be taken early in the day because it can increase energy levels so much you could have problems sleeping. Side Effects Most forms of Iodine can cause diarrhea and bloating. Particularly at higher doses. Those with a sensitive stomach could experience stomach pain and is the reason I suggest taking Iodine with food. It is also possible to overdose on Iodine. So please start at a lower dose and see how your body reacts. Symptoms of Iodine overdose include abdominal pain, delirium, fever, vomiting and shortness of breath. Iodine is a powerful method for removing toxins and heavy metals from your body which can also produce unpleasant effects. If you experience flu-like symptoms when starting Iodine its very likely you’re feeling the effects of toxins being flushed out of your cells and your body. For more on Iodine toxicity you can browse an extremely poorly formatted, very long post about Iodine on the Toxicology Data Network. Available Forms Iodine is sold in many forms but the main thing to look for; does the product contain both Iodine and Iodide. Your body needs both forms. Breasts look for Iodine and the thyroid needs Iodide. Contrary to some sources; your body cannot convert supplemental Iodine to Iodide. Also important is to find a product that provides milligram (Mg) doses vs. microgram (Mcg) amounts. Mcg doses will offer very little health benefit. And are much more expensive compared to Lugol’s. Recommended forms • • • •

Lugol’s liquid – Iodine/Potassium Iodide – 2% and 5% solutions. 2% solution is 2.5 mg/drop and 5% solution is 6.25 mg/drop Iodoral – Lugol’s formula in pill form – Iodine/Potassium Iodide – 12.5 mg and 50 mg Biotics Research Iodizyme – 12.5 mg per tablet of Iodine/Iodide Tri-Iodine by Vitaminlife – 12.5 mg per tablet of Iodine/Iodide

Other forms not recommended •

“Nascent Iodine” which is iodine in its atomic state and is a very low dose. Not enough to detox heavy metals, fluoride, bromine and chloride. Or to saturate tissues.

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Iosol which is Iodine only, and the micro doses have the same issues as Nascent Iodine Prolamine which has 3 mg of Iodine and 20 mg of Calcium which is too low to detox the body and saturate tissues Pure Encapsulations, Solaray, Source Naturals, Progressive Labs and NOW all offer mcg doses of Iodide only Kelp because of low Iodine status, not being able to determine levels of Iodine and possibly toxic due to arsenic and halides Nootropics Expert® Recommendation

Iodine up to 1 mg per day I recommend using Iodine as a nootropic supplement. Your body does not make Iodine on its own. So to get its benefits it needs to come from your diet. Or you must take it as a supplement. Iodine is especially helpful for those dealing with brain fog, poor cognition and memory, low energy levels and a sluggish thyroid. Iodine is also particularly useful to help rid your body of the daily toxins we’re exposed to every day including heavy metals, fluoride, chloride, bromine, and other halides. While most forms of Iodine are helpful for overall health, keep in mind it’s the thyroid hormones T4 and T3 which influence cognitive health. Thyroid hormones are produced from tyrosine and Iodine. And the production of T3 from T4 requires selenium which should be a part of your stack when using Iodine. I recommend an Iodine supplement which contains both Iodine and Potassium Iodide to boost cognition. Iodine is a fast-acting nootropic that can also help prevent brain degeneration later in life.

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Kava Kava is known for its anti-anxiety and calming effects, improving cognition & memory, and reducing irritability and depression Kava (Piper methysticum) is a small shrub native to the South Pacific islands including Vanuatu, Fiji, Hawaii, and others. And has been safely used by islanders for 3,000 years. Piper methysticum (Piper is Latin for ‘pepper’. And methysticum is derived from the Greek for ‘intoxicating’). In Polynesia and Micronesia, Kava has been traditionally used as a ceremonial drink. Kava is best known for elevating contentment, mood, well-being and a sense of relaxation. Several clinical studies have found kava to be effective in treating symptoms of anxiety. Other studies have shown kava to help improve sleep quality. As a nootropic, kava is used primarily to lower anxiety with a potency rivalling some anti-anxiety prescription drugs. Kava helps: •

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Neurotransmitters. Kava affects brain levels of GABA receptors. GABA is the ‘calming’ neurotransmitter. And an increase in receptor sites for GABA accounts for Kava’s anti-anxiety properties.366 Neuroprotection. Kava provides protective effects against strokes. Two of Kava’s compounds, dihydromethysticin and methysticin are similar in potency to Memantine which is used to treat Alzheimer’s Disease.367 Cognition. Kava improves reaction time and cognitive function. Kavalactones in Kava interact with ion channels in the brain. Influencing neurotransmitter function.368

Kava continues to have a central place in everyday life in the islands where its grown.369 It’s used as a ceremonial beverage in Fiji where it’s commonly given to the Head of State.370 Kava root contains a collection of 6 bioactive compounds called kavalactones (kavapyrones); including kawain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin. Kava also contains small amounts of other alkaloids, flavonoids and glutathione. The presence of glutathione seems to reduce the toxicity of some other kavalactones. Standardized extracts are important in deciding on what Kava supplement to buy to ensure reliability and safety.371 The main compounds in Kava readily cross the blood-brain barrier. And reaches your brain in about 45 minutes after taking the supplement.372 How does Kava work in the Brain? Kava boosts brain health and function in several ways. But two in particular stand out. 1. Kava boosts cognition. Kava relaxes the muscles and mind, but it doesn’t affect cognition the

way other antidepressants and anti-anxiety drugs do. After a review of 10 clinical studies of Kava, scientists at Australia’s Brain Sciences Institute at Melbourne University found Kava did not negatively affect cognition. In fact, some studies on Kava show it “significantly improved visual attention and working memory processes”. The research team stated that Kava’s “enhanced cognition may be attributed to the ability of Kava to inhibit re-uptake of noradrenaline in the pre-frontal cortex”.373 2. Kava relieves anxiety. Several clinical studies have shown that Kava relieves anxiety. California’s Global Neuroscience Initiative Foundation took a look at 24 studies of Kava and other herbal medicines for anxiety. And there was substantial evidence that Kava relieved not only anxiety, but also restlessness and insomnia. They even looked at animal studies that showed Kava has anxiolytic effects “but not sedative or mental impairing” effects “which are typical side effects caused by benzodiazepines”.374 How things go bad Chronic stress, anxiety, loss of neuroreceptors and neurotransmitters can damage your brain. And one of the ways this manifests is memory loss. It comes as no surprise that people with memory loss experience higher rates of anxiety and depression. As verified in one Australian research study.375 ↓ Chronic stress reduces memory capacity ↓ Bioavailability of neurotransmitters decline ↓ Number of neuroreceptors decline ↑ Increase in anxiety destroys quality of life Under conditions of chronic stress your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition, and decision-making all suffer as a result. Kava benefits Kava has a long and proven record of medicinal therapeutic value. Much of the clinical evidence supports the use of Kava in treatment of anxiety. Unlike benzodiazepines, Kava does not have similar sedative and mental impairing effects. And Kava seems to provide this calming effect by increasing the number of GABA-a receptors.376 Kava extracts have also been seen to bind to GABA, dopamine, serotonin and opioid receptors as well.377 This implies that more of each neurotransmitter is available to the brain since their associated receptors are blocked or inhibited by Kava. Kava extracts have also shown antidepressant effects. Some of the trials demonstrating this effect on

depression also noted that Kava raised no safety concerns at the doses and duration studied. Unlike some well-known pharmaceutical antidepressants. Kava has also been shown to boost cognition and attention. In one study researchers stated that Kava’s “enhanced cognition may be attributed to the ability of kava to inhibit re-uptake of noradrenaline in the pre-frontal cortex…” And finally, Kava also prevents and may even treat several types of cancer. Research shows for example that one of the components of Kava, Flavokavain B reduces prostate tumor growth and inhibits cancer.378 And that’s just one of many examples of how different components of Kava can fight cancer in the lung, bladder, and other organs. How does Kava feel? This can be a little complicated so stay with me. Any particular preparation of Kava will contain up to 18 different kavalactones. Each will have some type of psychoactive effect in your brain. And to complicate things even more, there are several distinct strains of Kava grown in Hawaii and the South Pacific today. All with their own unique profiles of kavalactones and as a result, their own subtle differences in effect. In general, supplementing with Kava (Piper methysticum) can make you feel relaxed, enhancing calmness and lowering anxiety while promoting sociability. Higher doses can generate feelings of gentle euphoria, with greater sedation and mild motor impairment. Many neurohackers say that at lower doses, Kava’s effects are a little like those generated by alcohol and certain kinds of anti-anxiety medications. Some users say it works as well as popping a Xanax. You should experience an increase in focus along with a sense of calm. And even though Kava works well as a sleep aid, taking it during the day shouldn’t make you drowsy. The Research Kava has a lot of clinical research to back up its reputation as a nootropic. Research studies have been noted throughout this chapter. Here are two more… Kava as an anti-anxiety therapy A study at the University of Melbourne, revealed that Kava could be an alternative treatment for those suffering from Generalized Anxiety Disorder (GAD). In this 6-week placebo-controlled, double-blind trial, 75 patients with clinically diagnosed GAD were given Kava or a placebo. Participants were given Kava extract tablets twice per day for a total dose of 120 mg kavalactones for

the first 3 weeks. In cases of non-response, the dose was increased to a double-dose twice per day for the 2nd three weeks of the trial. γ-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Kava was well-tolerated. And results showed no significant differences in liver function. One interesting observation during this study was that subjects who had genetic differences in GABA transporters modified their response to Kava. NOTE: This last observation is just another clue on why some people respond to some nootropics different than others. And why we often say that “Your Mileage May Vary” when using a nootropic. At the conclusion of this trial, 26% of the Kava group were considered in remission for their anxiety symptoms compared to the placebo group. Overall, all participants who received Kava, showed a significant reduction in anxiety levels. And one additional finding of this study was that Kava increased the female participants sex drive.379 Kava enhances cognitive performance Researchers conducted a double-blind, placebo-controlled trial with healthy volunteers. The purpose of the trial was to investigate the effects of Kava on emotions and cognitive performance. One group was given a single dose of Kava extract (300 mg). And that single dose led to an increase in “cheerfulness”, improved accuracy and speed in task performance, increased visual attention and a boost in short-term memory. The research team compared the effects of Kava to conventional benzodiazepine-type anxiolytics which tend to impair cognitive performance. The team concluded Kava is a potent anxiolytic agent which can boost cognitive function.380 Dosage Notes Kava extracts are made with a variety of different strengths, and from different source plant material. So it’s difficult to recommend exact dosages. Fortunately, Kava is relatively forgiving as far as dose is concerned. So taking 2-3 times the recommended dose of an extract should cause no issues. Some neurohackers claim that extracts are just not strong enough. And the only way to get the full effect of Kava is to use ground Kava root which can be found at some natural food stores. Make sure it smells fresh (it should have a relatively strong smell). Fresh powder is used to make a cold tea by making a cold water extraction. Fresh powder is soaked in cold water for 15-20 minutes or more, stirring or shaking occasionally. You can then strain out the powder if you like.

If you want to go the capsule route, look for a Kava extract called “WS1490”. For anxiety and other cognitive issues use 300 mg of this extract daily. Preferably split into three 100 mg doses. One dose in the morning, one early afternoon and the last in the evening. You can also choose a Kava extract supplement with 250 mg total kavalactones. You can use this multiple times throughout the day. If you use only a single dose, take it just prior to sleep. Side Effects Kava has a long and proven track record of medicinal therapeutic value. But if you start doing research on Kava, you’ll see reports of possible liver toxicity. Let’s address this right now. Most research shows there is little to no evidence to support this notion of liver damage when using Kava. For example, one large review out of the University of Melbourne included 24 clinical studies. One of the researchers stated, “Of the 435 clinical trial participants taking Kava supplements in our review, some at high doses, no liver issues were reported. Therefore, the current review supports the conclusion that liver toxicity is indeed a rare side effect.”381 For most of the history of the Kava industry, it’s been harvested and prepared by native, Pacific Islanders. Roots are stored in bulk after harvest. And could develop mold or acquire other contaminants. Increasingly, many Kava suppliers harvest and process their Kava using international manufacturing standards such as ISO, GMP and others. And because of the restrictions by first world countries (esp. the European Union) on the importation of raw ingredients, these protocols are now stricter. So when selecting a Kava product, make sure the manufacturer is adhering to good manufacturing practices. Long-term heavy and consistent consumption of Kava could cause a scaly skin rash called dermopathy. This is reversible when Kava use stops. And finally, Kava should not be mixed with prescription drugs. Don’t use Kava if you’re pregnant or breastfeeding. Kava use may make you unable to drive (similar to alcohol). Don’t use Kava if you have liver problems. And avoid combining Kava with Xanax, clonazepam, lorazepam, phenobarbital, and Ambien. Available Forms In the South Pacific, whole Kava root are chewed for their medicinal value. Kava is also available in liquid form, as tinctures, and standardized extracts as capsules or tablets. Nootropics Expert® Recommendation Kava extract 250 - 500 mg per day I recommend using Kava as a nootropic supplement. Your body does not make Kava on its own. So you must take it as a supplement.

Kava is especially helpful for those suffering from anxiety and stress. Studies show it helps stop and reverse the devastating effects of anxiety and stress in your brain, and body. Kava also has a reputation for lifting mood. And doesn’t have the same side effects as prescription antidepressants. And unlike pharmaceuticals like benzodiazepines, Kava boosts cognition and short-term memory. The usual serving of prepared Kava in the South Pacific is 2-4 fluid ounces. Depending on how its prepared, a bilo (coconut half shell) can contain anywhere from 150 – 500 mg of kavalactones. And native islanders often consume several bilos in a Kava drinking session. Although the local Kava Committee has issued an advisory upper limit of 300 mg of kavalactones per day, many Pacific islanders consume far more, without any ill effects.

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L-Carnosine L-Carnosine improves cognition, memory, energy levels, prevents brain cell death, and is anti-aging L-Carnosine (β-alanyl-L-histidine) is a dipeptide of the amino acids beta-alanine and histidine. Carnosine is found throughout your body. The highest concentrations are in high energy demand areas such as your brain, heart and muscles. (Don’t mistake l-carnosine for l-carnitine). L-Carnosine is known as the ‘longevity molecule’. But don’t let that put you off if you’re not concerned about anti-aging. Carnosine levels decrease with age – starting at age 10! And decrease by 63% by the time you reach 70 years.382 It removes heavy metals which accumulate in, and damage brain cells causing diseases like Alzheimer’s.383 And it prevents cross-linking of proteins which cause the neurofibrillary tangles found in Alzheimer’s.384 L-Carnosine is one of the most powerful antioxidants known. It’s a heavy-metal scavenger. It’s a super auto-regulator. And it stands alone when it comes to preventing and reversing advanced glycation end products (AGEs) or cross-linking. And it’s highly concentrated in your brain. Your brain uses l-carnosine to repair tissue and clear away toxins. And increase the energy output of your mitochondria. It suppresses excess immune responses when your immune system is in hyper mode. And it stimulates the immune response if you have a weakened immune system. L-Carnosine even seems to have the ability to normalize brain waves. L-Carnosine fights mitochondrial dysfunction by relieving oxidative stress caused by accumulation of free radicals in cells.385 This not only works in your brain cells. L-Carnosine is used by athletes to achieve better results. Its buffering nature contributes to the acid-base balance in muscles. Researchers have found l-carnosine restores neurotransmitter receptors. Receptors that were damaged from stroke or glutamate toxicity.386 And l-carnosine reduces damage to telomeres. These caps on the end of DNA strands shorten with each cell replication. This natural, ongoing process is used for example in long-term potentiation needed to form memories. L-carnosine slows the rate of shortening of telomeres.387 Some l-carnosine is naturally produced in your body by the enzyme carnosine synthetase. And you can get l-carnosine from food - primarily from red meat and poultry. But a typical meal provides only about 250 mg of carnosine. It’s then quickly degraded in your body by the carnosinase enzyme. This means carnosine from food doesn’t last long enough in your body to provide much benefit. And if you’re a vegetarian, you won’t be getting much carnosine other than what’s naturally produced in your body.

Supplementing with at least 1,000 mg of l-carnosine per day overwhelms that carnosinase enzyme. Allowing you to maintain consistent blood levels of this vital nutrient. How does L-Carnosine Work in the Brain? L-Carnosine boosts brain health and function in several ways. But two in particular stand out. 1. L-Carnosine is critical for brain health. L-Carnosine’s antioxidant, neuroprotective, chelating, and anti-glycation activity not only maintains optimal brain health. This dipeptide can be used to prevent and treat neurodegenerative diseases, diabetes, diseases of the sense organs (i.e. eyes) and cancer.388 L-Carnosine has been shown to reduce oxidative and glycemic stress.389 And it reduces inflammation. L-carnosine reduces the accumulation of b-amyloid plaque which plays a role in cognitive dysfunction and Alzheimer’s. And it helps remove heavy metals that cross the blood-brain barrier and accumulate in brain cells.390 2. L-Carnosine is required for healthy mitochondria. In your brain, you can have thousands of mitochondria in each cell. And they pump out energy in the form of ATP (adenosine triphosphate). 20% of your body’s total ATP is located in your brain. Glycation during this energy production reduces the functionality and efficiency of mitochondria. This is turn can cause apoptosis (cell death).391 Glycation happens when proteins or DNA bond chemically to sugar molecules. These sugar molecules go on to form advanced glycation end products (AGEs). These AGEs are implicated in Alzheimer’s, skin wrinkles, hardened arteries, and reducing the function of most major organs. Including your brain. A study in the Netherland was done to examine the association between AGEs and cognitive function. This population-based study also included 215 people with type 2 diabetes. Researchers tested for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition. The study found there was a direct correlation with markers measured for AGEs and decreased cognitive performance. And the associations were no different between healthy people and those with diabetes.392 Another study out of the University of California determined that l-carnosine was able to prevent AGEs.393 Free electrons are a byproduct of this energy production. These electrons convert oxygen to a highly reactive form capable of damaging brain cells. And wreaking havoc with DNA in the long-term. If left unchecked, it leads to neurodegenerative disease like memory loss, cognition dysfunction, and eventually diseases like Alzheimer’s.

How things go bad As we get older, our brain chemistry and metabolism changes. ↓ ATP levels decline in mitochondria ↓ Cognition, learning, memory and recall decline ↓ AGEs damage brain cells ↓ Free radicals damage brain cell mitochondria All of these changes can happen at any age. And can start at age 10 or earlier (in the case of autism). So l-carnosine supplementation can help for age-related cognitive decline, as well as anyone who wants to boost cognition, learning, recall and memory. L-Carnosine benefits There is a proven high correlation between human lifespan and l-carnosine levels. L-carnosine is highly concentrated in your muscles and brain. And is directly involved in a number of life-extending activities. L-Carnosine helps prevent the buildup of advanced glycation end products (AGEs) that damage mitochondria. And eventually end in premature cell death. It is a heavy metal chelator and works by removing heavy metal accumulation in brain cells. Lcarnosine is an anti-oxidant and pH buffer in muscle cells preventing lactic acid buildup. How does L-Carnosine feel? When you supplement with l-carnosine you’ll notice younger looking skin. And you’ll have more energy. You should experience a boost in cognition and decision-making capability. Thinking could be more fluid and your motivation may see a boost. These changes are reported by neurohackers in their 20’s and 30’s as well as the more senior user. But most of the talk and research on l-carnosine is on its anti-aging and longevity benefits. So what if I told you, it also helps fight the flu? It turns out that the influenza virus raises nitric oxide (NO) and oxygen free radicals such as superoxide anion (O2-). When NO and O2- interact, they form peroxynitrite, the pathogen that causes pneumonia. The excess amount of toxicity and oxygen radicals generated overwhelms your immune system. A study in the American Journal of Therapeutics reports that l-carnitine can put a stop to this overwhelm. And help you avoid or get rid of the flu or cold. And eating chicken soup to make you feel better when your sick is not an ‘old wife’s tale’ after all.

Chicken soup is rich in l-carnosine.394 The Research L-Carnosine improves cognition Animal and human studies suggest NMDA antagonists worsen executive function. This dysfunction is often caused by glutamate toxicity. And if this persists, you end up with diseases like schizophrenia. This double-blind, placebo-controlled study worked with 75 adults with schizophrenia. They were stable in their symptoms at the time of the study. Subjects were randomly selected to receive 2 grams of l-carnosine per day for 3 months. Executive dysfunction, memory, attention and motor speed were assessed at the beginning, and at 4 and 12 weeks. The l-carnosine group performed much better in executive function tests. And were better at strategy with fewer errors than the placebo group.395 L-Carnosine improves autism symptoms in children L-Carnosine enhances frontal lobe function in your brain. And acts as a neuroprotectant. It also works with GABA for an anticonvulsive effect. This double-blind study worked with 31 children with autism for 8 weeks. They were given 800 mg of l-carnosine per day. The scientists then used several autism rating scales to measure results. After 8 weeks of l-carnosine use, the children showed significant improvement in behavior, sociability, communication and vocabulary. The researchers concluded that l-carnosine enhanced neurologic function.396 L-Carnosine is anti-aging In 1965, Dr. Leonard Hayflick found that human cells have a limited capacity to divide. After which they become ‘senescent’. This is now known as the “Hayflick Limit”. Hayflick discovered that your cells go through 3 phases. First is rapid cell division called ‘mitosis’. The 2nd is where mitosis slows. And the 3rd stage is ‘senescence’ where the cell stops dividing entirely. They remain alive for a while and then do a particularly disturbing thing. They commit suicide. This programmed cell death is called ‘apoptosis’. This cell life cycle occurs throughout your body and its trillions of cells. Including in your brain. But what if there was some way to slow down this programmed cell death? Turns out there is. And it’s called L-Carnosine. Researchers at Sydney Laboratory in Australia found that l-carnosine extended cell life. They put cultured aged human cells in a petri dish with carnosine. The cells reverted back to juvenile cells. When they put those same newly rejuvenated cells in a culture that had no carnosine, they reverted back to their old self again. Put them back in carnosine and they got young again.397

This experiment has been done again and again in labs around the world. Establishing l-carnosine as the best anti-aging thing since Ponce de Leon was searching for the Fountain of Youth right here in Florida (where I’m writing this chapter). David Guetta thinks that Miami is “the sexiest city in the world”. Could be that everybody in Miami is using l-carnosine. Dosage Notes Recommended L-Carnosine dosage in 1,000 mg per day. To keep a consistent level of l-carnosine in your body, split your dose into two 500 mg doses. One in the morning and one later in the afternoon. One important note on l-carnosine. When you supplement with l-carnosine it binds to aldehydes. Preventing them from making proteins. The byproduct is lipofuscin. This age pigment is not dangerous. But shows up as brown spots on your brain, skin and other organs. As lipofuscin builds up over time, and this process is accelerated when using l-carnosine, it can interfere with proper organ and cellular functions. This is why we recommend stacking l-carnosine with DMAE and acetyl-L-carnitine (ALCAR). DMAE is a naturally occurring nutrient that boosts available choline. And ALCAR boosts mitochondrial energy production while acting as a neuroprotectant. Both DMAE and ALCAR help flush lipofuscin from your brain and body. So stack your daily dose of 1,000 mg of l-carnosine with DMAE and ALCAR at their recommended doses. L-Carnosine is water-soluble, so you don’t need to take it with a meal, or healthy fat like some nootropics. Side Effects Carnosine is considered extremely non-toxic and safe. High doses can cause insomnia. And l-carnosine can cause a stimulant effect. So take your 2nd dose before evening. Available Forms L-Carnosine comes in powder, capsule, tablet, and liquid form. Most major supplement manufacturers offer 500 mg tablets or capsules. But make sure you read the labels and get l-carnosine from a trusted manufacturer who tests their raw ingredients coming into their plant. Tests during encapsulation and then uses 3rd party testing before shipping their product. And choose a L-Carnosine supplement that is pure and free of toxic “other ingredients”. Avoid magnesium stearate and silicon dioxide in your supplements.

Nootropics Expert® Recommendation L-Carnosine 1,000 mg per day I recommend using L-Carnosine as a nootropic supplement. Your body does make some L-Carnosine on its own from the amino acids beta-alanine and histidine. And you can get small quantities from red meat and poultry. But it’s easily and quickly broken down by the enzyme carnosine synthetase. So to get its benefits, and enough to overwhelm the carnosine synthetase enzyme, you must take it as a supplement. L-Carnosine is especially helpful for repairing brain cells at the mitochondrial level. It removes heavy metals, works as a very powerful antioxidant, and gets rid of AGEs. Advanced glycation end products (AGEs) kill brain cells. Foods that are high in AGEs include roasted, fried, sautéed, and barbecued meats, nuts and tofu. Those fries you had for lunch. Brain cell death. Your natural production of l-carnosine starts to drop at age 10. So anyone will benefit from supplementing with this anti-aging nutrient. L-Carnosine helps control blood glucose levels, prevent Alzheimer’s, wound healing, protects from the side effects of chemo therapy, alcohol-induced liver damage, combatting heart disease, and eye health by protecting or repairing cataracts. L-Carnosine is also particularly useful if you’re dealing with autism or Alzheimer’s. For autism, dose up to 800 mg per day. For Alzheimer’s, dose at least 1,000 mg per day.

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L-DOPA L-DOPA (Mucuna Pruriens) is known for improving brain health, is an antioxidant and heavy metal chelator, improves memory & cognition, lowers symptoms of depression, and boosts libido L-DOPA (levodopa, L-3,4-dihydroxyphenylalanine) is an amino acid synthesized in your brain by the amino acid l-tyrosine. L-DOPA is a necessary precursor to the neurotransmitter dopamine. Called a catecholamine, dopamine is then synthesized into the other catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline). And for a dopamine boost, neurohackers use Mucuna Pruriens, which contains high levels of LDOPA.398 This legume, native to the tropical regions of India, Africa, and the West Indies, and also known as velvet bean, has been used in Ayurveda medicine since 1500 B.C. The ancients used Mucuna Pruriens to treat things like snakebite, intestinal problems, sexual issues, and a melancholy mood. Raising levels of the neurotransmitter dopamine in your brain helps regulate mood and cognition.399 Dopamine and norepinephrine are essential for memory, cognition, and a positive mood. A lack of either of these neurotransmitters can lead to a lower mood state, loss of memory, brain fog, poor energy, and more. And if left unchecked will eventually result in neurodegenerative diseases like Parkinson’s. Mucuna Pruriens vs. L-DOPA: What’s the Difference? Mucuna Pruriens is an extract of the velvet bean plant that grows 3 – 18 meters in height. L-DOPA (levodopa) is generally synthetic and made in the lab. The natural version of L-DOPA from Mucuna Pruriens is generally well-tolerated by most people. And the compounds in the plant are bio-identical to those chemicals naturally made in your body. Not so with synthetic L-DOPA. Synthetic L-DOPA is metabolized into dopamine in your body by an enzyme called aromatic L-amino acid decarboxylase (AADC). And the majority of synthetic L-DOPA will be converted peripherally (not in the central nervous system and brain). This can cause problems. So when used therapeutically, as in treating Parkinson’s Disease, L-DOPA is administered in combination with an inhibitor of peripheral AADC. Drugs like carbidopa (or other AACD inhibitors) ensure most of the L-DOPA is preserved for conversion to dopamine in the brain. And not the rest of your body. This is critical for nootropic users to keep in mind. Chronic, or prolonged use of synthetic L-DOPA can lead to things like dyskinesia. This is a movement disorder where neurological discoordination results in uncontrollable, involuntary movements.400

We’re not telling you this to dissuade you from using L-DOPA. Stick with an extract of Mucuna Pruriens and you should be fine. How does L-DOPA Work in the Brain? L-DOPA boosts brain health and function in several ways. But two in particular stand out. 1. L-DOPA improves memory. It’s metabolized into dopamine in your body by an enzyme called aromatic L-amino acid decarboxylase (AADC). This increases dopamine levels in your brain. Researchers at the University of Münster in Germany conducted a study with 40 healthy people. In this randomized double-blind study, they gave one group 100 mg of levodopa daily for 5 days. The other group took a placebo. 90 minutes later on each day, subjects were given a memory test based on vocabulary. The study found that levodopa significantly enhanced the speed, overall success, and long-term retention of novel words.401 2. L-DOPA promotes brain health. Research suggests Mucuna Pruriens protects your brain by regulating cognitive and neural functions. And even encouraging neural activity. Researchers in India showed that Mucuna Pruriens is a potent antioxidant. They performed assays to evaluate the enzymatic and nonenzymatic antioxidants in extracts. They found high levels of flavonoids, alkaloids, tannic acids, gallic acids, quercetin equivalents, and sitosterol equivalents.402 All of these compounds scavenge for free radicals in your brain. Free radicals are formed during normal brain activity, like the synthesis of ATP within your mitochondria. Your brain is equipped to eliminate some of these free radicals on its own. But especially in today’s environment in which we live, your brain is overwhelmed. Free radicals cause inflammation which damage and can kill brain cells. Affecting memory, learning, recall, cognition and mood. Mucuna Pruriens has been proven to be a very effective brain inflammation fighter. It even has the ability to chelate heavy metals like mercury and lead in brain cells. And it’s antibacterial.403 Mucuna Pruriens helps your brain make naturally occurring neuronal pigments called neuromelanins. They’re similar to the melanin found in your skin. And they’re often found in regions of your brain where dopamine is active. The synthesis of neuromelanins in the various regions of your brain is an important protective process. The melanic component is generated through the removal of reactive/toxic quinones that would otherwise cause neurotoxicity. This melanic component promoted by Mucuna Pruriens is what chelates and accumulates toxic, heavy metals like mercury and lead.404 How things go bad

As we get older, our brain chemistry and energy metabolism changes. ↓ Dopaminergic neurons are damaged or die ↓ Dopamine levels decline ↓ Stress levels increase ↓ Long-term memory and mood decline All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Parkinson’s Disease. L-DOPA benefits Mucuna Pruriens extract contains high levels of L-DOPA, the precursor to the crucial neurotransmitter dopamine. Dopamine is further synthesized into the neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline). Dopamine plays a critical role in learning and absorbing new information. Increasing brain levels of dopamine helps regulate mood and boost cognition. Research also suggests that Mucuna Pruriens provides antioxidants that defend against oxidative damage caused by free radicals.405 How does L-DOPA feel? Neurohackers report that using Mucuna Pruriens helps in multi-tasking, improving motivation, more focus, less stress, and a sense of calm. You could find your energy levels increase, less brain fog, and a boost in overall mood. A more positive outlook on life. And an increase in libido. The Research Mucuna Pruriens helps reduce stress A study was conducted to assess the role of Mucuna Pruriens in infertile men. It was done at King George’s Medical University in Lucknow, India. The study included 60 men who were undergoing infertility screening. And no surprise here; were found to be suffering from stress. The control group in this study were 60 age-matched men who had initiated at least one pregnancy. The infertile men were given 5 grams of Mucuna Pruriens seed powder per day for 3 months. Semen samples were collected at the beginning of the study. And after 3 months of treatment. The researchers found that treatment with Mucuna Pruriens significantly decreased stress levels. And increased sperm count to the same level as the fertile control group of men. They “concluded that M. pruriens not only reactivates the anti-oxidant defense system of infertile men but it also helps in the management of stress and improves semen quality.”406

L-DOPA improves learning This study in Germany was done with 40 healthy subjects. They were given 100 mg of L-DOPA or a placebo for 5 days in a randomized, double-blind trial. Subjects were trained on artificial vocabulary using a high-frequency, repetitive approach. This was done 90 minutes after L-DOPA administration on each day of the trial. The researchers found that L-DOPA significantly enhanced the speed, overall success, and long-term retention of the words.407 L-DOPA as an antidepressant Increasing dopamine in your brain also boosts your mood and libido. This study was done in India with mice. Researchers used the well-known Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test. The mice were fed Mucuna Pruriens seed extract, and then evaluated while performing, well… what mice do in the lab. The research team found that Mucuna Pruriens seed extract has significant antidepressant qualities. Which would simply verify what we already know in humans.408 Using Mucuna Pruriens extract is a great anti-depressant. Dosage Notes L-DOPA (Mucuna Pruriens 98% extract) suggested dosage for cognitive benefits is 250 – 500 mg per day. I recommend that you cycle the use of L-DOPA (Mucuna Pruriens). And use it only 4 or 5 days a week. This will help avoid tolerances and dependencies (which are common with any dopamine agonist). Side Effects L-DOPA is produced naturally in your body. So is considered well-tolerated and safe. And L-DOPA from Mucuna Pruriens extract is particularly well tolerated by most people. Research shows that the natural form of L-DOPA from Mucuna Pruriens compared to synthetic versions of L-DOPA provides similar results. But without the common side effects of nausea, vomiting, and involuntary muscle movement.409 But be very careful when working with dopamine. Too much and you can experience symptoms like hair loss, auditory or visual hallucinations, psychosis, Dyskinesia and more. Of course, if you begin to experience any of these side effects, stop supplementing with L-DOPA (Mucuna Pruriens) immediately. Like any natural supplement, it’s always better to find an organic source. Available Forms

Mucuna Pruriens is typically available in powder, capsule, or tablet form. Some are pure, dried Mucuna Pruriens powder. Several manufacturers offer Mucuna Pruriens extracts ranging from 15% - 98% L-DOPA. Or they tell you how many mg of L-DOPA is in each capsule or tablet. A few manufacturers call it “Velvet Bean Extract” with the percentage of L-DOPA in each capsule or tablet. It’s the same as Mucuna Pruriens. Try to find “organic” or “certified organic” if you can. And for Nootropic use, avoid synthetic L-DOPA which is typically used to treat Parkinson’s Disease. Nootropics Expert® Recommendation L-DOPA (Mucuna Pruriens) 250 - 500 mg per day I recommend using L-DOPA as a nootropic supplement. Your body does synthesize some L-DOPA on its own. And converts it into the essential neurotransmitters dopamine, epinephrine, and norepinephrine. But as you get older, dopamine receptors die. Or your body doesn’t convert the necessary amino acids well enough to supply the neurotransmitters you need for an optimized brain. L-DOPA is helpful to boost energy levels, clear brain fog, improve mood and libido. L-DOPA is especially helpful for those suffering from neurodegenerative diseases like Parkinson’s. And the natural form of L-DOPA from Mucuna Pruriens often offers better results with fewer side effects than prescription drugs. I suggest starting with a dose of 100 - 250 mg daily for nootropic use. You may want to cycle L-DOPA. Use it for 4 or 5 days and take a break unless you are treating something specific like Parkinson’s. Tolerance can be a problem when working with dopamine. As is dependence or addiction.

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Lemon Balm Lemon Balm is known for its anti-anxiety and calming effects, improving focus, memory and cognition, and reducing irritability and depression Lemon Balm (Melissa officinalis) is an herb that’s native the Mediterranean region. And now found in gardens throughout Europe and North America. Lemon balm has a long history as a treatment for stress, anxiety, thyroid issues, indigestion, infections, viruses, and inflammation. Related to the mint family of herbs, lemon balm has a subtle lemon scent. And its small white flowers attract bees. Hence the botanical name ‘Melissa’, which is Greek for honey bee. The first recorded medical use of lemon balm dates back to Dioscorides, the ancient Greek physician, who used the herb for its anti-bacterial and soothing properties. The famous Swiss Renaissance physician, Paracelsus, called it the “elixir of life”. In the 16th century, English botanist John Gerard, gave it to his students to “quicken the senses”. This appears to be the first recorded use of the herb for brain and cognitive health. The most recent research shows lemon balm has remarkable healing and regenerative effects on your brain. It stimulates memory, and supports the health of your brain’s white matter. Lemon balm’s two primary compounds that affect brain health are eugenol and rosmarinic acid.410 Eugenol is an antioxidant 5-times more potent than alpha-tocopherol found in Vitamin E. So lemon balm acts to boost your body’s natural healing processes by eliminating free radicals that damage brain cells. And lemon balm helps increase levels of your body’s most powerful built-in antioxidants, dismutase and glutathione peroxidase.411 Rosmarinic acid promotes an anti-depressant effect in your brain by downregulating mitogen-activated protein kinase phosphatase-1 (Mkp-1). And it upregulates brain-derived neurotrophic factor (BDNF), along with boosting dopamine synthesis.412 How does Lemon Balm work in the Brain? Lemon Balm boosts brain health and function in several ways. But two in particular stand out. 1. Lemon Balm boosts memory. Lemon balm increases the activity of the neurotransmitter acetylcholine (ACh) in your brain. When your brain sends signals, it uses acetylcholine to keep the signals moving. But once used, your brain removes acetylcholine with an enzyme called acetylcholinesterase (AChE).413 But if you have too much AChE, as is the case with Alzheimer’s patients, it restricts brain signaling.

One way to prevent this signal failure is to prevent the breakdown of acetylcholine. The compound rosmarinic acid in lemon balm encourages blood flow, which helps to keep brain cells from dying.414 And it inhibits the formation of AChE. The result is that your brain is stimulated, memories continue to form, and brain fog is eliminated. 2. Lemon Balm reduces stress. One-way lemon balm does this is to promote GABA, a glutamate inhibitor in your brain. Glutamate excites brain cells to act. While this excitation is necessary, too much glutamate results in cell death. Lemon balm promotes a better balance in glutamate levels and helps new cell growth.415 The result is a boost in memory and reduction in stress. Largely due to eugenol, one of the components of lemon balm. How things go bad Chronic stress, anxiety, poor blood flow and free radicals (oxidation) can damage your brain. And one of the ways this manifests is memory loss. It comes as no surprise that people with memory loss experience higher rates of anxiety and depression. As verified in one Australian research study.416 ↓ Chronic stress reduces memory capacity ↓ Toxins kill brain cells from the inside ↓ Free radicals destroy neurons and synapses ↓ Acetylcholine (ACh) levels decline ↓ Brain-derived neurotrophic factor (BDNF) declines Under conditions of chronic stress your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition, and decision-making all suffer as a result. Lemon Balm benefits Lemon Balm undoes damage to the brain caused by chronic stress and oxidative damage. It boosts GABA levels and keeps toxic glutamate overload in check. Lemon balm inhibits the enzyme AChE that breaks down acetylcholine (ACh) levels in your brain. Boosting ACh improves memory, recall and cognition. Rosmarinic acid in lemon balm works as an antidepressant. And boosts brain-derived neurotrophic factor (BDNF) which promotes the growth, maturation and maintenance of brain cells. And the eugenol in lemon balm is a very powerful antioxidant. Eliminating oxidative damage in brain cells by neutralizing free radicals. And boosting your brain’s own antioxidants to provide even more protection.

How does Lemon Balm feel? The effects of supplementing with Lemon Balm (Melissa officinalis) can provide an anti-anxiety effect within minutes of taking it. Some users say it works as well as popping a Xanax. You should experience an increase in focus along with a sense of calm. And even though lemon balm works well as a sleep aid, taking it during the day shouldn’t make you drowsy. Users report lemon balm effective in taming racing thoughts that come with Obsessive Compulsive Disorder (OCD). Some even use lemon balm as an effective way to control irritable bowel syndrome. The Research Research continues in medicinal plants and herbs that have been used for millennia to treat cognition and memory problems. One study conducted at the University of Newcastle upon Tyne in the UK, found Melissa officinalis to be one of the strongest in its effects on acetylcholine receptors. And being an effective aid for memory.417 Lemon Balm as a Nootropic Lemon Balm has been shown to improve problem-solving and memory in both human and animal models. And age seems to make no difference. All groups using lemon balm showed better recall and problem-solving. Some recent studies with Alzheimer’s patients have shown improvement when using lemon balm. In one study done in China, researchers gave Sprague Dawley rats eugenol. One of the active compounds found in lemon balm, eugenol is a potent antioxidant. In this case it helped test subjects get their memory back.418 Another study noted that lemon balm inhibits acetylcholinesterase (AChE). This enzyme breaks down the critical neurotransmitter acetylcholine (ACh). ACh is crucial to creating memories and cognition. Lemon balm was shown to boost and support mood and memory.419 Lemon Balm for Stress Reduction A double-blind, placebo-controlled experiment was conducted in the UK with 18 healthy volunteers. The subjects received two separate single doses of standardized lemon balm extract (300 mg and 600 mg), or a placebo, on separate days. Followed by a 7-day washout period. Mood was assessed before dosing, and 1-hour after dosing with lemon balm extract. The study subjects did a 20-minute version of the Defined Intensity Stressor Simulation (DISS) battery of tests. The results showed that a 600 mg dose of lemon balm eliminated the negative mood effects of doing the DISS tests. They reported an increase in calmness and reduced alertness. The researchers also reported a significant increase in mathematical processing, with no reduction in accuracy. This was after taking the lower 300 mg dose.

The nootropic benefits of lemon balm, according to this test, was a boost in cognition, and had a calming effect.420 Dosage Notes Lemon balm has a long history of use in treating a host of ailments. Including memory and cognition, gas, bloating, earache, vomiting, headache, toothache and insomnia. For nootropic use, Melissa officinalis (lemon balm) comes in tea and capsule form. For the most potent dosage, find lemon balm extract in capsules. The suggested dose by most naturopaths and alternative health doctors is 300 mg of lemon balm extract 2-3 times per day. Dosage of lemon balm leaf as a tea is 1 – 2 grams per cup of tea. You can use lemon balm in the morning to address daytime anxiety. And towards evening to support relaxation and sleep. Side Effects Lemon balm is considered non-toxic and very safe for most users. Most neurohackers won’t experience any side effects. Note: Lemon balm may have an “antithyrotropic effect”. So if you’re hypothyroid, and on thyroid medication, you may want to avoid using lemon balm. And use caution when combining lemon balm with; anti-anxiety meds, anti-histamines, muscle relaxers, anti-seizure drugs or tranquilizers. Available Forms For nootropic use, lemon balm supplements are available as loose-leaf tea, tinctures, and capsules. Most neurohackers use lemon balm capsules which come as ground leaves, or an extract. The lowest active dose is 300 mg of standard lemon balm. Supplementing above this dose seems to offer dose-dependent benefits. In other words, you’ll get more benefit by taking higher doses. (i.e. 300 mg lemon balm 2-times per day). Nootropics Expert® Recommendation Lemon Balm extract 300 - 600 mg per day I recommend using Lemon Balm as a nootropic supplement. Your body does not make Lemon Balm on its own. So you must take it as a supplement. Lemon Balm is especially helpful for those suffering from anxiety and stress. Studies show it helps stop and reverse the devastating effects of anxiety and stress on your brain, and body. This nootropic helps repair damage to brain cells caused by chronic stress and anxiety.

Lemon balm is reported to work well for those dealing with Obsessive Compulsive Disorder (OCD). Taming racing thoughts, and helpful in dealing with stressful situations. Lemon balm is also helpful for those suffering from Alzheimer’s. It has been shown to help reduce agitation and improve symptoms of mild to moderate Alzheimer’s disease. It may also be of benefit in relieving some symptoms of ADHD. You can safely take up to 900 mg of Lemon Balm (Melissa officinalis) extract daily if needed. One dose first thing in the morning. One dose early afternoon. And the last dose in the evening. And for memory, lemon balm is great to stack with CDP Choline and Acetyl L-carnitine.

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L-Glutamine L-glutamine can help improve alertness, concentration, focus, memory and mood, boost Human Growth Hormone and reduce anxiety L-glutamine is a conditionally essential amino acid and main precursor for the production of the neurotransmitters glutamate and GABA (γ-aminobutyric acid) in your brain. L-glutamine supplementation is mostly talked about in athletic and body building circles for its effect on human growth hormone and muscle recovery after a workout. But L-glutamine is largely ignored by the nootropics community. L-glutamine is so critically important to the optimized brain that by reading this chapter, you’ll understand why it may be an important addition to your nootropic stack. As an ‘excitatory’ neurotransmitter, glutamate is released from pre-synaptic cells and then binds to postsynaptic cells inducing activation. Too much glutamate and neurons become overactive causing a toxic environment that is harmful to neurons. And to cognition. To keep this process in check, glutamate is also a precursor to the ‘inhibitory’ neurotransmitter GABA. GABA works by preventing neural signaling in over-excited neurons caused by glutamate that could result in anxiety and depression.421 The balance of glutamine and glutamate has been identified in an array of brain conditions (i.e. mental illness, tumor, neurodegeneration) as well as in normal brain function.422 The precursor relationship between glutamine and glutamate/GABA is often referred to in scientific and research circles as the Gln/Gly(GABA) cycle.423 Glutamine is naturally synthesized from glutamate and ammonia in brain cells called astrocytes in a reaction catalyzed by glutamine synthetase (GS). Newly synthesized glutamine is transferred to neurons and hydrolyzed by phosphate-activated glutaminase (PAG) to then produce glutamate. A portion of which may be decarboxylated to GABA or transaminated to Aspartate. Glutamate, the excitatory neurotransmitter, and GABA, the calming neurotransmitter rely on this cycle to maintain homeostasis within your brain. Glutamine also modulates the synthesis of Nitric Oxide by controlling the supply of its precursor arginine. When this cycle gets out of whack, things start to break down. The results can be particularly nasty. And result in conditions like epilepsy, or hepatic encephalopathy which effects behavior, mood, speech, sleep and the way you move. L-glutamine becomes a “conditionally” essential amino acid when your body can’t produce enough on its own. And you need to replenish L-glutamine levels either through supplementation or food.424 L-glutamine can be found in foods such as beef, pork, fish, eggs, milk and dairy products, wheat, cabbage, beets, beans, spinach and parsley.

How does L-glutamine work in the Brain? L-glutamine helps brain health and function in several ways. But two in particular stand out. 1. L-glutamine is critical for an optimized brain. L-glutamine is a precursor to the neurotransmitter glutamate in your brain. The balance of glutamine and glutamate is crucial to an optimized and healthy brain. The normal cycling of glutamine and glutamate takes a huge amount of energy in the brain. Research has estimated that the Gln/Gly(GABA) cycle accounts for more than 80% of cerebral glucose consumption.425 So when you’re using nootropics like Resveratrol or PQQ to boost mental energy, much of that energy is going towards maintaining this Gln/Gly(GABA) cycle. A disruption of this cycle results in all kinds of problems including Reye’s Syndrome, epilepsy, bipolar disorder, schizophrenia, anxiety, depression, and alcohol addiction.426 One Korean study measured Glutamate and Glutamine concentrations in the prefrontal cortex of mice infused with an astrocyte toxin. And they used other inhibitors to disrupt the Glu/Gln cycle. Glutamate and glutamine levels decreased on the 5th day in the mice. The animals experienced immobility and a decreased preference for sucrose (sugar). A sure indication in mice of depression. Direct infusion of L-glutamine completely reversed all the impairments that were originally induced in the animals. And the researchers concluded that neuronal deficiency of L-glutamine causes depression.427 2. L-glutamine also helps prevent brain aging. Researchers have long been on the hunt to determine what causes the human brain to age. Recently, mitochondrial dysfunction has been implicated in the loss of brain function in neurodegenerative diseases and aging.428 Leading to an abnormal increase in the excitatory neurotransmitter glutamate. A study at the New York University School of Medicine used 28 patients with mild traumatic brain injury and 22 matched controls. Gray and white matter in their brains was measured using MRI’s. The study found that one year after traumatic brain injury there was significant global brain atrophy. Much larger than in the control subjects. The team noted the amount of brain damage from just one concussion. And that this type of injury was not exclusive to a severe blow to the head. Even mild injury could cause brain damage.429 Most of the damage was associated with a disrupted Glu/Gln cycle and an abnormal increase in glutamate levels.430 How things go bad Low levels of L-glutamine are associated with a variety of health problems. ↓ Cellular energy drops and immune system weakens ↓ Short- and long-term memory declines

↓ Anxiety, insomnia and lack of concentration ↑ Muscle spasms, hypertension, convulsion, Tourette’s Syndrome and epilepsy ↑ Ammonia levels rise in brain cells431 ↓Poor digestion, bloating, flatulence, and constipation When your neurotransmitters, including L-glutamine and glutamate are in balance, you feel motivated, productive, and energetic. And you feel calm and relaxed during downtime. When L-glutamine levels are low you feel filled with dread, you’re constantly worried, you have racing thoughts, and you’re frequently late and disorganized. Many people in this L-glutamine -slump resort to high carbohydrate foods, and drugs or alcohol to relax. L-glutamine benefits The amino acid L-glutamine is the precursor to L-glutamate production in your body. L-glutamate gets converted to GABA. Glutamate is your body’s most abundant excitatory neurotransmitter. Which is responsible for attention span, brain energy, learning ability, memory, and staying awake. An enzyme called glutamate decarboxylase converts glutamate to GABA. It does it with the help of the active form of Vitamin B6 (Pyridoxal-5-Phosphate (P5P)). The amino acid taurine helps increase the communication and productivity of this enzyme. And zinc helps the release of GABA from its receptors. When this Gln/Gly(GABA) cycle works efficiently, you feel relaxed with no stress or feelings of anxiety. Detoxification of your liver results in a more restful night’s sleep. Focus, concentration, memory and mood all improve. How does L-glutamine feel? During times of chronic, long-term stress caused by physical exertion or illness, glutamine levels in your body can drop by 50% or more.432 Supplementing with L-glutamine can improve your quality of life, increase energy levels, reduce muscle aches, improve digestion, and gut health, improve quality of sleep, and reduce pain and fatigue. When you balance L-glutamine levels in your brain, you feel relaxed and calm. Cravings for sugar and alcohol will decline. L-glutamine will help in recovery from workouts and improve performance. You may find it easier to lose weight. Many neurohackers use L-glutamine to help heal Leaky Gut Syndrome and reduce the symptoms of

Crohn’s and Celiac Disease. As a nootropic, L-glutamine can help improve alertness, concentration, focus, memory and mood. The Research L-glutamine was identified as a neurotransmitter several decades ago. And there has been a lot of research on L-glutamine published since. But most of it is focused on strength training and maintaining muscle mass in athletes. And for people healing from surgery or recovering from illness. But L-glutamine can be a powerful nootropic as well. Here are a couple of studies looking at Lglutamine for brain health. L-glutamine Increases Human Growth Hormone Bodybuilders and athletes use supplementary L-glutamine to help repair and build muscle. And there are several studies supporting the notion that L-glutamine increases Human Growth Hormone. In one study, researchers worked with 9 healthy subjects and gave them 2 grams of L-glutamine in a cola drink. Blood samples were taken before drinking the cola-spiked drink, then again at 30 mins., 60 and 90 mins. The researchers found that both blood L-glutamine and human growth hormone levels were significantly higher than before taking L-glutamine. The team concluded that “a surprisingly small oral L-glutamine load was capable of elevating growth hormone”.433 Human growth hormone and Brain-Derived Neurotrophic Factor (BDNF) are intricately linked. BDNF is involved in Long-Term Potentiation and the encoding of long-term memories. L-glutamine Improves Cerebral Performance Lack of concentration and poor memory can be improved by supplementing with L-glutamine and Vitamin B3 (niacin). Some of the glutamine in your blood is transformed into glutamic acid in your brain. Glutamic acid functions first as fuel, but it also gets rid of excess ammonia by binding to this cellular toxin and converting it into glutamine. A study in the Netherlands conducted a randomized, double-blind, placebo controlled trial with 42 healthy men and woman aged 40 – 76 years. Subjects received a 5-gram stack containing glycine, Lglutamine and niacin twice daily for 3 weeks. The L-glutamine stack increased Human Growth Hormone a whopping 70% compared to placebo. But surprisingly it wasn’t the growth hormone that improved memory and vigor. It was insulin-like growth factor-I that improved memory and vigor. Attributed to the L-Glutamine stack the subjects took for 3 weeks.434 Dosage Notes

Most people don’t get enough L-glutamine from food alone. And why adding L-glutamine to your nootropic stack can boost your immune system, improve your ability to fight infection and diseases, and boost cognition. The recommended daily dosage of L-glutamine is 2 to 5 grams per day. Serious power athletes often dose up to 10 grams of L-glutamine per day. Side Effects L-glutamine is considered very safe when taken in normal recommended doses. Rarely do people report side effects like nausea, vomiting, flatulence, abdominal pain, constipation, dry mouth, hemorrhoids, dizziness, depression, skin rashes, insomnia and increased sweating. Remember, the balance between L-glutamine and glutamate (Gln/Gly(GABA) cycle) is critical for optimal health. Some recent research has shown that L-glutamine can stimulate tumor growth. So if you are dealing with any form of cancer you should not use L-glutamine. If you are dealing with cirrhosis of the liver, you should avoid L-glutamine. If you have severe liver disease that includes difficulty thinking or confusion (hepatic encephalopathy), don’t use L-glutamine. If you are allergic or sensitive to Monosodium glutamate (MSG), you may be sensitive to L-glutamine because your body converts it to glutamate. And if you have a severe mental disorder including mania or frequently have seizures you may want to avoid L-glutamine. Available Forms L-glutamine as a supplement is available in tablets, capsules and powder. The most commonly available form of L-glutamine as a nootropic supplement is called “free form” glutamine. Trans-Alanyl or Alanyl-L-glutamine is an amino acid attached to another amino acid which aids in digestion of this supplement. If you are using it to boost athletic performance and speed recovery, both forms of L-glutamine are best taken right before or after a workout. Using it with small meals before or after your workout session can help support your metabolism and weight loss goals. And will assist in muscle building, recovery and maintenance. Nootropics Expert® Recommendation L-glutamine 2 – 5 grams per day. I recommend using L-glutamine as a nootropic supplement if you’re dealing with anxiety or stress. And to calm or keep in check some of the stimulatory effects of some nootropics.

Your body does make L-glutamine on its own from glutamate in your brain. But most people do not maintain an adequate supply of L-glutamine in their system. And if you’re dealing with illness, recovery from surgery, strenuous physical activity like working out, Leaky Gut Syndrome, Crohn’s, or Celiac Disease, and need some help in recovery, L-glutamine can help. L-glutamine also helps to curb the desire for sugar, carbs, and alcohol. I suggest first trying a L-glutamine supplement at a dose of 500 mg. And see how you react. You can safely dose up to 20 grams of L-glutamine per day. But most neurohackers find much lower doses effective for boosting cognition, mood and memory.

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Lion’s Mane Lion’s Mane Mushroom is known for stimulating Nerve Growth Factor, improving cognition and memory, and relieving depression Lion’s Mane (Hericium erinaceus) is a medicinal mushroom proven to benefit the brain, nerves, and immune system. Unlike other mushrooms sporting a cap and stem, Lion’s Mane has long, flowing, white tendrils. Resembling a Lion’s Mane. Other names include Monkey’s Head, Bearded Tooth, Pom Pom Blanc, Hedgehog Mushroom and Satyr’s Beard. This parasitic fungus grows hanging off logs and trees. And is native to North American, Europe and Southeast Asia. In Japan, it’s called yamabushitake or “those who sleep in mountains”. Referring to the Shugendo sect of hermit monks and their long, flowing robes. Known for its powerful effects as a “brain tonic”, Lion’s Mane is said to have been used as a tea for thousands of years by Buddhist monks. To enhance brain power and heighten their ability to focus during meditation. As a nootropic, Lion’s Mane has been shown to be particularly effective in stimulating Nerve Growth Factor (NGF) in the brain. NGF is produced in the hippocampus throughout life. Modulating cholinergic receptors and neuroplasticity.435 And is essential for learning. Nerve Growth Factor are special proteins that function to regenerate neurons. Lion’s Mane contains two unique classes of NGF’s – hericenones and erinacines which easily cross the blood-brain barrier. Lion’s Mane, like other medicinal mushrooms, contain high amounts of the antioxidant beta-glucoxylan and four other polysaccharides and polypeptides. Having a significant impact on enhancing your immune system. And decreasing tumor growth. Lion’s Mane has also been studied in reducing amyloid plaques. These clumps of beta-amyloid proteins block signals between neurons. And are implicated in Alzheimer’s and other neurodegenerative diseases. Lions’ Mane is also used to treat Lyme’s Disease, and digestive tract issues. Here we’re talking about Lion’s Mane Mushroom and its effects on brain health and chemistry. How does Lion’s Mane Work in the Brain? Lion’s Mane boosts brain health and function in several ways. But two in particular stand out. 1. Lion’s Mane Mushroom stimulates the synthesis of Nerve Growth Factor (NGF). NGF is a protein that plays a major role in the maintenance, survival, and regeneration of neurons.

NGF is required by your brain to keep neurons strong and healthy. When various neurological disorders occur, your brain is unable to produce its own internal source of NGF. In a study done in Kuala Lumpur in 2013, scientists showed that Lion’s Mane extract induced NGF synthesis and promoted neurite outgrowth.436 2. Lion’s Mane is effective in reducing anxiety and depression. Some even call it the “smart mushroom” for its ability to improve cognition, memory and work as an anti-depressant. A study by researchers in Japan worked with 30 women. The female subjects had been complaining about menopause, depression, sleep quality and other issues. The women randomly received Lion’s Mane-laced cookies or a placebo for 4 weeks. The researchers found that Lion’s Mane “has the possibility to reduce depression and anxiety, and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus”.437 How things go bad Science once believed that the brain could not grow new brain cells. That once our brain developed during childhood, and we reached adulthood, we had all the brain cells we’d ever have. Now we know that neurons can regenerate. But that doesn’t mean they will regenerate. A number of health issues can contribute to neurodegeneration. ↓ Decrease in Nerve Growth Factor = Decrease in Long-Term Potentiation affecting long-term memory438 ↓ Brain cells die and are not replaced ↓ Neuroplasticity declines resulting in poor memory ↓ Neurotransmitters decline resulting in anxiety, poor mood and depression All of these age-related changes are contributing factors to neurodegenerative diseases like Alzheimer’s, Parkinson’s and others. And anxiety, depression and mood disorders affect quality of life. Lion’s Mane benefits At least a dozen peer-reviewed studies have been published on Lion’s Mane benefits to brain health since 1991. Dr. Kawagishi of Japan was first to identify the Nerve Growth Factor properties of Lion’s Mane Mushroom.439 In one double-blind, placebo-controlled trial, researchers in Japan worked with 50 – 80 year men and women. All suffered from mild cognitive impairment. The trial subjects received four 250 mg tablets containing 96% of Yamabushitake (Lion’s Mane) dry powder three times a day for 16 weeks. The men and women were tested at 4, 8, 12 and 16 weeks. At each of the testing periods, the subjects who had used Lion’s Mane showed a significant

improvement in cognitive scores. And their scores were increasing while on Lion’s Mane supplementation. But 4 weeks after stopping Lion’s mane supplementation, their cognitive scores decreased significantly. The researchers concluded that Lion’s Mane Mushroom is effective in improving mild cognitive impairment.440 How does Lion’s Mane feel? You may not experience the effects of supplementing with Lion’s Mane Mushroom immediately. But many users report with continued use of Lion’s Mane, a boost in mood and mental energy. Some report it increases depth perception. And an improvement in sense of smell. Others testify to improved decision-making, the ability to solve problems and learning. Likely due to Lion’s Mane ability to improve neuroplasticity. The overall consensus is Lion’s Mane Mushroom’s ability to lessen anxiety, reduce depression, and improve concentration. The Research Lion’s Mane Mushroom has been used as a food and herbal medicine since ancient times in East Asia. And it has been reported in scientific research that Lion’s Mane promotes Nerve Growth Factor both in the petri dish as well as in animal and human test subjects. Lion’s Mane Prevents Cognitive Dysfunction In this study, researchers examined the effects of Lion’s Mane on amyloid β(25-35) peptide-induced learning and memory deficits in mice. Amyloid β(25-35) peptide is implicated in diseases like Alzheimer’s. Mice were injected with the peptide on days 7 and 14 of the trial. And they were fed a diet containing Lion’s Mane over 23-days of the experiment. The results showed that Lion’s Mane prevented short-term and visual recognition memory induced by amyloid β(25-35) peptide. They concluded that Lion’s Mane Mushroom “may be useful in the prevention of cognitive dysfunction”.441 Lion’s Mane Induces Nerve Growth Factor In this trial, mice were fed Lion’s Mane 5% freeze-dried powdered extract for 7 days. Researchers found an increase in the level of Nerve Growth Factor (NGF) in the hippocampus of the mice. Concluding that Lion’s Mane “contains active compounds that stimulate NGF synthesis”.442 Lion’s Mane Repairs Nerves This study done with rats, Lion’s Mane extract was able to promote neuron regrowth after injury. Rats with gluteal nerve damage were able to walk again after consuming water containing Lion’s Mane extract.

The researchers concluded that Lion’s Mane regenerates damaged nerve cells. In this case, the reversal was so profound, the rats went from being totally disabled to walking again.443 Dosage Notes Dosing of Lion’s Mane Mushroom depends on the strength of the extract. It’s available in capsule or powder form. For Lion’s Mane 10:1 extract (30% polysaccharide), daily dosage is 500 – 1,000 mg taken 1 to 3 times per day. Other retail extract dosages of Lion’s Mane ranges from 300 mg to 3000 mg dosed 1 – 3 times per day. Check the label and see what the manufacturer recommends. And when first using the supplement, start with the lowest dose and see how your body reacts. Side Effects Lion’s Mane Mushroom is non-toxic and considered very safe. So there are very few side effects reported. Some neurohackers report itchy skin from higher doses. Likely attributable to a boost in Nerve Growth Factor. Lion’s Mane has been tested in animals showing no side effects or toxicity even up to 5 grams per kilogram. Available Forms Lion’s Mane Mushroom (Hericium erinaceus) as a supplement is usually offered as an extract. In powdered form, or in a capsule. Supplement makers of nootropic stacks sometime include Lion’s Mane as well. For example, Mind Lab Pro® includes 500 mg of the full fruit extract in their formula. Each formula will be different depending on synergy with the stack, and type of extract used. When choosing a Lion’s Mane supplement, there’s debate over the best form of extraction to achieve the mushroom’s full medicinal benefit. Some say your best option is a hot water extraction. Another says alcohol extraction. Another claims both are necessary. But when it comes to mushrooms, saying that one is “more potent” than another is just too simplified to be true. This is as much an art as it is science. Much more important is choosing a supplement that includes the mycelium of Lions Mane Mushroom. In this mushroom, the fruiting body does not contain erinacines which is the compound that boosts Nerve Growth Factor (NGF). The nootropic benefits of hericenones only found in the fruiting body or top of the mushroom help support your immune system and get rid of Amyloid β(25-35) peptide implicated in diseases like

Alzheimer’s. The challenge is getting a Lions Mane Mushroom extract that contains the full spectrum found in both the mycelium and fruiting body. But the mushroom must be grown in liquid and not a solid substrate like grain. Otherwise you’ll get ground up grain without the important erinacines needed for increased NGF. Look at the manufacturers literature and marketing material and find out how their Lions Mane is grown. And read the reviews on shopping sites as well as forums. Types of Lion’s Mane available: • • •

• •

Plain Lion’s Mane: Pure, powdered mushroom. Often freeze-dried, and the cheapest form available. Can be added to water, juice or smoothies. Lion’s Mane Extracts: A more potent form of mushroom. Often presented as 14:1 or 10:1 extracts (14 pounds or 10 pounds reduced to 1 pound of extract). Standardized Lion’s Mane: Processed to provide exact levels of active ingredients. You can get Lion’s Mane standardized to 30% and 50% polysaccharides (the active hericenones and erinacines are metabolites of polysaccharides). Lion’s Mane tea: Since this is a popular mushroom in the kitchen, the taste is acceptable. But it’s hard to get a handle on how much actual active ingredient you’re getting. Amycenone®/PLM-Fraction: This “branded” product is standardized to Hericenones 0.5%, Amyloban 6%. It seems to target a lesser-known Lion’s Mane active ingredient–Amyloban– which is positioned as a mushroom compound that fights beta-amyloid proteins. Originating in Japan, it is extremely expensive, and may be found in a supplement called Amyloban®3399.

And if you decide to pick your own, before consuming any wild mushroom, make sure that it is accurately identified. Mushroom poisoning is a real problem if you pick the wrong one. For a full list of Mycology societies that may be able to help you, go to the North American Mycological Association website (www.namyco.org). Nootropics Expert® Recommendation Lion’s Mane 300 to 3,000 mg per day I recommend using Lion’s Mane as a nootropic supplement. Your body does not make Lion’s Mane on its own. So you need to take it as a supplement. Lion’s Mane is especially helpful for regenerating brain cells. It prevents neurodegenerative diseases like Alzheimer’s and Parkinson’s. And it boosts long-term potentiation for memory and mental sharpness. By stimulating Nerve Growth Factor. Lion’s Mane also helps boost mood, tame anxiety and relieve depression. For a better quality of life.

I suggest starting with a dose of 500 mg daily. The best human study used 750 mg per day. But another researcher found lower concentrations may stimulate NGF better than higher concentrations.444 Start at 500 mg per day and see how it works for you. If you don’t experience a benefit, boost Lion’s Mane in small increments of 250 mg per day until you notice an improvement. Lion’s Mane is a great compliment to a nootropic stack including Aniracetam, Alpha GPC, ALCAR, and Omega-3’s for an immediate cognitive boost.

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L-Theanine L-Theanine is known for boosting alpha and theta brain waves, anti-anxiety, boosting cognition, improving memory, and better-quality sleep L-Theanine (r-glutamylethylamide) is a non-dietary amino acid found in tea. And especially high levels in green tea (camellia sinensis). L-Theanine was first isolated from green tea in Japan by Sakato in 1949. As an analogue of glutamate and glutamine, it’s hydrolyzed in your intestine and liver into l-glutamate and ethylamine. And easily crosses your blood-brain barrier. L-Theanine is one of the very few nootropics known to modulate brain waves. It affects alpha brain waves which are associated with relaxation. Providing an alert calmness, L-Theanine helps in promoting super-learning, flow states and joy. L-Theanine boosts the neurotransmitters serotonin, dopamine and GABA in your brain. As well as increasing Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF).445 L-Theanine is known for helping to relieve stress, improve cognition, boost mood and cognitive function. How does L-Theanine Work in the Brain? L-Theanine boosts brain health and function in several ways. But two in particular stand out. 1. L-Theanine reduces physical and mental stress. L- Theanine helps increase alpha brain waves which are associated with mental relaxation and concentration. One study in South Korea worked with 20 healthy male volunteers aged 18 – 30 years. One group was given L-Theanine tablets, and the other group a placebo daily for 7 days. Brain waves were measured 40 minutes after administration of the tablets. The researchers analyzed alpha wave power values. And concluded that L-Theanine tablets promoted the release of alpha brain waves related to mental relaxation and concentration.446 In May 2016, researchers at Simon Fraser University in Canada developed a technology to clinically measure brain wave patterns. With this technology, we’re now able to detect cognitive dysfunction before it happens. Imagine the implications of this new technology when applied to the nootropics world.447 2. L-Theanine increases neurotransmitters. Research shows that L-Theanine increases dopamine, serotonin, and GABA in your brain.448 And it reduces the excitatory neurotransmitter glutamate which is associated with stress, tension and agitation.449 A study done in Japan worked with 12 people who underwent 4 separate trials. One in which they took L-Theanine at the start of the experiment. One in which they took it half-way through. And two control

trials in which they took either a placebo or nothing. The results showed that L-Theanine resulted in a reduction in heart rate and s-IgA associated with acute stress. The researchers concluded that L-Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation.450 How things go bad: As we get older, our brain chemistry and energy metabolism changes. ↓ Neurotransmitter levels decline ↓ Glutamate levels increase ↓ Stress levels increase ↓ Long-term memory and mood decline ↓ Quality of sleep declines All of these changes can happen at any age once we reach adulthood. And are contributing factors to the neurodegenerative diseases of aging, and quality of life. L-Theanine benefits L-Theanine energizes without draining, calms without putting you to sleep, and motivates without causing a jagged edge. Tea (as a source of L-Theanine) can have as much caffeine as some coffees. And yet doesn’t exert the same “speedy” effect. And the reason is the ingredient L-Theanine. You can actually see L-Theanine’s effect in your brain using an EEG. Brain waves are smoothed out rather than flattened out.451 So your body is relaxed, your mind is calmed, but you don’t get sleepy. And L-Theanine, once it crosses the blood-brain barrier, raises levels of serotonin and dopamine.452 L-Theanine even improves your quality of sleep. Researchers in Japan gave volunteers 200 mg of LTheanine daily and recorded their sleep patterns. Sleep quality, recovery from exhaustion, and feeling refreshed were all enhanced by L-Theanine.453 And L-Theanine puts you in a better mood. Once it crosses your blood-brain barrier, L-Theanine changes levels of amino acids affecting serotonin, dopamine, and GABA. Having a modulating effect on mood.454 How does L-Theanine feel? Your unique neurochemistry including neurotransmitters, brain waves, brain structure and even regional brain activity will influence your response to L-Theanine. Most neurohackers report a calming effect within 30 – 45 minutes of taking L-Theanine. Cognition gets a boost, and energy levels rise without the jitteriness caused by stimulants like caffeine.

Some report L-Theanine has stopped their anxiety and panic attacks. Just don’t combine it with antianxiety meds like Xanax. Most report an overall improvement in the sense of well-being and quality of life. And nearly all remark on better quality sleep. The Research Green Tea reduces incidence of stroke Research has found that if L-Theanine is present in the body at the time stroke occurs, brain damage will be significantly reduced. In this monster study done in China, researchers selected 14,212 subjects from 12 provinces. Ages ranged from 35 – 60 years old. The study looked at tea drinking status, dose, and type of teas. This study concluded there was a 40% decreased risk of stroke in those who drank green, black, or jasmine teas.455 L-Theanine improves memory In this double-blind, placebo-controlled study, the effect of L-Theanine on memory and attention was investigated. 91 subjects with mild cognitive impairment were enrolled in this study. One group received 1,680 mg of L-Theanine daily for 16 weeks. And the control group received a placebo. The study concluded that L-Theanine increased brain Theta waves associated with cognitive alertness and creativity. And there were improvements in memory. The results of this study suggested that LTheanine has potential as an intervention for cognitive improvement.456 And that is an understatement by any stretch. People spend years meditating. With the goal of reaching consistent access to brain wave states like Theta. In this trial, they did it with a dose of L-Theanine. The same type of dose you could get with a few cups of quality green tea. L-Theanine reduces stress Considerable research has been dedicated to L-Theanine and its benefits to stress reduction in both animal and human studies. And we have ample documentation that corticosterone and stress exert negative effects on memory.457 Corticosteroids which are secreted after stress, have a profound impact on long-term potentiation and memory formation.458 In this animal study, rats were fed water containing L-Theanine for 3 weeks and put through some stress inducing exercise. The researchers found that corticosterone levels were lower in the rats who used LTheanine compared to those who had none. In fact, stress had no effect on the animals who were fed L-Theanine. Memory was not affected. The researchers concluded that L-Theanine modified corticosterone secretion. And L-Theanine is a strong

preventive measure in preventing memory loss otherwise induced by stress.459 Dosage Notes Recommended dosage of L-Theanine is 200 – 400 mg once or twice per day. With a maximum of 1,200 mg per day according to the Cleveland Clinic.460 L-Theanine is water soluble so you can take it with water. Labels on quality green tea often only display the amount of green tea leaf available in each bag in milligrams (mg). But not it’s L-Theanine content. Green tea that’s steeped correctly will offer 1-2% LTheanine per cup. So 1,500 mg of green tea leaf would be about 30 mg. of L-Theanine (at 2%). We often say that YMMV, and this is especially applicable to L-Theanine. Find out what works best for you. Start at a lower dose like 100 mg. And work your way up until you achieve the effects you’re looking for. Side Effects L-Theanine is a naturally occurring amino acid found in plants like tea or one species of mushroom. So it’s considered non-toxic and very safe. Theanine seems to decrease blood pressure. So if you’re on meds for high blood pressure, use LTheanine with caution. Your blood pressure could go too low. Available Forms L-Theanine is available in green, black, and white teas. Green tea contains the most L-Theanine. A great side benefit for neurohackers is green tea also contains caffeine. A cup of good quality green tea has less caffeine than a cup of coffee. About 10 mg less. L-Theanine + Caffeine stack One study done at Unilever in the UK looked at the combined effects of L-Theanine and caffeine on cognitive performance and mood. They compared 50 mg of caffeine with and without 100 mg of LTheanine. The research team had 27 volunteers participate. And based measurements on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood. Performance was measured at the beginning, and again 60 minutes and 90 minutes after consumption. Separated by a 7-day washout period. Caffeine improved alertness at 60 mins. And accuracy on attention-switching at 90 mins. The LTheanine and caffeine combination improved both speed and accuracy, and reduced susceptibility to distracting information on the memory task. The research team concluded that, “L-Theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks”.461

And for an added bonus, L-Theanine takes the jittery-edge off of caffeine consumption. L-Theanine from green tea Extracting the optimal amount of L-Theanine from green tea is both art and science. Researchers at the University of Newcastle in Australia set out to determine optimal conditions for water extraction of L-Theanine from green tea. They examined 4 different extraction methods. And learned that temperature, extraction time, ration of water-to-tea and tea particle size had significant impacts on extraction yield of L-Theanine from green tea. They concluded, “The optimal conditions for extracting theanine from green tea using water were found to be extraction at 80 °C for 30 min with a water-to-tea ratio of 20:1 mL/g and a tea particle size of 0.51 mm.”462 So to get the most nootropic value when using green tea as your L-Theanine source – follow the directions. Just sayin’… L-Theanine Supplements L-Theanine is available in capsule or tablet form from several supplement manufacturers. Japanese company Taiyo is the oldest and most established company in the green tea supplement industry. Taiyo developed and patented a method for L-Theanine extraction from green tea called ‘Suntheanine®’. Suntheanine is included as the L-Theanine source from several large supplement makers including Mind Lab Pro®. And if it has Suntheanine on the label, you are assured that the amount of L-Theanine listed is the actual amount in each capsule. Research has shown that some supplement makers using their own extraction method for L-Theanine, contain more than just the “L” form of Theanine. Turns out if it’s not done exactly right, you end up with a “D” form of Theanine. D-Theanine may have a very different action in your body than L-Theanine. We’re not saying it’s dangerous. You just may not get all the benefit of pure L-Theanine. So read the labels and reviews by people who have tried the product. With a little experimentation you’ll find a L-Theanine supplement that works for you. Nootropics Expert® Recommendation L-Theanine 250 - 500 mg per day I recommend using L-Theanine as a nootropic supplement. Your body cannot make L-Theanine on its own. It’s a non-dietary amino acid only available from tea (and one little-known mushroom). L-Theanine affects Alpha and Theta brain waves. This alone will help calm your mind, reduce stress, and help you stay alert. You’ll get even more cognitive benefit by stacking L-Theanine with caffeine.

L-Theanine helps boosts the neurotransmitters dopamine, serotonin, and GABA. Improving alertness and attention. And boosting cognition and memory. And it reduces the excitatory neurotransmitter glutamate which is associated with stress, tension and agitation. L-Theanine helps to prevent strokes, and even reduces the damaging effects if you’ve had a stroke. And L-Theanine has been shown to improve sleep quality. I suggest starting with a dose of 100 - 250 mg of L-Theanine daily for nootropic use. Using either a quality supplement, or high quality green tea.

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Magnesium Magnesium improves cognition, memory, learning, recall, reduces brain fog, is an antioxidant, helps neuroplasticity, and protects against glutamate-toxicity Magnesium is the 4th most abundant mineral in your body. And critical for optimal cognitive health. It is a cofactor in more than 300 enzymatic reactions in your body.463 But many of us in Western society are living with a magnesium deficiency. And most are unaware of this deficiency. Magnesium in our diet comes from foods like green leafy vegetables, beans, nuts, seeds, whole grains, poultry, beef, and salmon. Tap, mineral and bottled water also used to be good sources of magnesium. But varies by brand, source and if the magnesium has been filtered out during processing. Magnesium assists in converting energy supplied by food to a useable form to produce adenosine triphosphate (ATP). The primary fuel source produced within your mitochondria. Magnesium is also needed for the synthesis of RNA and DNA.464 In your brain, magnesium regulates the activity in neuron ion channels. These channels are like tiny electrical switches. Governing the flow of neurotransmitters within neurons. Magnesium also regulates brain synaptic plasticity. Which is critical for learning and memory. Magnesium is critical to all of your body’s electrical and electrochemical activities. It’s involved in muscle contractions, heart rhythm, nerve function and brain cell activity. Low blood magnesium levels show up as seizures, hypertension, stroke, migraines, and ADHD. It can also result in insulin resistance and type II diabetes. Magnesium is an essential part of neuroplasticity. Brain plasticity is the ability of your neurons to make cell-to-cell connections to form and regulate learning and memory. With aging, or insufficient magnesium in our diet, we lose brain plasticity which results in a loss of cognitive function.465 This is why a young person, with an active, flexible brain easily catches new ideas. And simply thinks faster than a person whose brain has lost plasticity and is more fixed in their patterns. Magnesium is even involved in how the other nootropics in your stack are utilized by cells in your brain. The bottom-line is magnesium could be one of the most important additions to any nootropic stack. How does Magnesium Work in the Brain? Magnesium boosts brain health and function in several ways. But two in particular stand out. 1. Magnesium is critical for neuroplasticity. Your brain is capable of forming new connections

between neurons. When you take in new information, a signal is sent across the synaptic space between neurons. The ability of your brain to form these new connections is referred to as neuroplasticity. This neuroplasticity is how learning and memories are formed. When these signaling pathways break down, memories fade. And you start to forget simple things like people’s names or phone numbers. A simple example of how this works is reading this article. As you read this, your brain is forming and reforming new neural connections. When things aren’t optimal, you find yourself reading and rereading sentences. Magnesium is critical for maintaining this neuroplasticity. And your ability to learn and form memories. Magnesium ions control the ion channels, or electrical switches for this signaling.466 The more signals that these ion channels transmit, the stronger the connections between neurons. And the stronger the formation of the resulting memory. Many studies demonstrate the detrimental impact of insufficient magnesium on optimal cognitive function.467 2. Magnesium is required for ATP synthesis. ATP (adenosine triphosphate) is the main energy source produced within mitochondria in brain cells. 20% of your body’s total ATP is located in your brain. For ATP to be biologically active, it must be bound to a magnesium ion (Mg-ATP).468 About two thirds of your brain’s energy budget is used to help neurons send signals to neighboring neurons. The remaining third is used for housekeeping, or cellular maintenance. Wei Chen, a radiologist at the University of Minnesota Medical School was co-author of a study on the brain’s use of ATP. The team used magnetic resonance spectroscopy (MRS) to measure the brain’s energy production during shifts in activity. Their study on lab rats noted that when the rats were knocked out, they produced 50% fewer ATP molecules than when mildly anesthetized. Chen noted that the ATP produced when the brain is inactive goes to cell maintenance.469 This housekeeping is important for keeping the brain tissue alive. The other two thirds are needed for other cellular processes including recharging neurons so they can fire. And create the electrical signals needed for neuron communication. Required for learning, memory, recall and cognition. Without magnesium, your brain cannot produce ATP, and all brain function breaks down. How things go bad As we get older, our brain chemistry and metabolism changes. ↓ ATP levels decline in mitochondria

↓ Cognition, learning, memory and recall decline ↓ Brain cell plasticity declines ↓ Free radicals damage brain cell mitochondria All of these changes can happen at any age. And can be a result of not getting an adequate supply of magnesium. So magnesium supplementation can help for age-related cognitive decline, as well as anyone who wants to boost cognition, learning, recall and memory. Magnesium benefits Magnesium plays a critical role in supporting neuroplasticity which is fundamental for a youthful, flexible brain. A brain that is optimized to support cognition, learning and memory. Raising brain magnesium levels has been proven to restore neuroplasticity and improve cognitive function.470 Magnesium deficiency has been associated with Alzheimer’s Disease. Scientists have found that treatment with magnesium-L-threonate decreases β-amyloid deposits in the brain. And is able to rebuild signaling pathways in neurons helping to restore memory.471 And magnesium is required for ATP synthesis in brain cells. Providing the mental energy needed for cognition, memory, recall and learning.472 How does Magnesium feel? Most neurohackers report an increased level of focus, energy, memory, and cognitive ability when supplementing with magnesium. You should also experience an improved quality of sleep. And have an overall improvement in mood. The Research One of most common reasons we use nootropics is to boost memory and mental energy. Memory loss drastically reduces quality of life. And simple brain fog makes it difficult to accomplish the simplest of tasks. Research has shown that magnesium is involved in memory, learning and cognition on several levels. And supplementing with magnesium is one of the most fundamental things you can do to boost cognition. Magnesium improves long-term memory Synapses in the hippocampus and other areas of the brain strengthen the more they’re used. Even brief repetitive activity results in a substantial increase in synaptic strength. The results can last for several hours. Or even weeks afterwards. This is called ‘long-term potentiation’.473

Several studies have been conducted on magnesium supplementation and its effects on memory in the last 20 years. With positive results. This study on aged and young rats found that adding magnesium to their food improved learning.474 Magnesium relieves depression Researchers have found magnesium works in the hippocampus to suppress the release of the stress hormone ACTH (adrenocorticotrophic hormone). This is the hormone that tells your adrenal glands to release more cortisol and adrenaline. Too much cortisol eventually damages the hippocampus in the brain. This causes a negative feedback loop which results in even more stress. Which is toxic to the brain and your entire body. And one of the causes of chronic depression. A study was done with 5,708 people aged 46-49 and 70-74 years old in Norway. The aim of the study was to examine the association between magnesium intake and depression and anxiety. The researchers concluded that low magnesium intake is related to depression. And they stated, “These findings may have public health and treatment implications.”475 Another study done with 12 subjects found that magnesium supplementation improved sleep and lowered the stress hormone cortisol. Concluding that magnesium has “possible efficacy… as a mood stabilizer”.476 Magnesium may relieve symptoms of ADHD Magnesium in the treatment of ADHD is becoming more mainstream. And there is a growing body of research that supports the idea that one of the factors causing ADHD is a lack of magnesium. A study in Poland showed that 95% of the children examined with ADD or ADHD were magnesium deficient.477 Dosage Notes Recommended magnesium dosage in most common forms is 400 mg per day. But the problem is most magnesium supplements don’t work well as a nootropic. Because they don’t cross the blood-brain barrier. Research begun at MIT by Dr. Inna Slutsky came up with a new magnesium supplement called Magnesium-L-threonate (MgT). This new magnesium compound easily crosses the blood-brain barrier.478 This form of magnesium was patented and now produced by Magtein™ Science. Several supplement companies sell magnesium with this branded form. Recommended dose of Magnesium-L-threonate is 1 gram per day. Magnesium is water-soluble so you don’t need to take it with a meal, or a healthy fat like you do with some nootropics.

Side Effects Most forms of magnesium can cause diarrhea and bloating. Magnesium-l-threonate contains less elemental magnesium per dose and should not cause gastrointestinal upset. Available Forms Magnesium is sold as magnesium aspartate, citrate, lactate, chloride and magnesium L-threonate. Depending on the type of magnesium; it comes in capsules, chewable tablets, powder, extended-release tablets, or in a liquid solution. A more bioavailable form of magnesium is now available. Magnesium-l-threonate (MgT) is patented and is called Magtein™. Magnesium-l-threonate easily crosses the blood-brain barrier. And is recommended if you’re adding magnesium to your stack. Nootropics Expert® Recommendation Magnesium-L-threonate 1 gram per day I recommend using Magnesium-L-threonate as a nootropic supplement. Your body does not make Magnesium on its own. So to get its benefits it needs to come from your diet. Or you must take it as a supplement. Magnesium is especially helpful for boosting memory, learning, recall, mood and cognition. Magnesium is also particularly useful to help alleviate some of the symptoms of ADHD. And to help restore memory caused by neurodegenerative disease like Alzheimer’s. While most forms of magnesium are helpful for overall health, most are not very helpful for cognitive health. I recommend Magnesium-L-threonate (MgT). MgT has been proven in the lab to easily cross the bloodbrain barrier. And to boost cognition. Magnesium-L-threonate is a fast-acting nootropic that can also help prevent brain degeneration later in life.

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Magnolia Bark Magnolia Bark is known for its anti-anxiety and stress-relieving effects, reducing depression, and promoting restful sleep. Magnolia Bark (Magnolia officinalis, Magnoliae cortex, Houpo, Chua houpu) comes from the Magnolia tree originally found in Southeast Asia, Eastern North America, Central America, and the Himalayas. Its flowers are fragrant with white petals.479 Magnolia Bark was first recorded in the “Shennong Herbal Classic” from the Qin and Han Dynasty around 221 B.C. to 220 A.D. It was used to get rid of phlegm, lower Qi, and for abdominal swelling. More than 250 different chemical compounds have been identified in the flowers, bark, and leaves of the Magnolia. But most of its therapeutic potential comes from the bark and roots. The Magnolia bud is almost exclusively used to treat sinus congestion and sinus headache.480 Magnolia Bark is harvested in the spring from April to June. The root and branch bark are boiled in water and set aside until it turns a purplish brown color. This concoction is then steamed, rolled, and dried. Early chemical studies identified two main active ingredients in the Magnolia Bark: magnolol and honokiol. These neolignanes are the main active components providing its nootropic benefit.481 Other bioactive compounds from Magnolia Bark are the alkaloids benzyl-tetrahydroisoquinoline and aporphine which are found in the leaves, branches, and bark. These alkaloids may also have antispasmodic and muscle relaxant benefits.482 Magnolia Bark has been traditionally used to treat diabetes, atherosclerosis, Alzheimer’s disease, gastrointestinal disorders, asthma, and microbial infections. Studies in human cells indicate a growth inhibitor effect of honokiol and magnolol on human melanoma and carcinoma cells. There is increased interest in developing a novel analogue for chemotherapy derived from Magnolia Bark.483 As a nootropic, Magnolia Bark interacts with the adenosine A1 receptor, dopamine transporter, dopamine D5 receptor (antagonist), serotonin receptors 5-HT1B and 5-HT6 (antagonist), GABAA receptors, hippocampus acetylcholine release, and modulates serotonin activity.484 And is an acetylcholinesterase (AChE) inhibitor.485 The compounds honokiol and magnolol found in Magnolia Bark have been shown to significantly decrease β-amyloid (Aβ)-induced neuronal death associated with Alzheimer’s Disease.486 And the compound honokiol found in Magnolia Bark is said by users to be as effective as diazepam for relieving anxiety with fewer side effects. How does Magnolia Bark work in the brain?

Magnolia Bark boosts brain health and function in several ways. But two in particular stand out. 1. Magnolia Bark is anti-anxiety. Magnolia Bark is known for its anti-anxiety benefits as an alternative to benzodiazepines.487 Honokiol found in Magnolia Bark has been shown to act on the GABAA receptor subunit α-2 which provides some of its anti-anxiety benefits.488 2. Magnolia Bark as an antidepressant. Main-stream psychiatric medicine often treats depression using SSRI’s. Which affects serotonin reuptake in the brain. Traditional Chinese medicine uses Magnolia Bark to treat depression instead. Studies have demonstrated the honokiol and magnolol found in Magnolia Bark help prevent decreases in serotonin in the frontal cortex, hippocampus, striatum, hypothalamus, and nucleus accumbens. The combination of honokiol and magnolol also normalize hypothalamic-pituitary-adrenal (HPA) hyperactivity. And induce reductions in platelet activity by upregulating the cAMP pathway. The results of these studies show how Magnolia Bark provides its potent anti-depressant benefits.489 There is also growing evidence that inflammation in the brain contributes to depression. Here again, Magnolia Bark has been shown to significantly reduce levels of pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Reducing inflammation in the brain may affect tryptophan metabolism which increases serotonin. Providing another way Magnolia Bark as a naturally effective option for dealing with depression.490 How things go bad Chronic stress, anxiety, poor blood flow and free radicals (oxidative stress) can damage your brain. And one of the ways this manifests is memory loss. It comes as no surprise that people with memory loss experience higher rates of anxiety and depression. ↓ Chronic stress reduces memory capacity ↑ inflammation kills brain cells ↓ Free radicals destroy neurons and synapses ↓ Acetylcholine (ACh) levels decline ↓ Learning and memory decline Magnolia Bark helps reduce inflammation, restores acetylcholine levels, and supports memory. Magnolia Bark benefits Magnolia Bark taken as a nootropic supplement easily crosses the blood-brain barrier helping reduce oxidative stress in the brain and throughout the body.

Magnolia Bark is widely used to elevate mood, decrease pain, and improve immune health. Magnolia Bark activates cannabinoid receptors in your brain. Cannabinoid receptors include CB1 and CB2. CB1 receptor activation regulates memory, cognition, and motor control. Relieving pain, vomiting, reducing hyperexcitability in epilepsy, stimulates appetite, and euphoria. CB2 receptor activation provides pain relief and reduces inflammation.491 Magnolia Bark helps reduce stress by suppressing adrenaline and maintaining healthy cortisol levels. Studies have shown that honokiol works as effectively as the anti-anxiety drug Valium® (diazepam) without the associated side effects.492 And Magnolia Bark extract helps prevent memory loss because of its anti-inflammatory effects in your brain. How does Magnolia Bark feel? Neurohackers report that supplementing with Magnolia Bark provides an anti-anxiety effect within minutes of taking it. Some users say it works as well as diazepine. Most say they feel relaxed and ready to sleep after taking Magnolia Bark. Using it as a sleep supplement helps them fall asleep and stay asleep throughout the night. But dosage is important. And many users say you will not get the benefits of Magnolia Bark if you don’t follow dosage recommendations. Feelings of anxiety and depression can be reduced significantly with Magnolia Bark daily supplementation. Most report that Magnolia Bark is a great way to quickly reduce stress. Magnolia Bark Clinical Research Most of the clinical research for Magnolia Bark are animal studies with very few conducted with humans. Magnolia Bark is anti-anxiety Magnolia Bark has long been used as an anxiolytic. Most users report a reduction in anxiety when using it as a supplement. A 2013 review by researchers at Emory University in Atlanta found that the compound honokiol in Magnolia Bark interacts with the GABAA receptor. The same receptor targeted by anti-anxiety drugs like diazepam and without the side effects caused by benzodiazepines.493 Another study at the University of South Carolina School of Medicine reported that magnolol and honokiol enhanced both pre-synaptic and post-synaptic GABA transmission in hippocampus neurons.

Magnolia Bark modulated all sub-receptors in this group regardless of the α, β, or γ subunit subtype. Suggesting that supplements containing magnolol and/or honokiol would be effective anxiolytics, sedatives and anti-convulsants. But the researchers also noted side-effects and significant risk of drug interactions could also be expected.494 Magnolia Bark for sleep User reviews of Magnolia Bark extract supplements often report using it for sleep. Studies show Magnolia Bark holds promise for those who have trouble falling and staying asleep. The compound honokiol significantly shortened the time to fall asleep to non-rapid eye movement (non-REM, NREM) sleep and increased the amount of non-REM sleep in animal studies. Honokiol increased the number of state transitions from wakefulness to non-REM sleep, and from nonREM sleep to wakefulness. But honokiol has no effect on either the amount of REM sleep or depth of sleep. The study concluded that “honokiol promoted NREM sleep by modulating the benzodiazepine site of the GABAA receptor, suggesting potential applications in the treatment of insomnia, especially for patients who experience difficulty in falling and staying asleep.” Clearly, those who use Magnolia Bark extract for insomnia have the clinical evidence to back up their claims.495 Magnolia Bark may prevent seizures A study was conducted in Belgium with the aim of discovering natural compounds that could be further tested for the treatment of epilepsy. The researchers collected 14 herbs used in Traditional Chinese Medicine used to treat epilepsy. Of six extracts that tested positive in an animal model for epilepsy, only Magnolia Bark extract showed antiseizure activity.496 Honokiol has been shown to inhibit repetitive firing by blocking glutamate, NMDA and K+ evoked cationic influx. Both honokiol and magnolol were found to increase seizure thresholds but honokiol appeared to be more potent in animal studies.497 Magnolia Bark recommended dosage Manufacturers of Magnolia Bark extract generally recommend a nootropic dosage of up to 500 mg per day. Effective dosage depends on the strength of the extract. We do not have access to clinical data stating the maximum recommended daily dosage for Magnolia Bark. But do NOT exceed the recommended dosage because studies show in excess, Magnolia Bark can be

toxic and cause neuronal cell death.498 Magnolia Bark is fat-soluble and can easily cross the blood-brain barrier. Because it is fat-soluble, Magnolia Bark must be taken with a healthy fat like unrefined coconut oil or other healthy oil to ensure absorption. Magnolia Bark side effects Magnolia Bark is non-toxic and safe for use as a nootropic supplement based on years of recent food safety studies.499 However, although rare, side effects can include tremors, dizziness, excessive sleepiness, and muscle weakness. Do NOT use Magnolia Bark if you are on blood-thinning meds. And discontinue its use at least two weeks prior to surgery. Avoid using Magnolia Bark if you are pregnant or breastfeeding. One animal study documented honokiol and magnolol blocked calcium-dependent uterine contractions in rats.500 Magnolia Bark should NOT be used if you are taking benzodiazepines because studies show this powerful herb significantly increases the sensitivity of GABAA benzo receptors.501 Combining the drug with Magnolia Bark may result in a benzodiazepine overdose. Magnolia Bark extract can cause sleepiness, vertigo, and dizziness if you are using muscle relaxants. Magnolol in Magnolia Bark will stimulate corticosterone secretion which will likely cause problems if you are using steroid medication. We have reports spanning the last few decades of women developing kidney failure resulting in dialysis after using a Magnolia Bark supplement as part of a weight loss program. Further investigation showed different alkaloid profiles from those expected from Magnolia Bark. Which likely means something other than pure Magnolia Bark extract was used.502 The bottom-line is make sure you are buying a genuine and pure Magnolia Bark supplement. Type of Magnolia Bark to buy Magnolia Bark extract is available in capsules, tablets, bags of powder, loose bark tea, and liquid extract. Magnolia Bark extract is offered in various strengths. Including a certain percentage of honokiol and magnolol which are the two active compounds found in this herb. Relora® is a proprietary and patented blend of Magnolia Bark extract and Phellondendron amurense bark extract made by Lonza. And licensed for use by dietary supplement manufacturers. Relora® is supported by 3 peer-reviewed, randomized, double-blind, placebo-controlled studies

demonstrating a 42% improvement in mood states, 18% increase in vigor, 11% overall reduction in stress, and a 20% reduction in depression.503 Do your best to choose a Magnolia Bark extract supplement made in a GMP facility with no “other ingredients” other than the capsule. And a testing program in place ensuring quality and purity. Nootropics Expert® Recommendation Magnolia Bark extract up to 500 mg per day. I recommend using Magnolia Bark extract as a nootropic supplement. Your body does not make the compounds honokiol and magnolol found in Magnolia Bark on its own. So, to get its benefits you must take it as a supplement. Magnolia Bark is especially helpful for those dealing with anxiety and stress. Studies show and users report it as effective for taming anxiety as benzodiazepines. But without the side effects associated with these drugs. Magnolia Bark is reported to work well for those suffering from insomnia. Taken as a sleep aid, Magnolia Bark extract helps you fall asleep faster, and stay asleep. Magnolia Bark extract is also helpful for those suffering from Alzheimer’s. It acts as an acetylcholinesterase inhibitor which increases acetylcholine levels often lacking in the Alzheimer’s brain. This nootropic herb helps relieve symptoms of depression by maintaining healthy serotonin levels. And reducing the pro-inflammatory cytokines often found elevated in those with depression. Keep in mind that Magnolia Bark is fat-soluble and requires healthy fats from a meal, or a tablespoon of unrefined coconut oil or MCT Oil for absorption.

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Medicinal Nootropic Mushrooms Mushrooms have been used by humans for thousands of years as food and medicine. More than 14,000 species of mushrooms have been identified and about 2,000 of them are edible. Of 2,000 edible mushrooms, 270 species have potential therapeutic or preventative agents that ensure human health. But of 270 medicinal mushrooms, only 6 are considered nootropics. And provide some type of benefit for your brain. In this chapter you’ll discover the nootropic value of those 6 mushrooms. Including how they benefit learning and memory, anxiety, fatigue, and the potential for Alzheimer’s Disease. Then you’ll learn how to identify a genuine nootropic mushroom supplement. We’ll also cover how to avoid misleading marketing tactics that could trick you into buying bogus mushroom supplements. And the last section of this chapter provides suggestions on where to buy the highest quality nootropic mushrooms. Top 6 Nootropic Mushrooms 270 species of edible mushrooms have been researched and tested as providing therapeutic or preventive benefits. But so far, only 6 mushroom species have been identified with plenty of evidence to work as a nootropic and benefit your brain. Chaga (Inonotus obliquus) Chaga mushrooms grow naturally on the bark of birch trees in northern Canada, Alaska, Siberia, Northern Europe, and Korea. Traditional medicine in the Northern Hemisphere used Chaga Mushrooms to inhibit cancer progression, stimulate immunity, reduce inflammation, and liver protection.504 In the lab, Chaga has been shown to be antitumor, anti-mutagenic, antiviral, antidiabetic, antioxidant, and analgesic (pain relief). Animal studies demonstrated Chaga as an acetylcholinesterase inhibitor which boosts acetylcholine for better learning and memory.505 Another study showed Chaga is a potent antioxidant and free radical scavenger.506 Do not use Chaga Mushrooms if you’re on blood thinning medication, diabetes medication or if you have kidney disease. Chaga is high in oxalates, which may prevent the absorption of some nutrients and can be toxic in high

doses. Chaga Mushroom is available in capsules, bottled tinctures, as an extract, in tea bags, and fresh raw mushroom. Dosages vary between brands. Other than as an extract, Chaga is best absorbed in hot water, alcohol, or fermented. If you’re using Chaga powder or tea bags, let it steep in hot water for 5 minutes before using it. Cordyceps (Cordyceps militaris) In the wild, Cordyceps (sinensis) grows as a parasitic fungus on caterpillars. Cultivated Cordyceps (militaris) which is mass produced for the supplement industry has been found to have similar components as sinensis. And may yield higher quantities of active compounds.507 Cordyceps mushrooms have been used in traditional Chinese medicine to treat fatigue, respiratory and kidney disease. Over 200 clinical studies show Cordyceps mushrooms improves performance by increasing blood flow, boosts ATP synthesis for more natural energy, acts as an antioxidant, enhances lactate clearance, increases the release of catecholamines, and reduces oxidative stress, and fatigue.508 Cordyceps first gained attention in 1993, when world record-breaking performances of Chinese female athletes were attributed to a vigorous training and nutrition regimen that involved Cordyceps supplementation.509 A study conducted in Japan showed significant increases in the concentrations of creatine, and all the catecholamines in men over of the course of 2 weeks who were supplementing with Cordyceps sinensis. The researchers concluded that “during this prolonged exercise, ingesting with Cordyceps mushrooms might elicit the superior efficiency and the economical function on the energy metabolism”.510 You will get the most benefit of supplementing with Cordyceps by using 4 grams per day for at least 3 weeks. Lion’s Mane (Hericium erinaceu) Lion’s Mane Mushroom is an ancient Chinese remedy for improving cognitive performance, and for overall health. Known for its powerful effects as a “brain tonic”, Lion’s Mane is said to have been used as a tea for thousands of years by Buddhist monks. To enhance brain power and heighten their ability to focus during meditation. Lion’s Mane stimulates enzyme production that releases Nerve Growth Factor (NGF). In a study done in Kuala Lumpur in 2013, scientists showed that Lion’s Mane extract induced NGF synthesis and promoted neurite outgrowth.511 Nerve Growth Factor helps repair neurons in your brain and boosts the growth of new neurons

(neurogenesis). For better learning and memory. Dosage of Lion’s Mane depends on the strength of the extract. Ranging from 300 mg to 3000 mg dosed 1 – 3 times per day. Maitake (Grifola frondosa) The Maitake mushroom is native to northeastern Japan. Its rippling appearance with no caps is a bit like that of dancing butterflies. Hence its name is derived from the Japanese words Mai (dance) and take (mushroom). Maitake mushrooms are used to support some cancer therapies, chronic fatigue, hepatitis, allergies, high blood pressure and cholesterol. Its nootropic value comes from its ability to relieve depression. Studies show that the expression of AMPA receptors are reduced in patients with depression.512 And antagonists that sensitize AMPA receptors help prevent depression. Animal models show that supplementing with Maitake provides an antidepressant effect by sensitizing AMPA receptors. And the researchers concluded that “patients may just eat Maitake as a supplement for the treatment of depression”.513 Recommended dosage of Maitake Mushroom extract is 250 – 500 mg per day. Oyster (Pleurotus ostreatus) Oyster mushrooms are of Asian origin, but first cultivated in Germany during the first World War as an alternative food source. It’s now the 3rd highest in quantity of the commercially produced mushrooms worldwide. Oyster mushrooms are high in protein and a good alternative to animal meat because they contain some of the same amino acids as found in animal protein. Making Oyster mushrooms a good protein source for vegetarians. Oyster mushrooms are also a good source of the B-Vitamins, Vitamin C, Vitamin D, and several minerals.514 The nootropic benefits of Oyster mushroom extract are attributed to and include anti-bacterial, antiviral, antitumor, anti-inflammatory, and works as an antioxidant by suppressing oxidative stress and as a free radical scavenger. Trials are undergoing and testing Oyster Mushrooms ability to degrade plastic waste, crude oil, and even radioactive waste.515 Reishi (Ganoderma lucidum) Reishi mushroom has been used for over 2000 years in traditional Chinese Medicine.

In China, G. lucidum is called lingzhi. In Japan, the name for the Ganodermataceae family is reishi or mannentake.516 Reishi mushroom benefits include blood sugar regulation, antioxidant, antibacterial, antiviral, and antitumor.517 As a nootropic, Reishi is used for its anti-anxiety benefits518 and for chronic fatigue syndrome. A study at Mae Fah Luang University in Thailand recruited 50 volunteers suffering Chronic Fatigue Syndrome. Each were given Reishi mushroom extract or placebo. Each person was asked to respond to a questionnaire for quality-of-life score and level of fatigue before and 4, 8, and 12 weeks after the first dose. At the end of the study, those who used Reishi mushroom extract reported a significant increase in quality of life compared to placebo with a decrease in fatigue. The researchers concluded that “G. lucidum extract could be potentially effective in the treatment of fatigue and improve quality of life in Chronic Fatigue Syndrome patients.”519 Many ‘in-vivo’ studies demonstrate the benefits of Reishi mushroom to include boosting your immune system,520 preventing abnormal blood vessel formations, it’s anti-tumor, and helps reverse liver damage. Another animal study showed that Reishi mushroom could play an important role in Alzheimer’s Disease treatment. And as a nootropic, it supports the growth of Nerve Growth Factor (NGF).[xviii] NGF boosts learning, memory, and longevity. Reishi mushroom is available in capsules, as a powder, and as an extract. Dosages vary depending on the strength or how concentrated the extract. The Pharmacopoeia of the People’s Republic of China recommends 6 to 12 g reishi extract daily. How to Buy Genuine Nootropic Mushrooms The beauty of mushrooms as a food and the few that are considered for their nootropic cognitive benefit is that they’re natural, and free of pesticides. And as nootropics or functional food, are high in vitamin, mineral and protein content. As well as being neuro-active and as antioxidants. But a word of caution here. You can usually find any of the 6 mushrooms I detailed above in a vitamin shop or online for use as a nootropic supplement. But the challenge is choosing nootropic mushroom supplements that work as claimed. How the mushroom is grown and processed as well as the part of the mushroom used will affect its value as a nootropic.

Just one of many examples, the processing method (oven-dried vs freeze-dried) for Lion’s Mane Mushroom has been shown to affect its neurite stimulation activity.521 Here you’ll learn about the different parts of a mushroom. And depending on how its grown and the part used, which supplements will offer the most nootropic value. Choose the wrong supplement and you won’t get its benefit. Unfortunately, manufacturers often make it difficult to discern what method was used to make their mushroom supplement. Once you learn how to read the label, you’ll have more confidence knowing you’re buying the best nootropic mushrooms. Understanding the Market of Nootropic Mushrooms What we call a “mushroom” is made up of two parts – the mycelium and the fruiting body. The top of the mushroom is the fruiting body. And its stem is the mycelium. NOTE: mycelium and mushroom is not synonymous. If the supplement label states that the contents are ‘mycelium’, you’ll know you’re NOT getting a mushroom supplement. More on that in the next section. The active components in a mushroom are what dictate their benefit to your cognition and overall health. Those active components are beta-D-glucans, triterpenoids and ergosterol.522 Beta-D-glucans are the primary source of nootropic activity. They make up the natural structural component of the cell walls of the fruiting body of the mushroom. Triterpenoids compliment beta-D-glucans in immune system activity. And along with Ergosterol offer antioxidant activity, reduced inflammation, liver protection and reduced histamine response. Genuine Mushrooms vs Mycelium What you refer to as a ‘mushroom’ is actually the ‘fruiting body’ of the mushroom. Which develops from a spore, grows into the mycelium, and then tops it off with a mushroom (fruiting body). Mycelium is the underground network that acts like a root which feeds off of organic plant matter. This plant matter is usually referred to as substrate. The mycelium becomes woven into whatever that substrate is and is inseparable from the substrate material. If all goes well, the mycelium produces a mushroom (fruiting body). The fruiting body is the reproductive mechanism of this organism. When fully mature, the fruiting body produces spores that enter the substrate matter. To go on to produce more mycelium.

The bottom-line is a mushroom is not mycelium, and mycelium is not a mushroom. The only exception to this ‘rule’ is Lion’s Mane Mushroom. Because the fruiting body does not contain erinacines which is the compound that boosts Nerve Growth Factor (NGF). The nootropic benefits of hericenones are only found in the fruiting body or top of the mushroom help support your immune system and get rid of Amyloid β(25-35) peptide implicated in diseases like Alzheimer’s. The challenge is getting a Lion’s Mane Mushroom extract that contains the full spectrum found in both the mycelium and fruiting body. But the mushroom must be grown in liquid and not a solid substrate like grain. Otherwise you’ll get ground up grain without the important erinacines needed for increased NGF. The nootropic value of mushrooms: beta-D-glucans Functional nootropic mushroom benefits come from their active compounds which are found primarily in the mushroom (fruiting body). And much less so in the mycelium. The fruiting body contains Beta-D-glucans which modulate your immune system, reduce inflammation, control blood sugar, help reverse fatigue symptoms, and increase overall performance endurance.523 As the mycelium grows down into the substrate matter the two become interwoven. And cannot be separated during processing when manufacturing supplements. Mushroom supplement manufacturers often claim their product is pure “mushroom” extract. But what you may be getting instead is a mycelium supplement combined with substrate matter. Check the ‘Supplement Facts’ label on the back of a “mushroom” supplement to ensure you’re getting the “fruiting body” and not “mycelium” instead. Polysaccharides does NOT Equal Mushroom Quality Polysaccharides is another term you’ll come across on mushroom supplement labels. Truth is they are a key component in nootropic mushrooms. And companies boast about their high polysaccharide numbers. But here’s the problem with evaluating a mushroom supplement simply by measuring polysaccharides. Polysaccharides are long chain carbohydrates made up of components like beta-glucans, chitin, cellulose, glucose, and fructose. But polysaccharides also include alpha-glucans such as glycogen, dextran, pullulan, and starch. Many so-called “mushroom” products are made up of alpha-glucans and not beta-glucans. The thing is a lot of medicinal mushroom supplements on the market are just mycelium which is grown on grain. And the grain cannot be separated from the mycelium that it’s entangled with.

These grains are alpha-glucans, starches, and other fillers which are part of the grain substrate the mushroom is grown on. And are passed off as “mushroom” supplements to those who haven’t done their homework. Alpha-glucans provide no nootropic benefit. Unless you inspect the nootropic mushroom label carefully, you may be misled into believing that you are buying a genuine mushroom supplement. When in fact, you could be buying a bottle filled with mycelium/grain powder. Six researchers conducted and published a study in partnership with the US Pharmacopoeia to evaluate 19 Reishi mushrooms. The supplements were purchased online from Amazon and eBay. Only 5 of the 19 supplements tested contained genuine Reishi mushroom. The supplements evaluated in this study included 6 fruiting body powders, 1 fruiting body powder with added polysaccharides, 1 reishi mycelium product and 11 extracts. The researchers concluded that several so-called ‘Reishi’ mushroom supplements did NOT contain what consumers expected based on product information and labels.524 The big take-away here is just because you see a picture of a mushroom on the front of a supplement bottle does NOT guarantee any genuine mushroom fruiting body in the supplement. To get the most potent nootropic mushroom supplement, look for extracts made from the mushroom (fruiting body) and which also specifies beta-glucan content. Do NOT buy a mushroom supplement if the manufacturer neglects to state the part of the mushroom they use. The bottle or package should say whether you’re getting the mushroom (fruiting body), the mycelium, or a blend of both. How much of each including the percentage (%) of beta-glucan content. If not, put it back on the shelf. Summary China is the leading grower worldwide of medicinal mushrooms accounting for 90 – 95% of world production. China first began growing mushrooms for food and medicine in the 13th century. Many of the research centers dedicated to the study and development of mushrooms are in China. Mushrooms grown in the United States or Canada are too expensive for nootropic supplement use. If your supplement label states “Made in the USA” double-check and make sure that you are buying genuine mushroom. Because if it’s an extract and whole “fruiting body”, the mushrooms are grown China. Even if the extract was manufactured in the USA. If the company insists their product was grown in the USA or Canada, you can be sure that the contents

of that supplement are mycelium/grain powder and not genuine mushroom (fruiting body). When choosing a nootropic mushroom it’s important to keep in mind that for you to get it’s nootropic benefit it needs to be 100% mushroom (fruiting body), with verified levels of beta-glucans, zero fillers, and preferably certified organic.

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Melatonin Melatonin is known for helping insomnia, is a powerful antioxidant and anti-inflammatory, protects against neurodegenerative diseases, stroke and brain trauma Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced in your pineal gland. Melatonin is often referred to as the “sleep hormone”. As your body’s central clock, melatonin tells your body, brain and organs when to be active and when to take a break and rest. Your pineal gland is a pea-sized organ located in the center of your brain and shaped like a tiny pine cone (hence its name). Your pineal gland is filled with cells that respond to light and darkness. Many Eastern traditions refer to the pineal gland as the “third eye” for this reason. Your pineal gland acts as your body’s central clock through its secretion of melatonin. Telling your brain, body, and organs when it’s time to be active and when it’s time to rest. This is the reason why melatonin is referred to as the “sleep hormone”. Melatonin and the neurotransmitter serotonin are both derived from the amino acid L-tryptophan. First L-tryptophan is hydroxylated by the enzyme tryptophan hydroxylase. The intermediate is decarboxylated by PLP and 5-hydroxy-L-tryptophan (5-HTP) to produce serotonin (5-HT or 5hydroxytryptamine). Serotonin acts as a neurotransmitter on its own. But is also converted into N-acetyl-serotonin by the enzymes serotonin N-acetyl transferase and Acetyl-CoA. Hydroxyindole O-methyl transferase and SAMe convert N-acetyl-serotonin into melatonin through methylation of the hydroxyl group.525 This process is first fueled by the tryptophan you get from foods like turkey, chicken, tuna, oats, bananas, peanuts, and chocolate. Or from a L-tryptophan supplement. You can also supplement with 5-HTP to produce serotonin which will create melatonin. Or supplement with SAMe to produce melatonin. Or you can take a melatonin supplement on its own and bypass this entire process. Besides acting as your body’s biological clock, melatonin is also a potent free-radical scavenger. And a wide-spectrum antioxidant. The beauty of melatonin as an antioxidant is its ability to easily cross the blood-brain barrier. Age-related decline in melatonin levels is a primary contributing factor to several neurodegenerative diseases including Alzheimer’s, Parkinson’s, ALS, Huntington’s Disease, stroke, and brain trauma.526 Adding melatonin to your nootropic stack gives you a head-start in protecting yourself against Alzheimer’s and Parkinson’s Disease, decreases your chance of stroke, and helps reverse the brain damage caused by stroke or brain injury. The bonus is a good night’s sleep and feeling refreshed the next day. With your brain firing on all

cylinders. How does Melatonin work in the Brain? Melatonin helps brain health and function in several ways. But two in particular stand out. 1. Melatonin promotes quality sleep. Your pineal gland acts as your body’s central clock by secreting melatonin. This action tells your brain and other organs when it’s time to be active, and when it’s time to rest. Melatonin helps regulate other hormones and maintains your body’s circadian rhythm.527 Your pineal gland responds to darkness by producing melatonin. Blood levels of melatonin are low during the day, with peak levels occurring from 2 – 4 AM.528 One study at Duke University Hospital surveyed clinical trials from 1948 – 2009. Researchers found that children with ADHD using melatonin doses of 3 – 6 mg showed improvement in how fast the kids went to sleep. And significantly better quality of sleep.529 Another extensive survey of clinical trials was conducted by the U.S. Department of Health and Human Services on melatonin use for sleep disorders. The overall conclusion of this research showed melatonin effective in improving quality of sleep and how fast a person went to sleep. This study included those who did not suffer with insomnia, those who did, and others who had messed up circadian rhythm patterns due to shift work and jet lag.530 2. Melatonin prevents neurodegenerative disease. Melatonin improves longevity by increasing the longevity gene called SIRT1. This gene plays an important role in maintaining metabolism and neuroplasticity.531 Melatonin is a powerful antioxidant protecting your brain from free radicals and oxidative damage. It stimulates gene expression of intracellular antioxidant systems. And melatonin helps relieve the free radical damage that occurs after traumatic brain injury or stroke.532 Research has found that melatonin levels and Alzheimer’s Disease are closely linked. Greatly reduced melatonin levels have been found in Alzheimer’s patients.533 High levels of melatonin are maintained throughout your youth and middle age. But as you age and melatonin levels drop, you are at greater risk for brain damage both now and in the future. Your chances of having a stroke greatly increase as melatonin levels decline.534 How things go bad Low Melatonin levels are associated with a variety of health problems. Much more than just insomnia. ↑ Insomnia, restlessness and poor sleep quality (sundowning) ↓ Circadian rhythm goes out of sync ↑ Agitation and activity increases later in the day (sundowning)

↓ Benzodiazepines like Valium® and Xanax® suppress melatonin levels535 ↑ Stroke risk increases Melatonin deficiency is one of the earliest indicators of Alzheimer’s Disease.536 Abnormal oxidation and inflammatory protein accumulation can lead to Parkinson’s Disease. And is associated with low levels of melatonin in the brain. Low levels of melatonin lead to increased free radical production and risk of stroke goes up. Oxidative damage to brain cells is a leading culprit in traumatic brain injury. Melatonin benefits Melatonin is both a neurotransmitter and hormone. This ‘neurohormone’ is produced in your pineal gland from the neurotransmitter serotonin with the assistance of SAMe and other enzymes. Melatonin is the mechanism used by your pineal gland to function as your body’s biological “clock”. And is in charge of the “circadian rhythm” that tells your system when to be active, and when to rest. As a nootropic supplement and sleep aid, melatonin exerts its effects by acting as a ‘phase re-setter’ rather than as a hypnotic-type drug. Supplementing with inexpensive melatonin helps restore your body’s natural antioxidant protection. Guarding against age-related changes in your brain. Melatonin protects cholinergic neurons from the amyloid and tau protein buildups related to Alzheimer’s Disease. Melatonin offers potent antioxidant protection for your brain. Supplementing with melatonin helps protect your brain against neurodegenerative disease, reduces stroke risk and guards against brain trauma. How does Melatonin feel? I use melatonin every night to help me sleep. I open and empty 3 mg of a Now Foods 5 mg melatonin capsule in about 4 oz. of tart cherry juice. And take it 90 minutes before bedtime. Sleep comes on within 5 minutes of hitting the pillow. And I sleep through the night. But melatonin as a sleep aid has mixed reviews among neurohackers. And for good reason. Melatonin is a hormone that your body naturally produces from serotonin. Too much melatonin is not good. Some find that supplementing with melatonin works well, and others find it disrupts sleep patterns. If you are perfectly healthy and do not deal with insomnia on a regular basis, you don’t need to supplement with melatonin. Everyone’s body chemistry is unique. Some find that a ½ mg of melatonin works well. And others require 5 mg. Experimentation is key with this hormone. Some have found that melatonin helps regulate disrupted circadian rhythms caused by jet lag or night

shift work. The Research Melatonin Lowers Cholesterol Melatonin levels decrease as we age, and the possibility of heart disease increases. And studies in the last 10 years show that melatonin and your cardiovascular system are linked. Patients with cardiovascular disease have decreased melatonin levels. Studies also show that people with heart disease have high levels of LDL-cholesterol. Research has found that supplemental melatonin decreases cholesterol by 38%. And reduces LDL accumulation by 42%. One study demonstrated that just 1 mg of melatonin reduced blood pressure within 90 minutes of supplementation. Melatonin reduces blood pressure through its antioxidant properties, by decreasing norepinephrine and epinephrine, and relaxing the smooth muscle of the heart aorta wall.537 Melatonin Helps Reduce Insomnia Studies show that sleep disorders affect 50 – 70 million Americans, or about 20% of the population. A sleep disorder exists whenever a lower quality of sleep results in impaired functioning, or excessive sleepiness. Insomnia is the most common sleep disorder affecting 6 – 12% of the adult population. A double-blind placebo-controlled study in France worked with 244 adults with primary insomnia. Patients received prolonged-release melatonin nightly for up to 12 months of the trial, followed by a 2week withdrawal period. Outcome was measured based on the patient’s sleep diary, adverse events, vital signs and lab tests recorded at each visit. The study concluded that prolonged-release melatonin was helpful in relieving insomnia during the trial. And patients did not experience any adverse events or withdrawal symptoms when they stopped using melatonin.538 Melatonin Relieves Mild Cognitive Impairment Mild cognitive impairment (MCI) is often the final step before dementia. Approximately 12% of MCI patients convert to Alzheimer’s Disease or other dementia disorders every year. Researchers in Argentina took a look at the first and final assessment of 50 MCI patients, 25 of whom had received a daily dose of 3-9 mg of melatonin at bedtime for 9 – 18 months. Patients who took melatonin showed significantly better performance in the mini Mental State examination and the cognitive test used to assess Alzheimer’s. The team conducted several other tests and found better performance in every test but one. The researchers concluded that melatonin can be a useful drug for treating mild cognitive impairment.539 Melatonin Replaces Benzos for Sleep

Many people use benzodiazepines for sleep. Drugs like Xanax®, Valium® and Ativan® all have nasty side effects. And studies going back 25 years show benzos depress natural melatonin levels.540 This is a problem because drugs taken for sleep are depleting the very hormone your body uses for sleep. To make matters worse, regular benzodiazepine use is now recognized as putting you at greater risk for dementia.541 This study done in Argentine had subjects use fast release melatonin 3 – 9 mg daily for 3 years just before bedtime. And it significantly improved cognitive and emotional performance. Including the daily sleep-awake cycles of patients. A follow up study was done with 91 MCI patients. 61 patients received 3 – 24 mg of fast release melatonin at bedtime for 15 to 60 months. Patients given melatonin showed significantly better cognitive performance and every other parameter tested. Depression scores in the patients also decreased. And showed an improvement in quality of sleep and wakefulness. Before the study began, 62.8% of the patients were using benzodiazepines to help them sleep. At the conclusion of the study only 9.8% were using benzos to help them sleep along with melatonin.542 My recommendation is if you are using one of these drugs for sleep, it would be wise to start using melatonin instead. And start weaning yourself off the benzos. Dosage Notes Unlike all the other nootropics we talk about on Nootropics Expert, and in this book, there is no recommended dosage for melatonin supplementation. Everyone has different responses to its effects. Lower doses like ½ mg of melatonin work well for some who are especially sensitive. And higher doses can cause anxiety and irritability. The best approach is to start with very low doses of melatonin (i.e. ½ mg) and see how your body reacts. The right dose should produce a restful night’s sleep with no irritability or fatigue the next day. For jet lag: ½ - 5 mg of melatonin an hour before bedtime at your final destination. Side Effects Melatonin is considered very safe when taken in normal recommended low doses. Some may experience nightmares or vivid dreams when supplementing with melatonin. Melatonin can cause drowsiness if taken during the day. And if you experience a “sleep hangover” the next day, you took too much melatonin the night before. Other side effects include abdominal cramps, dizziness, headache, irritability, decreased libido, breast enlargement in men and reduced sperm count.

Melatonin can interfere with fertility if you’re trying to get pregnant. Do not use melatonin while you’re pregnant. Melatonin can worsen symptoms of depression. So if you’re dealing with depression or are using antidepressant medications you should avoid melatonin. Remember that melatonin is a hormone. So if you have hormone-related issues you must be careful about using melatonin. Melatonin may increase the risk of bleeding and should be avoided if you’re taking anticoagulant medications. Or are anticipating surgery. Melatonin can interfere with steroids and immunosuppressant medications and cause them to lose their effectiveness. Available Forms Melatonin is available in capsules, tablets, and liquid. Capsules and tablets usually range from 1 – 5 mg. Nootropics Expert® Recommendation Melatonin 1 – 3 mg per day. I recommend using melatonin as a nootropic supplement. But see my review above on how melatonin supplements vary and how melatonin supplement labels can be misleading. Your body does make melatonin on its own from serotonin in your brain. Most healthy people have an adequate supply of melatonin. But if you’re dealing with insomnia and need some extra help in getting to sleep and staying asleep, melatonin can help. Melatonin easily crosses the blood-brain barrier, and takes effect in about 90 minutes. Avoid taking melatonin immediately before bed because you may have trouble falling asleep. Melatonin is especially helpful to those dealing with jet lag or shift work that has you working nights. Disrupted natural circadian rhythms can be normalized by supplementing with melatonin. I suggest first trying a melatonin supplement at a dose of ½ - 1 mg taken 90 minutes before bedtime. And see how you feel. If you readily fall and stay asleep until morning you know you’ve got the dose right. Then adjust your dose up or down depending on how you react. Most people don’t need more than 0.5 – 5 mg per night.

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Methylene Blue Methylene Blue boosts mitochondrial energy, is anti-aging, and improves mood and memory Methylene Blue (methylthioninium chloride) is a synthetic compound used as a nootropic to increase memory, mood, and longevity. Soon after Methylene Blue was synthesized as a textile dye in the late 1800’s, it became the first synthetic drug to be used in humans for the treatment of malaria In the early 20th century, psychiatrists were using Methylene Blue in the experimental treatment of schizophrenia.543 Methylene Blue is currently being studied as potential therapy for mild cognitive impairment, Alzheimer’s and Parkinson’s disease, and other neurodegenerative disorders. All sharing a common problem with mitochondrial function. Your brain’s neurons rely almost entirely on mitochondria-derived energy. Failure of mitochondrial function can affect the rest of your body. But it’s particularly detrimental to your brain. This is where Methylene Blue steps in as possibly one of the most important anti-aging and neurological disease preventing nootropics, we have available today. As a nootropic, Methylene Blue quickly crosses the blood-brain barrier. It improves mitochondrial efficiency and respiration, acts as an antioxidant, and increases brain cell lifespan. Resulting in improved memory and mood. Here we’ll dive into over 140 years of research on how Methylene Blue helps your brain. Methylene Blue was first synthesized in 1876 by German chemist Heinrich Caro at BASF as an anilinebased dye for cotton staining. In 1891, German physician and Noble Prize recipient Paul Ehrlich pioneered the use of Methylene Blue in the treatment of malaria.544 Ehrlich discovered that when MB was injected into animals in the lab, it would quickly concentrate in the brain. And had an uncanny ability to selectively target diseased tissues in the body. It was Ehrlich who coined the term “Magic Bullet” for this unique action displayed by Methylene Blue. A term still in use today. Methylene Blue has since been used to treat dementia, cancer chemotherapy, malaria, methemoglobinemia, urinary tract infections, cyanide, and carbon monoxide poisoning.545 As a nootropic, Methylene Blue is used to enhance mitochondrial function, increase cerebral blood flow, and acts as an antidepressant. How does Methylene Blue work in the brain?

Methylene Blue boosts brain health and function in several ways. But two in particular stand out. 1. Methylene Blue improves memory. Unlike other nootropics which often work by increasing neurotransmitter synthesis and neural signaling, MB improves memory by increasing brain cell respiration. Or how the brain cell utilizes oxygen. Studies show dramatic increases of cellular oxygen consumption and glucose uptake when using Methylene Blue. MB increases CMRO2 (cerebral metabolic rate) through increased activity in the mitochondrial electron transport chain. Methylene Blue functions as an alternative electron carrier in the electron transport chain in mitochondria. It accepts electrons from NADH and transfers them to cytochrome c.546 Cytochrome complex (cytochrome c) is a component of the electron transport chain in mitochondria. Playing a role in apoptosis and as an antioxidant. Methylene Blue also stimulates glucose metabolism. Taken together, increases in CMRO2 and glucose uptake means that MB elevates oxygen consumption which helps glucose increase ATP production. Increases in ATP production provides more cellular energy for better overall brain function including cognition, mood, and memory. 2. Methylene Blue is an antioxidant. MB has a unique mechanism of action that is fundamentally different from traditional antioxidants. During cellular respiration, the first free radical formed inside a cell is superoxide (O2). Methylene Blue binds to superoxide and reduces it to water. It stops the oxidative cascade at its very beginning. Before it gets a chance to do damage.547 So think of Methylene Blue as having a unique dual property. First, it increases cellular energy production which normally leads to oxidative stress. And second, it eliminates this oxidative stress. Making it a metabolic enhancer and an antioxidant. Researchers tested Methylene Blue in animal models of neurological disease. First, researchers used rotenone (a potent pesticide) which causes severe dopamine depletion in the part of the brain associated with Parkinson’s. Methylene Blue rescued brain cell mitochondria from the damaging effects of this toxin. By donating electrons in the electron transport chain broken by rotenone. Essentially bypassing the broken transport chain with donated electrons as an alternative electron carrier. Methylene Blue also countered cerebral ischemia reperfusion damage. The tissue damage caused when blood supply returns to tissue after a lack of oxygen. As can occur with Traumatic Brain Injury. MB accomplished this by rerouting mitochondrial electron transfer. This means that Methylene Blue dramatically countered the behavioral, neurochemical, and neuropathological impairment found in Parkinson’s disease.548

How things go bad As we live life, our brain chemistry and metabolism changes. ↓ Mitochondrial energy levels decline ↓ Attention, memory and mental agility decline ↓ Tau proteins and amyloid plaques clog the brain ↓ Free radicals damage brain cell mitochondria ↓ Cerebral blood flow declines All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Methylene Blue can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting brain cell mitochondria energy levels. And improving cerebral blood flow. Methylene Blue benefits Low dose Methylene Blue supplementation provides memory enhancing effects in animals and humans. It works as an antidepressant, is anti-aging, helps dementia, Huntington’s, and Alzheimer’s. Methylene Blue increases low blood pressure, improves cognition in healthy people, boosts mitochondrial function, is anti-microbial, can eliminate fear, and even slow skin aging. Methylene Blue boosts acetylcholine Research shows that Methylene Blue is an acetylcholinesterase inhibitor with a preference for muscarinic acetylcholine receptors. Meaning MB prevents the breakdown of acetylcholine and making more available in your brain.549 Methylene Blue is an antidepressant Methylene Blue is a monoamine oxidase inhibitor (MAOI). It inhibits MAO-A more than MAO-B but inhibits both at large doses.550 One study in 1987 showed that 15 mg per day of Methylene Blue was a potent antidepressant in those with severe depression.551 Another study with 31 bipolar disorder patients compared 300 mg per day of Methylene Blue with 15 mg per day. The patients were also on lithium treatment. The study showed that the 300 mg dose of Methylene Blue was a “useful addition to lithium in the longterm treatment of manic-depressive psychosis”. And patients were significantly less depressed.552 Methylene Blue resists Alzheimer’s Disease Alzheimer’s disease and other forms of dementia are associated with a buildup of the protein Tau. Clinical trials show that Methylene Blue inhibits Tau formation. And is under consideration as a

treatment for Alzheimer’s.553 Methylene Blue has an inhibitory action on the cGMP pathway, and affects other molecular events closely related to the progression of Alzheimer’s. Methylene Blue boosts neuron resistance to the formation of amyloid plaques and neurofibrillary tangles. And helps repair impairments in mitochondrial function and cellular metabolism. Research also shows that cholinergic, serotonergic, and glutamatergic systems all play important roles in the development of Alzheimer’s and other cognitive disorders. Methylene Blue provides beneficial effects in mediating these pathways.554 This is particularly significant because most existing treatments for Alzheimer’s can only prevent the disease before it is diagnosed. But Methylene Blue shows promise in delaying the effects of Alzheimer’s and dementia after it is diagnosed. Methylene Blue is anti-aging Research shows that Methylene Blue is an effective anti-aging nootropic. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37-70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium. Methylene Blue is considered a redox agent. Meaning it cycles between oxidized and reduced forms. This cycling by MB helps block oxidant production in brain cell mitochondria.555 Mitochondrial complex IV is the last enzyme in the respiratory electron transport chain of mitochondria. The last step in synthesizing ATP. Your cellular and mitochondrial source of energy. Iron (heme) is an essential element and participates in oxygen transport, DNA synthesis and electron transport. Heme synthesis begins in mitochondria. Every cell requires heme to function properly.556 Senescence or biological aging is the gradual deterioration of cellular function. And is caused by telomere shortening that triggers DNA damage in response to reactive oxygen species, hydrogen peroxide (H2O2), cadmium and other toxins. Methylene Blue helps prevent premature senescence or premature cell death. Methylene Blue improves memory Animal studies have shown that a single low dose of Methylene Blue enhances long-term contextual memory. This type of memory is the conscious recall of the source and circumstances of a specific memory. Other studies show that Methylene Blue in low doses taken after the event helps memory retention of the event. A study done with rats revealed why this works. In this study, rats received 1 mg/kg of MB post-training for 3 days. The researchers then measured cytochrome c oxidation in participants brains. The idea was to determine if an increase in metabolic energy was behind the memory enhancing qualities of MB.

The study found that in the Methylene Blue treated group, brain cytochrome oxidase activity was 70% higher than in the placebo-treated group. The findings suggest that repeated post-training supplementation of Methylene Blue improves memory consolidation. And this memory boost is due to the increased metabolic capacity in brain regions that require more energy during discrimination learning.557 How does Methylene Blue feel? Methylene Blue as a nootropic will likely feel different than any other supplement you’ve ever tried. When reading or studying, once you’re done, you should feel like you fully understand the subject material. And you’ll be able to use what you learned in the future. Methylene Blue seems to facilitate a full understanding of something on the first try. Many neurohackers report the biggest nootropic effect they experience with Methylene Blue is “after the fact learning”. You take in the information. And it’s like your brain sorts through the material. Then stores it in a form you can easily access later. Methylene Blue has this uncanny ability to rewire your brain to forget about any negative associations you have of a situation. And only retains the positive aspects of that memory. Some report that Methylene Blue makes you “feel young again”. It eliminates social anxiety. You’ll feel focused and more confident. Workouts seem easier because you have more energy. Your mitochondria are energized. And you may find that recovery from workouts is easier. Methylene Blue helps eliminate stress. So you have more energy in any situation with a relaxed state of mind. And one recurring theme from many is improved sleep while using Methylene Blue. Methylene Blue Clinical Research Research into Methylene Blue for its therapeutic value goes back to the late 1800’s. But it’s only in the last couple of decades that scientists have been able to decode exactly how Methylene Blue works in the brain. All the way down to the molecular level in mitochondria. A study in 2017 found that Alzheimer’s Disease could be caused by more than the accumulation of amyloid beta in the brain. The scientists looked into the two main components that produce energy in cells. 1. Glycolysis is the mechanism used to convert glucose into a useable form for adenosine triphosphate phosphate (ATP) production in mitochondria. 2. The production of ATP in mitochondria uses oxygen in a process called mitochondrial respiration.

The researchers found that as the brain ages, mitochondrial metabolism deteriorates. Resulting in a reduction in the molecules needed for energy production. And possibly the main culprit behind many neurological diseases including Alzheimer’s and Parkinson’s.558 A study conducted at Children’s Hospital Oakland Research Institute may have found the solution to this mitochondrial energy problem in brain cells. The researchers found that Methylene Blue can prevent or slow the decline of mitochondrial function. One of the key aspects of Alzheimer’s is mitochondrial dysfunction. Specifically complex IV dysfunction. And this is where Methylene Blue steps in. The study found that Methylene Blue enhances complex IV in mitochondria. It increases oxygen consumption. And it reverses premature cell death. The researchers concluded that Methylene Blue may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer’s disease.559 Methylene Blue Improves Memory 26 healthy volunteers aged 22 – 62 participated in a double-blind, randomized, placebo-controlled clinical trial. Purpose of the study was to measure the effects of Methylene Blue on working memory and sustained attention. Study results showed that a single low dose of Methylene Blue resulted in an increase in short-term memory ability. In an area of the brain associated with the senses and visual processing. Timothy Duong, Ph.D., the study author concluded Methylene Blue showed promise “in healthy aging, cognitive impairment, dementia and other conditions that might benefit from drug-induced memory enhancement”.560 Another study published in the American Journal of Psychiatry tested fear extinction (elimination of fear) and contextual memory. Both are forms of long-term memory. In this study, participants received either Methylene Blue or a placebo after being placed in a small dark chamber for a couple of minutes to address their fear. One month later, participants that had used Methylene Blue had less retained fear than those given a placebo. The study authors concluded, “Methylene Blue enhances memory and the retention of fear extinction”.561 Methylene Blue helps Bipolar Disorder Increasing evidence shows that bipolar disorder may be a progressive condition. Dealing with bipolar symptoms long-term results in deterioration of the cortex and less gray matter. A study at Dalhousie University in Halifax compared the effectiveness of lamotrigine (Lamictal®) along with daily supplementation of either 195 mg or 15 mg of Methylene Blue in patients with bipolar disorder.

Patients took a dose (Lamictal and either 195 mg or 15 mg of Methylene Blue) for three months. Then switched to the other dose for 3 months. The team found that bipolar participants had reduced depression and anxiety when taking the higher dose of Methylene Blue compared to when they were on the lower dose. Several bipolar disorder patients in the study chose to continue using Methylene Blue after the study concluded.562 Methylene Blue Recommended Dosage Recommended safe doses based on clinical studies with animals and humans ranges from 0.5 – 4 mg/kg. So a 90 kg (200 lb.) body weight translates to 45 – 360 mg of Methylene Blue. 45 mg of Methylene Blue is a safe starting dose. But 360 mg of MB is much too high in my opinion even if you’re 200 lbs. The bottom line is there is no true recommended dose for Methylene Blue. My recommendation is start with the lowest dose of 0.5 mg/kg and see how you react. Methylene Blue is water-soluble, so you don’t need to take it with a meal, or healthy fat like some nootropics. Methylene Blue has a half-life of about 5 hours. So you can dose twice a day. Methylene Blue is famous for turning urine blue. But for most neurohackers, your urine will only stain blue at doses roughly exceeding 500 mcg. Some recommend preventing blue urine by mixing Methylene Blue with ascorbic acid for 3 hours before taking it. Methylene Blue is also available as a doctor-administered injection for therapeutic use. Typically used to treat diseases like malaria or with anti-cancer therapy. Methylene Blue Side Effects Methylene Blue shows a hormetic dose-response, with opposite effects at low and high doses. In other words, lower doses of Methylene Blue work well as a nootropic. But high doses do not because MB can potentially “steal” electrons away from the electron transport chain. Disrupting the redox balance and acting as a pro-oxidant (instead of an antioxidant).563 Adverse effects of Methylene Blue also come from chemical impurity. Even pharmaceutical (USP) grade Methylene Blue can contain impurities like arsenic, aluminum, cadmium, mercury, and lead. At low doses, these contaminants are not that big of a problem. But higher doses will result in the accumulation of these toxins in your cells. Side effects with Methylene Blue are rare when doses are under 2 mg/kg. But can include stomach pain, chest pain, dizziness, headache, sweating, confusion, high blood pressure, shortness of breath, accelerated heartbeat, tremor, skin turning blue, urine turning blue or green, reduction of red blood cells,

or jaundice (only reported in infants). Monoamine Oxidase (MAOI) inhibition becomes a big problem at around 2 mg/kg of Methylene Blue. So if you are using antidepressants or antianxiety medications that affect serotonin, you should NOT use Methylene Blue. This includes SSRI’s and MAOI’s such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, Zimelidine, bupropion, buspirone, clomipramine, mirtazapine, and venlafaxine. Do not use Methylene Blue if you are pregnant or breast-feeding. Type of Methylene Blue to buy Methylene Blue is sold as a liquid, and in crystalline powder form. Industrial-grade and chemical-grade Methylene Blue is sold as a dye or stain. And can consist of more than 8% - 11% of various contaminants. And should NOT be used as a nootropic. Only pharmaceutical (USP) grade Methylene Blue should be used as a nootropic. Ask for a Certificate of Analysis which should include the amount of contaminants such as arsenic, aluminum, cadmium, mercury, and lead. Nootropics Expert® Recommendation Methylene Blue 0.5 – 4 mg/kg of body weight per day I recommend using Methylene Blue as a nootropic supplement. Your body does not make Methylene Blue on its own. So to get its benefits you must take it as a supplement. Methylene Blue is especially helpful for those dealing with anxiety and depression. Methylene Blue is also particularly useful to students and executives who want to boost cognition, learning and memory. Methylene Blue is a fast-acting nootropic that can also help prevent brain mitochondrial degeneration. Methylene Blue donates electrons in the electron transport chain in your mitochondria. So experienced neurohackers suggest avoiding CoQ-10 or idebenone when using MB because it seems to make Methylene Blue much less effective. Idebenone is an Alzheimer’s drug that has some nootropic benefit. But it works similar to Methylene Blue because it acts as a transporter in the electron transport chain of mitochondria. Competing with Methylene Blue.

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N-Acetyl L-Cysteine N-Acetyl L-Cysteine (NAC) is a powerful antioxidant, can boost mood, lower anxiety, improve memory, and reduce compulsive behavior N-Acetyl L-Cysteine (NAC or N-acetylcysteine) is the N-acetyl derivative of the naturally occurring amino acid L-cysteine. And works primarily by helping restore the body’s natural antioxidant glutathione (γ-glutamylcysteinylglycine; GSH). As the most abundant antioxidant in your body, GSH is responsible for maintaining oxidative balance in each of your cells. Taking glutathione as a nootropic supplement does not adequately restore GSH levels in your brain because it can’t cross the blood-brain barrier. This vastly underrated nootropic, NAC easily penetrates the blood-brain barrier and raises glutathione levels in your brain.564 NAC has been used to treat acetaminophen poisoning for decades.565 Every year there are 56,000 ER visits from Tylenol overdose, resulting in at least 100 deaths.566 NAC provides the glutathione your liver needs to fight off the metabolite NAPQI in Tylenol that does severe liver damage. As a nootropic, NAC helps prevent glutamate toxicity, boosts dopamine, and reduces inflammation, oxidative and free radical damage. L-Cysteine is naturally produced in your body using the amino acid methionine. You can also get LCysteine from eating ricotta and cottage cheese, yogurt, pork, chicken, turkey, duck, wheat germ, granola and oat flakes. But acute stress, illness, or a poor diet can deplete L-Cysteine levels in your body and brain. The quickest and most efficient way to boost levels of L-Cysteine is to supplement with N-Acetyl LCysteine (NAC). NAC regulates the amount of glutamate in your brain. Glutamate is a neurotransmitter that is responsible for sending signals between neurons in the brain. This plays an important role in learning and forming memories. But too much glutamate can be toxic to brain cells. NAC regulates the amount of glutamate and keeps it at safe, healthy levels. NAC influences the amount of dopamine available in your brain. It works to keep dopamine receptors healthy and able to transmit and receive dopamine. These neurotransmitters are crucial for cognitive energy and drive, motor control, feelings of pleasure, and focus. NAC is a precursor to the powerful anti-oxidant glutathione (GSH). GSH is a potent anti-inflammatory, anti-oxidant and free radical scavenger. Your brain is especially vulnerable to inflammation, free radical and oxidative damage. If left unchecked, inflammation, oxidation and free radicals can negatively affect cognition, long-term

potentiation, memory and mood. As a nootropic, NAC can boost glutathione and dopamine levels in your brain. NAC is also used by medical professionals to treat serious cognitive disorders like schizophrenia, bipolar disorder, severe depression and anxiety. How does N-Acetyl L-Cysteine work in the Brain? N-Acetyl L-Cysteine boosts brain health and function in several ways. But two in particular stand out. 1. N-Acetyl L-Cysteine reduces oxidative stress. Oxidative stress results in free radical damage in brain cells. Leading to neurodegeneration and ultimately Alzheimer’s, Parkinson’s and other agerelated neuronal disorders. Proteins and DNA are injured, inflammation, tissue damage and cellular apoptosis (cell death) are the result. And neurohackers are not immune to oxidative stress no matter what your age. Keep this in mind the next time you reach for a Diet Coke. Consumption of the artificial sweetener aspartame induces cortical inflammation and oxidative stress. Researchers did a study with 30 adult male Wistar rats randomly divided into 3 groups. The control group received distilled water. The second group was given aspartame. And the third group was given aspartame and NAC. Oral administration was done in the morning daily for 90 days. The study found that NAC boosted Brain-Derived Neurotrophic Factor (BDNF) levels, blocked the COX-2 and PGE2 inflammatory enzymes, and reduced the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) inflammatory cytokines in the rat cerebral cortex. They also found that NAC replenished glutathione levels. The researchers concluded that NAC prevented neurotoxicity and improved neurological function, suppressed brain inflammation, and oxidative stress response.567 2. N-Acetyl L-Cysteine relieves depression. Major depressive disorder is one of the most common psychiatric disorders. It’s a burden on the individual, family, and the community. And the pharmaceutical companies are making literally billions on selling various anti-depressants. Not treating the cause, producing a host of side effects, and in most cases just ‘dumbing down’ the symptoms. But the pipeline for new anti-depressant drug discovery is at a near stand-still for treating problems like schizophrenia, bipolar disorder, depression and common forms of autism. The good news is that neuroscience continues to work on the problem. And have shown that many of these disorders share inflammation and oxidative stress as part of their disease physiology. Neuroscientists also discovered that associated pathways causing these diseases include a reduction in proteins that stimulate neuron growth (neurotrophins), increased apoptosis (cell death), and reduced energy generation in mitochondria.

It turns out that NAC seems to have multiple effects on all these pathways. NAC reduces the core symptoms of schizophrenia, reduces depression, and reduces cravings for a number of addictions including cocaine, cannabis and tobacco.568 How things go bad As we get older or suffer from chronic illness, our brain and body chemistry and energy metabolism changes. ↓ Oxidative stress in brain cells increase ↓ Free radicals damage neurons ↓ Dopamine receptors stop working ↓ Glutamate toxicity causes cell damage and apoptosis ↓ Brain-Derived Neurotrophic Factor (BDNF) declines ↓ Mitochondria energy declines All of these changes are often attributed to chronic illness, lifestyle choices, and aging. Unchecked, they could lead to neurodegenerative diseases like Parkinson’s, Alzheimer’s, major depression, schizophrenia, OCD, addictions, autism, and a drop in quality of life. N-Acetyl L-Cysteine benefits N-Acetyl L-Cysteine (NAC) is a slightly modified version of the sulfur-containing amino acid LCysteine. When taken as a supplement, NAC replenishes intracellular levels of the natural antioxidant glutathione (GSH). Restoring your cells’ ability to fight damage from reactive oxygen species (ROS). Conventional medicine has used NAC for decades as an inhaled mucous thinner to treat symptoms of cystic fibrosis. NAC is given intravenously (IV) or orally as a treatment for acute acetaminophen poisoning. NAC quickly restores glutathione levels, averting permanent disability or death. The nootropics community has recently discovered NAC as a way to suppress inflammation in the brain. NAC prevents oxidative stress on brain cells, eliminates free radicals, restores Brain-Derived Neurotrophic Factor (BDNF), rejuvenates dopamine receptors, and improves overall cognitive function. NAC can help boost cognition, Long-Term Potentiation for long-term memory formation, short-term and working memory, improve your mood and quell anxiety. How does N-Acetyl L-Cysteine feel? Neurohackers report that supplementing with NAC could be the best nootropic they’ve ever used for their brain and overall health. Comments include: • •

Thinking is clearer (less brain fog) Memory improves

• • • • • • • • • • • • • •

Concentration and attention improves Less anxiety Less depression Less irritable Mood improves (like a ‘clean high’) Symptoms caused by ADHD meds disappear Obsessive Compulsive behavior decreases Sleep quality improves Energy levels increase Weight maintenance is easier Less flu and colds Skin looks better Feel younger Hangovers are less severe

The Research N-Acetyl L-Cysteine increases dopamine Treatments for Parkinson’s Disease are limited to replacing dopamine in the brain. As well as some medications designed to slow down the disease. In 2016, researchers at Thomas Jefferson University showed the oxidative stress in the brain could play a critical role in the progression of Parkinson’s. And this stress lowers levels of glutathione, a compound produced in the brain to counteract oxidative stress. Studies show that N-Acetyl L-Cysteine (NAC) helps reduce oxidative damage to neurons by helping restore the levels of the antioxidant glutathione. In this study, Parkinson’s patients were placed into two groups. The first group received 50 mg/kg NAC intravenously (IV) once per week. And 600 mg of NAC as a supplement twice a day on non-IV days. The second control group received only their standard Parkinson’s treatment. Patients were evaluated at the beginning of the study and again 3 months later. The evaluation consisted of the Unified Parkinson’s Disease Rating Scale (UPDRS), and a SPECT brain scan which measures the amount of dopamine transporter in the brain. Compared to controls, the patients receiving NAC had significant improvements in their scores. One of the study authors said, “We have not previously seen an intervention for Parkinson’s disease have this kind of effect on the brain”. This study demonstrated for the first time the direct effect of NAC on the brain’s dopamine system. NAC has the unique ability to enable dopamine neurons to recover their function.569 N-Acetyl L-Cysteine repairs Traumatic Brain Injury Traumatic brain injury (TBI) is a major public health issue affecting 1.7 million Americans each year.570

TBI can be caused by sports injuries, work accidents, car and motorcycle accidents, falls, and your wife hitting you over the head with a frying pan. Many survivors end up with long-term or even permanent neurocognitive dysfunction. Affecting cognition, motor function (movement) and personality. These disabilities are estimated to cost $9.2 billion in lifetime medical costs and $51.2 billion in productivity losses.571 A major cause of TBI comes from blast exposure on the battlefield. Symptoms are similar to other causes of TBI; dizziness, hearing loss, headache, memory loss, sleep issues, and neurocognitive dysfunction. In a brain subjected to TBI there is glutamate toxicity, free-radical injury to brain cells, electrolyte imbalances, mitochondrial dysfunction, inflammation, apoptosis (cell death) and stroke.572, 573 This double blind, placebo-controlled study was conducted with 81 active duty service members at a forward deployed field hospital in Iraq. All service members in this study were exposed to significant ordinance blast and met the criteria for TBI. Service members were randomly assigned to receive either a placebo or N-Acetyl L-Cysteine (NAC) for 7 days. The resolution after 7 days of all the TBI symptoms listed above was the main outcome measure of this study. The researchers concluded that NAC was a safe pharmaceutical countermeasure of blast-induced TBI. And that further work on long term outcomes and the potential use of NAC in civilian TBI is warranted.574 N-Acetyl L-Cysteine helps alleviate depression Both depression and bipolar disorder are complicated by glutathione depletion. The researchers in this double-blind, multicenter, placebo-controlled study worked with 75 subjects with bipolar disorder. Subjects received 1 gram of NAC twice daily for 24 weeks. NAC treatment caused a significant improvement with depression with those using NAC. The researchers concluded, “NAC appears a safe and effective augmentation strategy for depressive symptoms”. In this case with people suffering from bipolar disorder.575 Dosage Notes N-Acetyl L-Cysteine (NAC) suggested dosage for cognitive benefit is 600 mg 3-times per day. Clinical studies have found that doses up to 2,000 mg per day are safe and effective. And one German study showed the safety of 2,800 mg per day for 3 months in patients with cystic fibrosis.576 NAC has also proven effective against seasonal influenza and flu-like illnesses. One large study of older adults in Italy took 600 mg of NAC twice daily for 6 months. Only 25% of those adults who used NAC experienced flu-like episodes compared to 79% in the placebo group.577

Side Effects N-Acetyl L-Cysteine (NAC) is the N-acetyl form of the naturally occurring amino acid L-Cysteine. NAC is considered non-toxic and very safe. NAC is a slightly modified version of the sulfur-containing amino acid L-Cysteine. So NAC in powder form can have an unpleasant smell. Very rarely can NAC cause nausea, vomiting, diarrhea or constipation. Even more rare are rashes, fever, headache, drowsiness, low blood pressure and liver problems. Side effects can be a result of very high doses of NAC. And if you have a genetic condition called Cystinuria do not use NAC. This rare condition causes stones to form in the kidneys, ureter, and bladder from cysteine. NAC is the N-Acetyl form of Cysteine. Available Forms N-Acetyl L-Cysteine is available in powder, tablet and capsule form. NAC capsules and tablets are usually 600 mg. Some supplement makers add other compounds to their formula. So ensure you read labels carefully. And stick with manufacturers who follow Good Manufacturing Practices (GMP). And are GMPCertified. Nootropics Expert® Recommendation N-Acetyl L-Cysteine (NAC) 600 mg, 3-times per day I highly recommend using N-Acetyl L-Cysteine (NAC) as a nootropic supplement. Your body does synthesize some L-Cysteine from methionine. And you can get L-Cysteine from foods such as dairy, poultry, pork, and some grains and nuts. But most of us don’t get enough N-Acetyl L-Cysteine from our diet. So supplementation will help. And N-Acetyl L-Cysteine is a highly bioavailable form of L-Cysteine. So you should feel its effects faster. NAC is helpful for most neurohackers to improve mood, memory, cognition, and concentration. And NAC helps alleviate brain fog, anxiety, and irritability. NAC is especially helpful to those dealing with Obsessive Compulsive Disorder (OCD). And stacked with ADHD meds, NAC helps alleviate some of the negative side effects associated with stimulants. You can safely use up to 1,800 mg of NAC per day. The usual dose for cognitive improvement is 600 mg dosed 3 times throughout your day.

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N-Acetyl L-Tyrosine N-Acetyl L-Tyrosine (NALT) enhances working memory, executive function, creative flow states, stress reduction, better mood, anti-anxiety and lessens symptoms of ADHD N-Acetyl L-Tyrosine (NALT or NAT) is a highly bio-available form of the amino acid L-Tyrosine. Your brain uses the enzyme tyrosine hydroxylase to convert L-Tyrosine into L-DOPA. Decarboxylation of LDOPA results in synthesis of the neurotransmitter dopamine.578 “Tyrosine” is derived from the Greek word tyros, meaning cheese. It was first discovered by German chemist Justus von Liebig in 1846 in the protein casein from cheese. Tyrosine is considered a non-essential amino acid because it can be synthesized in your body from phenylalanine. Which is found in many high-protein foods such as poultry, fish, dairy, nuts, soy products, lima beans, avocados and bananas. Once converted into dopamine, the enzyme dopamine-beta-hydroxylase converts it into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). This triad of neurotransmitters are collectively referred to as “catecholamines”. N-Acetyl L-Tyrosine can be a highly effective nootropic for boosting cognitive function. And is particularly helpful in maintaining cognitive performance when you’re under practically any kind of stress. Particularly for musicians playing live music like I did for many years. NALT helps maintain optimal cognitive performance during music played above 90 dB’s. N-Acetyl L-Tyrosine works in synergy with stimulants like methylphenidate (i.e. Ritalin).579 Drugs like Ritalin work by blocking the reuptake of the neurotransmitters dopamine, and norepinephrine. And if there’s not enough dopamine available to do the job, Ritalin doesn’t work very well. NALT potentiates increases in extracellular dopamine. NALT also stimulates the production of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) which are crucial in maintaining both overall physical and cognitive health. NALT can boost libido, memory, focus, concentration, mood, offers anti-depressant effects, and improves executive function in those with ADHD. NALT enhances working memory and executive function in the prefrontal cortex. It helps with creative flow states, is fuel for inspiration, cognitive flexibility, and the kind of “convergent thinking” you do in multiple choice exams. N-Acetyl L-Tyrosine (NALT) vs. L-Tyrosine: What’s the Difference? N-Acetyl L-Tyrosine (NALT) is the amino acid L-Tyrosine with an acetyl group added. When you take NALT as a supplement, it breaks down in your kidneys back into L-Tyrosine. So in theory, the two supplements offer the same benefits.

There is some debate in the nootropics community on which is more effective; NALT or plain LTyrosine. NALT is a more soluble form of L-Tyrosine so it should be more bioavailable to your body. However, some studies report that in some cases, a sizeable percentage of supplemental NALT is excreted in urine before it’s converted into L-Tyrosine.580 On a personal note, I haven’t had any issues using NALT as a source of L-Tyrosine. It gives me a dopamine and adrenal boost you’d expect from supplementing with a dopamine precursor. When dealing with ADHD/ADD it’s particularly effective when stacked with ALCAR (Acetyl-LCarnitine). ALCAR easily crosses the blood-brain barrier for boosting acetylcholine levels. And seems to positively influence serotonin levels. And NALT provides my brain with the dopamine it needs to mitigate symptoms of ADHD/ADD. But in the interests of full transparency, I stack this with 20 mg of Ritalin twice a day. Clearly, my brain doesn’t have the capacity to produce enough dopamine on its own. And needs the boost that comes from supplementing with NALT. So like all nootropics, your mileage may vary. Always consider how each nootropic works synergistically with others in your stack. And how they work with any meds you need to take. This is as much art as it is science. And experimentation is key for optimal cognition, and a ‘Limitless’ mindset. How does N-Acetyl L-Tyrosine work in the Brain? N-Acetyl L-Tyrosine boosts brain health and function in several ways. But two in particular stand out. 1. N-Acetyl L-Tyrosine improves memory and cognition under acute stress. Acute stress is defined as short-term stressors that can affect cognition. Examples are extreme heat or cold. Things like cold showers, extreme sports, car accidents, relationship problems, intense movies, business deals gone awry, exams and war zones. In one study done at the University of Bedfordshire in the UK, the effect of L-Tyrosine on cognitive performance was measured before an exercise task. Researchers recruited 8 soccer players. And had them complete a 90-minute soccer simulation performance test in an environmental chamber set at 77 degrees Fahrenheit. The soccer players were given either L-Tyrosine before exercise or a placebo. Cognitive performance was measured before the exercise task. Then again at “half-time”, following half time, and following the entire simulation. The cognitive performance task assessed dual-task and vigilance. The outcome revealed that cognitive vigilance and reaction time among soccer players significantly improved following administration of LTyrosine. Results showed that in warm-weather conditions, L-Tyrosine could enhance cognitive function and

prevent cognitive impairment during exposure to exercise-heat stress.581 2. N-Acetyl L-Tyrosine boosts neurotransmitters. NALT turns into L-Tyrosine once taken as a supplement. It then converts into the neurotransmitter dopamine. Dopamine is used to control movement in your body, is fundamental to memory, attention and problem solving. The unused dopamine can then convert into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Norepinephrine is important for attentiveness, emotions, sleeping, dreaming, and learning. Epinephrine drives your ‘flight-or-flight’ response. It’s what prompts your reaction to dangerous circumstances, emergency situations, or in stressful situations or environments. In one study done in the Netherlands, researchers determined if L-Tyrosine could boost cognitive resources associated with cognitive control. They performed tests designed to measure “working memory” using the N-Back Test. Study participants were asked to engage in a “1-back” condition of easy difficulty and then a 2-back condition of tougher difficulty. Those that used L-Tyrosine demonstrated superior performance in the 2back test, but not the 1-back test. The study authors suggested that L-Tyrosine provides greater cognitive enhancement when cognitive demand increases. The bottom-line; supplementation of L-Tyrosine may help you increase your IQ score due to maximizing catecholamine reserves.582 How things go bad As we get older, our brain and body chemistry and energy metabolism changes. ↓ Dopaminergic neurons are damaged or die ↓ Neurotransmitter levels decline ↓ Thyroid hormones decline ↑ Stress levels increase ↓ Working memory and mood decline All of these changes are often attributed to aging. But could be a result of dietary and lifestyle choices. Unchecked, they could lead to neurodegenerative diseases like Parkinson’s, a drop in quality of life and depression. N-Acetyl L-Tyrosine benefits N-Acetyl L-Tyrosine (NALT) can boost levels of the neurotransmitters dopamine, norepinephrine and epinephrine. And can help a sluggish thyroid produce more T4 and T3. NALT can help boost cognition especially in stressful situations. It helps improve decision making,

‘flow state’ and creativity, cognitive flexibility, and working memory. NALT converts into L-Tyrosine which then converts into L-DOPA to produce dopamine. L-DOPA is also used to make melanin in your body. This conversion process helps in the removal of neurotoxic quinones. And chelates heavy metals like mercury and lead which can accumulate in and damage neurons. The dopamine that is not used by your brain is available to produce norepinephrine (noradrenaline) which is important for attentiveness, emotions, sleeping, dreaming and learning. NALT can be an effective nootropic when stacked with ADHD/ADD meds like Ritalin or Adderall. It helps supply extracellular dopamine needed to improve the effectiveness of stimulants used to boost the uptake of dopamine in your brain. How does N-Acetyl L-Tyrosine feel? Keep in mind that NALT is a precursor to catecholamines. So if you’re not ‘low’ on dopamine, norepinephrine or epinephrine – you may not ‘feel’ anything. Many neurohackers report a lift in mood, better focus, concentration, increased energy, and an overall sense of well-being. NALT can help readjust your motivation levels. It can help lower anxiety levels, especially social anxiety. Supplementing with N-Acetyl L-Tyrosine can help bring your blood pressure down if it’s elevated from a stressful situation or environment. Take it before the stressful event if you can. NALT helps buffer the effects of stimulants like caffeine or amphetamines. It helps potentiate and prolong the effects of Ritalin or Adderall, and reduces the crash. If you’re into athletics or do manual work, you’ll find that supplementing with NALT before a workout or construction job will leave you feeling great afterwards. It helps mitigate many of the effects of acute stress caused by short-term stressors. And NALT helps your body to produce melanin, so you may find it easier to get a tan while at the beach. The Research N-Acetyl L-Tyrosine to treat ADHD Several studies have investigated using L-Tyrosine for the treatment of ADHD. One informal study published in the 1980’s determined that L-Tyrosine resulted in short-term relief from ADHD symptoms. But subjects eventually reached tolerance and a diminished effect. This is important for neurohackers to keep in mind. It seems that NALT on its own can benefit some more than others. Whether you’re treating ADHD, or are perfectly cognitively healthy. I’ve seen more than one report of nootropic users experiencing tolerance after just a week of supplementing with NALT. But most peer-reviewed, published studies show positive results.

One study published in Neuropsychiatric Disease and Treatment in 2011 looked at using amino acid precursors for the treatment of ADHD. Including L-Tyrosine for dopamine, and 5-HTP for serotonin. The study used 85 young people aged 4 – 18 years old, all with a clinical diagnosis of ADHD. They were treated for an initial period of 8 – 10 weeks. Urinary samples to determine serotonin and dopamine levels were collected within the first 4 weeks. If they didn’t reach adequate levels, subjects were moved to higher dosing levels 2 and then 3 until they got relief from symptoms. Researchers found that the dopamine and serotonin precursors yielded similar results to Strattera and Ritalin. And “the amino acid protocol may be equal in efficacy to potent, pharmaceutical ADHD medications”.583 L-Tyrosine reduces blood pressure under stress This study is particularly interesting for its nootropic application. It’s commonly understood that blood pressure rises when we’re under stress. The source of stress doesn’t really matter. Stress up = blood pressure up. A study in Amsterdam showed that L-Tyrosine administration decreased blood pressure about 15 minutes after ingestion. This study involved assessing task performance following acute stress. Acute stress is usually short-term and can be caused by driving, fighting, athletics, martial arts training, war, combat training, CrossFit, cold showers, loud music, intense movies, loud noises, business deals, relationships, school, exams and more. The point is, this study is applicable to every one of us. The study found that L-Tyrosine reduced diastolic blood pressure within 15 minutes of taking the supplement. And blood pressure normalized within 1 hour. This study tells us that L-Tyrosine (and NALT) may promote a decrease in blood pressure caused by stress. And could be used to mitigate the effects of stressful situations if taken prior to the stressful event.584 N-Acetyl L-Tyrosine promotes cognitive flexibility Cognitive flexibility applies to those who can adjust their thinking quickly to adapt to novel situations and stimuli. A high degree of cognitive flexibility is associated with increased fluid intelligence, superior reading and comprehension, and a healthier brain. Recent research (2015) supports the idea that L-Tyrosine (and NALT) promotes cognitive flexibility. In this trial, researchers recruited 22 adults. And setup a double-blind, placebo-controlled study. All subjects were assigned a task switching procedure to measure their flexibility. The results showed that receiving L-Tyrosine supplements increased cognitive flexibility compared to the placebo group. The researchers determined that “L-Tyrosine can facilitate cognitive flexibility by repleting cognitive resources”.585 The team observed that increased cognitive flexibility was likely due to a boost in dopamine

concentrations. They noted that L-Tyrosine enhanced usage of various cognitive resources. And one way to increase your cognitive flexibility would be to start supplementing with N-Acetyl L-Tyrosine. It stands to reason that people who are close-minded, set it their ways, are resistant to change and can’t cope with unexpected stimuli or situations have “cognitive rigidity”. And it’s likely due to suboptimal dopamine levels. Dosage Notes N-Acetyl L-Tyrosine (NALT) suggested dosage for cognitive benefit is 350 – 500 mg twice per day. You may find your body responds to smaller doses. Or even more if your stacking it with stimulants like ADHD meds. Listen to your body and see how you react. Side Effects NALT quickly turns into the non-essential amino acid L-Tyrosine once you take it. So is considered non-toxic and very safe. Most neurohackers don’t have any negative side effects. At higher doses there are reports of stomach issues and migraines. Migraine problems usually happen to those who already suffer from migraines. This may be an indication that your neurotransmitter levels are already optimal, and you don’t need to supplement with NALT. NALT can increase your thyroid hormones. So if you’re hyperthyroid you shouldn’t use NALT. And if you’re taking MAO inhibitors (MAOI’s) like selegiline, Azilect, Marplan or Nardil you should not use NALT. MAOI’s work in your brain and effect neurotransmitters. So using NALT in combination with MAOI’s could throw off the delicate balance of neurotransmitters needed for optimal brain health and cognition. Available Forms N-Acetyl L-Tyrosine is available in powder, capsule, and tablet form. Capsules and tablets are usually 300 – 500 mg. Some pre-made nootropic stacks and workout stacks also include NALT as part of their formula. Ensure you read labels carefully and stick with manufacturers who follow Good Manufacturing Practices (GMP). And are GMP-Certified. Nootropics Expert® Recommendation N-Acetyl L-Tyrosine (NALT) 350 – 500 mg twice per day I recommend using N-Acetyl L-Tyrosine (NALT) as a nootropic supplement. Your body does synthesize some L-Tyrosine from phenylalanine which comes from high-protein foods like chicken, fish, almonds, avocados and bananas. But most of us don’t get enough L-Tyrosine from our diet. So supplementation will help. And N-Acetyl

L-Tyrosine is a highly bioavailable form of L-Tyrosine. So you should feel its effects faster. NALT is helpful for most neurohackers to combat stress and sleep deprivation. It’ll boost dopamine, norepinephrine and epinephrine levels. It’s particularly helpful if you take NALT prior to a stressful situation, workout or physically demanding job. NALT is especially helpful to those dealing with ADHD/ADD. It’s a great compliment to stack with stimulant meds like Ritalin or Adderall. NALT will provide the dopamine your brain needs. It will help smooth out and prolong the effects of stimulant meds. And help prevent the associated crash when they wear off. A good stack for ADHD is using your usual med dose with NALT 500 mg, CDP-Choline 300 mg, and ALCAR 500 mg. You can safely use up to 1,500 mg per day when stacking with ADHD meds. But dosed throughout your day.

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NADH NADH is known for increased alertness, clarity, focus, memory, enhanced mood and energy, and is a potent antioxidant and free radical scavenger NADH (Nicotinamide Adenine Dinucleotide + Hydrogen, or coenzyme 1) is the active coenzyme form of Vitamin B3 (niacin). Discovered early in the 1900’s, it’s also known as Coenzyme 1. Every cell in your body contains NADH. NADH is the primary carrier of electrons in the transfer of food from your diet into energy. This energy is stored as adenosine triphosphate (ATP). ATP which is synthesized within mitochondria in each of your cells. Not enough NADH leads to ATP depletion, which can eventually lead to cell death.586 Studies have shown that supplementing with NADH improves cognitive function, enhances cellular energy, increases endurance, switches ‘off’ aging genes, and extends life span. You get small amounts of NADH by eating meat, poultry, and fish. Vegetables have very low concentrations of NADH. So vegetarians are typically low in NADH. And since NADH is very unstable, much of it is lost through cooking. When you supplement with NADH, cerebral electrical activity increases in areas of your brain used for attention, cognition, focus, memory, concentration, and decision making. How does NADH work in the brain? NADH boosts brain health in several ways. But two in particular stand out. 1. NADH increases the production ATP. NADH carries the electrons needed for the synthesis of ATP. Your brain cell mitochondria create this fuel (ATP) for brain cells to function and stay healthy. By providing the means for ATP synthesis, NADH is involved in cognition, focus, concentration, memory, and processing speed.587 And NADH plays an important role in mediating brain aging and tissue damage. Even decreasing the damage done by strokes.588 In one double-blind, placebo-controlled study researchers did a 3-month trial with Chronic Fatigue Syndrome patients. 86 patients were chosen to receive either 20 mg of NADH daily or a placebo for the first 2-months. Mean age of the participants was 47 years. The study measured the intensity of fatigue, functional performance, mood state, functional impact of fatigue, quality of life, sleep quality, and exercise capacity. Each was measured prior to the study. And then at 30, 60 and 90 days of treatment. The study found that oral administration of NADH resulted in decreased anxiety and maximum heart rate.589 2. NADH increases neurotransmitters. NADH is directly involved in the production of the critical

neurotransmitters dopamine and norepinephrine. Dopamine is usually made inside the neurons that use it. The amino acid tyrosine is first converted to LDOPA through the enzyme tyrosine hydroxylase. L-DOPA is then converted to dopamine. Research shows that tyrosine hydroxylase is the rate-limiting controller of dopamine synthesis. This is seen in Parkinson’s patients where tyrosine hydroxylase is much lower than in healthy people. To complicate things even more, we need to understand what makes tyrosine hydroxylase work. The coenzyme that activates tyrosine hydroxylase is tetrahydrobiopterin (H4BP). And it’s NADH that activates this enzyme, and helps produce H4BP. Researchers in Austria conducted an open label trial with 885 Parkinson’s patients. The study was conducted to try a therapy that might increase the brain’s own dopamine production instead of directly giving the patents L-DOPA. In this study, 415 patients received intravenous (IV) NADH, and 470 patients got an oral dose of NADH. Both groups showed overall good response to treatment including improvements in motor function, walking, pushing, posture, and speech. They also experienced improvements in cognition and mood. The researchers found increased dopamine metabolites in the urine of the patients. Indicating that NADH induced an increase in dopamine production. Most of the Parkinson’s patients were able to reduce and even eliminate their other Parkinson medications.590 How things go bad As we get older, NADH levels decline. And no amount of healthy eating or exercise can stop this decline. ↓ Dopamine and norepinephrine levels decline ↓ Intra-cellular genome communications break down ↓ Energy levels decline All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and Parkinson’s. But even if things haven’t degenerated to such a debilitating level, NADH can help. In fact, it’s required for dopamine synthesis. NADH benefits Research has shown that people with low NADH levels are far more vulnerable to addiction, disease, and other chronic conditions. Low NADH levels can happen at any age. Even at birth. In our Western society, NADH is lost in cooking and food processing. And what little remains is broken down by stomach acid and degraded before it’s absorbed in your digestive tract.

When you take NADH as a supplement, your cells think oxygen levels are normal and start working as if they were younger, undamaged cells. Research from hundreds of studies have shown that NADH will: • • • • • •

Boost energy levels and stamina Reduce fatigue Reduce the possibility of age-related diseases Lower blood pressure Provide protection and energy to your brain Boost cerebral blood flow

How does NADH feel? Using NADH as a nootropic can boost ATP synthesis in your brain. And increase the production of the neurotransmitters dopamine, norepinephrine and serotonin. You should experience a boost in mental and physical energy levels, a better mood, improved cognition and alertness. NADH even helps relieve symptoms related to jet lag. And has been shown to alleviate the symptoms of Chronic Fatigue Syndrome including less brain fog, improved mood and energy, and better cognition. And neurohackers report more endurance during workouts and running. The Research NADH helps reduce Jet Lag Current remedies for jet lag don’t work very well. Chronic commuters have resorted to melatonin, stimulants, sedatives, and phototherapy. And all have produced dismal results in recovering from jet lag. NASA investigated the efficacy of using NADH as a countermeasure for jet lag. NADH increases cellular production of ATP and facilitates dopamine synthesis. So the thinking was NADH could counteract the effects of jet lag on cognitive function and sleepiness. 35 healthy frequent travelers were recruited in this double-blind, placebo-controlled study. Testing was conducted on the West Coast before subjects flew overnight to the East Coast. Subjects were given either 20 mg of sublingual NADH, or a placebo. All underwent testing to assess cognitive function, mood, and sleepiness in the morning and afternoon the day after the red-eye flight. Jet lag resulted in sleepiness for half the participants, and a third of them experienced deterioration of cognitive function. The morning following the flight, subjects experienced lapses of attention, disruptions to working memory, divided attention and visual perceptual speed. Those who received NADH performed significantly better on cognitive and motor tests, showed better performance on other measures, and reported less sleepiness than those who took a placebo.

NASA concluded that, “Stabilized NADH significantly reduced jet lag-induced disruptions of cognitive functioning, was easily administered, and was found to have no adverse side effects”.591 NADH regenerates stem cells in the brain Researcher Hongbo Zhang wanted to understand how the regeneration process deteriorated with age. So he teamed up with colleagues from ETH Zurich, the University of Zurich and universities in Canada and Brazil. Under normal conditions, stem cells react to signals sent by your body, and regenerate damaged organs by producing new specific cells. Fatigue in stem cells is one of the main causes of poor regeneration. Resulting in degeneration in tissues, organs and the brain. The research team set out to revitalize stem cells in the muscles of elderly mice. They gave nicotinamide riboside to 2-year-old mice (which is considered “old” for a mouse). Nicotinamide riboside is a precursor to NADH. The results showed muscular regeneration was much better in mice that received nicotinamide riboside. They lived longer than the mice that didn’t get it. Parallel studies have revealed a comparable effect on stem cells of the brain and skin. This work on the aging process has potential for treating diseases that can affect, and be fatal even in young people, with illnesses like muscular dystrophy. No negative side effects were observed in any of the studies following use of nicotinamide riboside, or stabilized NADH. It appears to boost the functioning of all cells. Including cells that have been damaged.592 NADH decreases anxiety Studies show that NADH may be low in those suffering chronic fatigue syndrome (CFS). So researchers in Spain set out to evaluate the efficacy of supplementing NADH in those with CFS. The research team recruited 86 CFS patients with a mean age of 47 years to take part in a 3-month double-blind, placebo-controlled trial. The patients were given 20 mg of NADH or a placebo for 2 months. The team found that those using NADH experienced a significant decrease in anxiety symptoms. And maximum heart rate dropped.593 NADH reduces symptoms of Chronic Fatigue Chronic Fatigue Syndrome (CFS) has baffled researchers and the medical community for years. Its cause is unknown, and it’s associated with a myriad of symptoms. But the main common denominator in all Chronic Fatigue cases is severe fatigue. And no therapeutic regimen has proven effective for this condition. In this study, 31 patients fulfilling the criteria for CFS were selected to participate. They were given

NADH or other nutritional supplements for 24 months. The 12 patients who received NADH had a dramatic and statistically significant reduction of chronic fatigue symptoms.594 Dosage Notes NADH is a coenzyme, antioxidant form of Vitamin B3 (niacin). It’s a naturally occurring enzyme found in all living cells. And necessary for cellular ATP synthesis and energy production. NADH is available in tablet form as 5, 10 and 20 mg tablets. It’s faster-acting if you can find sublingual tablets. If you’re looking to boost dopamine, stack your NADH with N-Acetyl L-Tyrosine (NALT). Because NADH converts tyrosine to dopamine. Side Effects Your body naturally produces NADH. So it’s non-toxic and very well tolerated. NADH should not produce side effects. Available Forms NADH is highly unstable and for it to remain effective needs to be in a stabilized form. Most neurohackers recommend the patented, stabilized form of NADH that’s made by a German company called ENADA. A couple of major supplement manufacturers license the ENADA brand of NADH. Check the label. Nootropics Expert® Recommendation NADH 10 mg per pay I recommend using NADH as a nootropic supplement. Your body does make some NADH on its own. And from eating meat, poultry and fish. But studies have shown we don’t get an adequate supply of NADH from food sources because most of it is lost in cooking. NADH is particularly helpful for vegetarians because very little NADH is available from vegetables. NADH is especially helpful for those suffering Chronic Fatigue Syndrome. I suggest starting with a dose of 10 mg daily. And NADH is a great compliment to a stack with any nootropic. Do your best to find a stabilized form of NADH like the patented ENAND. For a more effective dopamine boost, stack your NADH with NALT. NADH converts tyrosine to dopamine. You need to provide your brain mitochondria with the tools they need to create ATP which is the energy

each of your brain cells demand. Or neurons start to break down from the inside. Signs that your lacking adequate NADH is brain fog, slow thinking, fatigue and low endurance. Some clinics in the USA and other countries are using NADH therapy as a treatment for addiction, anxiety, depression, chronic stress and post-traumatic stress disorder (PTSD). Intravenous (IV) NADH has been used effectively since the 1960’s for detoxing patients from alcohol, opiates, tranquilizers, and stimulants.595

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Nefiracetam Nefiracetam has been shown to reduce apathy, improve cognition, learning, and long-term memory, reduce anxiety, depression and stress, boost nerve growth factor, and is neuroprotective Nefiracetam (DM-9384, N-(2, 6-dimethylphenyl)-2-(2-oxopyrrolidine-1-yl)-acetamide) is in the racetam-family of nootropic compounds. It is a fat-soluble nootropic. Nefiracetam was developed by Daiichi Seiyaku in the 1990’s as a treatment for cerebrovascular disorders. In 1999, Nefiracetam was in phase II clinical trials in the USA for treatment of cognition problems as a consequence of stroke, and Alzheimer’s type dementia.596 It is similar in structure to Piracetam with a phenyl group and two methyl groups added to the amine of Piracetam. Nefiracetam, like all racetam nootropics, has a pyrrolidone nucleus at its core. The structure of Nefiracetam is similar to Aniracetam. And Nefiracetam is a cholinergic compound, meaning it affects acetylcholine levels in the brain. Nefiracetam is used as a prescription drug in Japan. And as a supplement in the United States. One of the most recent synthetic nootropic compounds, it is known as a cognitive enhancer. And is known for its anxiolytic, or anti-anxiety effects. Nefiracetam is considered to be much more potent than Piracetam. As a nootropic, it helps increase attention span, alertness, cognition, learning and boosts memory. Nefiracetam vs. Piracetam: What’s the Difference? Japan-based pharmaceutical company Daiichi Seiyaku developed Nefiracetam in the late 1990’s as a derivative of Piracetam. Nefiracetam is fat-soluble while Piracetam is water-soluble. Fat-soluble molecules cross the bloodbrain barrier more easily than water-soluble molecules. Both Nefiracetam and Piracetam are cognitive enhancers. And both have neuroprotective qualities. Both racetams are able to improve learning and memory. And both are able to prevent brain damage. Nefiracetam has additional benefits not shared with Piracetam. Nefiracetam can reduce anxiety and depression. And exhibits several other memory enhancing qualities over Piracetam. Nefiracetam increases the amount of time calcium channels in neurons remain open. Tied to protein kinase A (PKA) and the Gi alpha subunit (Gi/o protein), signaling is enhanced in the neuroreceptor independent of the synapse. This calcium channel pathway is critical for long-term potentiation (LTP) and the formation of long-term memories.597 Nefiracetam also potentiates protein kinase C alpha (PKCα) which is involved in long-term potentiation (LTP).598 PKCα is dependent on glutamate signaling.

And Nefiracetam activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) which is critical in memory formation. Again dependent on glutamate signaling.599 Finally, Nefiracetam potentiates acetylcholine receptors in the hippocampus which encourages glutamate release and LPT. Piracetam does not share this memory enhancing quality.600 The bottom-line is Nefiracetam seems to be a much more potent memory enhancer that the original nootropic Piracetam. How does Nefiracetam work in the Brain? Nefiracetam boosts brain health and function in several ways. But two in particular stand out. 1. Nefiracetam enhances memory. In several studies and clinical trials, researchers have noted Nefiracetam’s anti-amnesia effects. And they’ve arrived at this observation by noting Nefiracetam interacting with individual acetylcholine receptors in the brain. One study conducted at the Albert Einstein Healthcare Network in Philadelphia worked with older rabbits. Researchers use a technique called the “nictitating membrane (NM)/eyeblink response” in rabbits which is used in the lab to study age-related memory disorders. In this case, the team used Nefiracetam to study its effect on retention and relearning. The scientists administered 5, 10 or 15 mg/kg of Nefiracetam to 34 “retired” rabbits over 15 days. And then tested retention and relearning 1, 5 and 12-weeks post-training. The researchers found that the effect of Nefiracetam on the ability of older rabbits to relearn was apparent up to 5 weeks after using Nefiracetam. In other words, Nefiracetam had a significant effect on memory long after the rabbits stopped using it. The researchers concluded that Nefiracetam likely has an even greater effect on memory the longer you use it.601 This testing model is dependent on cholinergic (acetylcholine) firing in the brain.602 2. Nefiracetam alleviates depression. Nefiracetam enhances signaling of GABA on GABAa receptors when GABA is too low. And has a suppressive effect when GABA is too high.603 Leading to stabilized mood and sociability. No mood swings! Nefiracetam also provides an antidepressant effect by activating the enzyme Ca2+/calmodulindependent protein kinase II (CaMKII). Scientists in Japan worked with mice with depressive-like behaviors. The mice were given 1 mg/kg per day of Nefiracetam. And noticed antidepressant effects within a day of supplementation.604 Note that this antidepressant effect takes a completely different approach to controlling depression compared to SSRI’s. Prescription antidepressants like SSRI’s mess with serotonin levels in your brain to control depression. And unlike Nefiracetam, come with a host of side effects. Also note that the CaMKII enzyme is associated with a boost in long-term memory formation.

How things go bad Glutamate is an excitatory relative of GABA. While GABA has a calming effect, glutamate stimulates. Glutamate is the most common neurotransmitter in the central nervous system. Glutamate can be toxic to neurons. And too much of it in your brain can kill brain cells. Lou Gehrig’s Disease for example, is caused by excess glutamate. But glutamate is a pivotal neurotransmitter in the brain. It links the brain circuits involved in memory, learning and perception. ↑ Too much glutamate can kill neurons ↑ Too much GABA can cause brain damage ↓ Too little GABA can cause depression ↓ Too little glutamate can cause problems with memory, learning and perception ↓ Acetylcholine levels decline All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Nefiracetam can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting acetylcholine and controlling glutamate and GABA in the brain. Nefiracetam benefits Nefiracetam modulates GABA (gamma aminobutyric acid) in your brain. GABA is the primary inhibitory neurotransmitter in the brain. Its role is to keep glutamate, the primary excitatory neurotransmitter from overwhelming your brain. And causing damage. When GABA levels are too low, you experience anxiety, insomnia, poor mood and restlessness. Left unchecked it can lead to neurodegenerative disease and a very poor quality of life. But when GABA is too high, you have a toxic environment in your brain. Causing damage to neurons and other areas of your brain. Nefiracetam modulates GABA levels, keeping them steady for a healthy brain. And improved long-term memory. Nefiracetam contributes to learning by enhancing long-term potentiation (LTP). Enhancing NMDAdependent LTP at low concentrations and AMPA dependent LTP at higher concentrations.605 Nefiracetam combined with choline boosts the production of the crucial neurotransmitter acetylcholine. Improving memory, recall and focus. Nefiracetam is fat-soluble and quickly enters your brain after you take it. Once in your brain, it boosts signal transmission, and protects neurons. Nefiracetam boosts acetylcholine so you should add a good choline source. Try Alpha GPC or CDP-

Choline with Nefiracetam. And give your brain the choline it needs. How does Nefiracetam feel? Several studies have noted that short-term or one-time use of Nefiracetam doesn’t do much. Supplementing Nefiracetam every day for 7 days or more is needed to experience the full benefit of this nootropic. Nootropics users report: • •

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Nefiracetam as a study aid. Nefiracetam provides calm focus, recall and cognition for many neurohackers. It improves attention span, motivation, and alleviates apathy and mental fatigue. Increased visual acuity. The visual effects of Nefiracetam feel like your brain is processing a broader spectrum of what’s in your visual range. Nature and your surroundings look more vibrant and beautiful. Mood. Many users report a calm focus and being able to articulate thoughts, and improved speaking ability. Language and your vocabulary seem to flow effortlessly. Thoughts and ideas come with less effort.

Some experienced users of Aniracetam say they prefer Nefiracetam. You may recall that the chemical structure of Nefiracetam is very similar to Aniracetam. And the clinical studies support its superior ability to affect memory. You should be able to experience the full effects of Nefiracetam within 7 days of starting to supplement with it. It’s fat-soluble so it’s digested and enters your cells quickly. The Research Nefiracetam was developed by a company in Japan in the late 1990’s. As a result, the majority of the published research available in the Western directories was conducted in Japan. And most of it on rats and mice. Clinical trials for Nefiracetam have been conducted in China and the USA for use in treating Alzheimer’s Disease. So far, no large pharmaceutical company in the USA has formulated a prescription drug version of Nefiracetam to my knowledge. Nefiracetam as an Antidepressant Researchers at The University of Iowa in the USA conducted a double-blind, placebo-controlled trial with 159 stroke patients with major depression. Patients received 600 mg or 900 mg of Nefiracetam or a placebo within 10 days to 3 months after their stroke. The trial ran for 12 weeks with patients evaluated at 4, 9 and 12 weeks of the trial. The study concluded that Nefiracetam produced a significant improvement in the most severely depressed patients.606 Nefiracetam Improves Learning & Memory Much of the research on Nefiracetam has been done with learning and memory in mind.

One study conducted in Ireland used Nefiracetam with rats. Scopolamine, a memory inhibitor, was given to the rats while they were in training. Scopolamine is used to purposely inhibit memory. When the researchers gave the memory-deprived rats Nefiracetam, task recall improved and significantly improved memory deficits.607 Another Irish study with rats showed 40-days of Nefiracetam supplementation induced Nerve Growth Factor and neurogenesis. Proving that Nefiracetam could facilitate long-term memory consolidation.608 Nefiracetam Reduces Apathy Supplementing with Nefiracetam is reported by many neurohackers to boost motivation and a “get it done” attitude. Which is the opposite of ‘apathy’. Stroke patients who suffer depression commonly experience apathy. Researchers at The University of Iowa conducted a study with 137 stroke patients with major depression. 70 of which also met published diagnostic criteria for apathy. The patients were assigned a placebo, or 600 mg or 900 mg of Nefiracetam per day for 4 weeks. Patients who used 900 mg of Nefiracetam had a significantly greater improvement in Apathy Scale scores compared to the other two groups. Conclusion: Nefiracetam reduces apathy. Dosage Notes Recommended Nefiracetam dosage is 100 mg to 900 mg per day. Taken in divided doses. One Nefiracetam dose in the morning, and one in the early afternoon. Nefiracetam is sold in tablet, capsule and powder form. Tablets and capsules are usually 400 - 600 mg each. Since Nefiracetam is a fat-soluble nootropic, you should take it with a meal containing healthy fats. Or with a tablespoon of extra virgin, expeller cold-pressed coconut or olive oil. Or other similar healthy fat to ensure quick absorption. Nefiracetam also boosts acetylcholine (ACh) activity in your brain. To avoid a “racetam headache” make sure to stack Nefiracetam with a good choline source like CDP-Choline or Alpha GPC. Note that most studies suggest, and many neurohackers report that it will take at least 7 days of daily dosing of Nefiracetam to experience the full benefit of this nootropic. Side Effects Nefiracetam non-toxic. So is considered well-tolerated and safe. Side effects are rare but can include anxiety, fatigue, headaches, nervousness and nausea. Side effects are often a result of unusually high doses of the nootropic. Headaches from using Nefiracetam typically happen when you forget to combine it with a good choline supplement. Headaches are often a symptom of a choline deficit in your brain.

Nearly all of the toxicity studies on Nefiracetam have been done on animals. And prolonged usage of this nootropic have shown no toxic effects at recommended doses. One study with male Beagle dogs reported a reduction in testicular testosterone after a single treatment of Nefiracetam. But before you write this nootropic off, note that the dose was a ridiculous 180 or 300 mg/kg dose.609 That’s the equivalent of 16 or 27 grams of Nefiracetam for a 200 lb. male human. And dogs happen to metabolize Nefiracetam differently than humans and primates. The metabolite M18 in dogs seems to be the culprit. And is not found in humans or monkeys.610 I’m not going to belabor this point. But to say that Nefiracetam is safe and non-toxic if used at recommended doses. As long as you’re not a Beagle. Just don’t give it to your dog! Available Forms Nefiracetam is sold in tablet, capsule, and powder form. Tablets and capsules are usually 400 - 600 mg each. Nootropics Expert® Recommendation Nefiracetam 100 - 900 mg per day I recommend using Nefiracetam as a nootropic supplement. Your body does not make Nefiracetam on its own. So to get its benefits you must take it as a supplement. Nefiracetam is especially helpful for those suffering from apathy, loss of motivation and memory loss. Studies show it helps stop and reverse the symptoms associated with apathy. And this nootropic helps boost the activity of GABA, glutamate and acetylcholine in your brain. All involved in long-term potentiation and formation of long-term memory. Nefiracetam is also particularly useful to students and executives who want to boost cognition, learning and especially long-term memory. Neurohackers with experience using Nefiracetam show it helps boost study scores, work flow, learning and memory. You should use Nefiracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain. You can safely boost daily intake of Nefiracetam to 1,200 mg if needed. All daily dosing of Nefiracetam should be in divided doses if above 200 mg per day. One dose in the morning and another early afternoon.

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Nicotine Nicotine has been shown to improve concentration, focus, mental clarity, motivation, memory, and reduce mood swings and anxiety Nicotine (3-(1-Methyl-2-pyrrolidinyl) pyridine) is an alkaloid found in tobacco leaves. But nicotine is also present in very small amounts in plants from the Solanaceae or nightshade family including potatoes, tomatoes and eggplant.611 Nicotine has been used by humans for its psychoactive (nootropic) properties for thousands of years. But it is only in the last several decades that nicotine’s mechanism of action in the brain has been revealed. Nicotine works primarily by upregulating nicotinic acetylcholine receptors (nAChR) in the brain. Stimulating and regulating the release of a host of neurotransmitters including serotonin, dopamine and norepinephrine. Increasing neural signaling of neurotransmitters and boosting alertness, cognition and memory. Studies have shown however that this upregulation of nAChR is dose dependent. And too much nicotine desensitizes these receptors.612 So low doses of nicotine are key in using nicotine as a nootropic for cognitive benefit. Since we’re investigating nicotine as a nootropic here, it’s important to point out that I am not encouraging smoking. Smoking tobacco has been shown to increase cognition. But the harmful effects of tobacco have been proven extensively.613 Including this study that showed life-time smokers have less gray matter in the prefrontal cortex compared to non-smokers. Affecting the brain’s reward, impulse control and decision-making circuits.614 New drugs derived from nicotine and research on nicotinic acetylcholine receptors are in clinical trials for Alzheimer’s, ADHD, anger management, anxiety, depression, schizophrenia, Tourette Syndrome and wound healing.615 As a nootropic, we’re talking about using a nicotine lozenge or gum for cognitive enhancement. Again, I’m NOT talking about smoking tobacco. Smoking is the cause of 5 – 6 million deaths per year. Affecting 18 different organs in your body. But it’s not the nicotine in tobacco that kills. The biggest issue with using nicotine as a nootropic is that it can be addictive. But it’s not the nicotine that causes cancer. Nicotine however could be a “tumor promoter” (if you already have tumors in your body). Nicotine binds specifically to the nicotinic acetylcholine receptor (nAChR) in your brain. And it deregulates essential processes like regulation of cell proliferation, apoptosis (programmed cell death), migration, invasion, angiogenesis, inflammation and cell-mediated immunity of stem cells, adult tissues

and cancer cells.616 As a nootropic, nicotine works in smalls doses (i.e. 1-2 mg) used occasionally when you need that cognitive boost. If you have cancer or a tendency to tumor growth you should avoid using nicotine as a nootropic. How does Nicotine work in the Brain? Nicotine boosts brain health and function in several ways. But two in particular stand out. 1. Nicotine boosts memory. Nicotine binds to presynaptic nicotinic acetylcholine receptors in the brain. And boosts the release of acetylcholine (ACh), dopamine, serotonin, and glutamate.617 Neurotransmitters known to be involved in cognitive processes. Problems with cholinergic signaling has been implicated in neurologic disorders including schizophrenia, ADHD and addiction. And much of the study of nicotine’s effects on cognition has been done looking for treatments for these disorders.618 The National Institute of Drug Abuse conducted a meta-analysis of 41 double-blind, placebo-controlled studies between 1994 and 2008. The analysis found significant positive effects of nicotine on fine motor performance, alertness, attention and accuracy, response time, short-term and working memory.619 2. Nicotine improves attention. Attention deficits are often associated with those dealing with ADHD. The inability to focus can cause all kinds of problems both in relationships, and on the job. Nicotine has been shown to improve attentiveness in smokers. And helps alleviate attention deficits in Alzheimer’s Disease, schizophrenics, and adults with ADHD. A double-blind study conducted at Duke University Medical Center used nicotine patches to see if it would improve attentiveness in non-smoking adults without attention deficits. Subjects received 7 mg of nicotine per day using a transdermal patch for a 4 ½ hour morning session. Nicotine significantly decreased the number of omission errors during testing. And in this study, decreased the variance in “hit reaction time” which is used a measure of attentiveness. The study showed that nicotine reduced attention deficit, and even improved attentiveness in normal adult non-smokers.620 How things go bad As we get older, our brain chemistry and energy metabolism changes.621 ↓ Acetylcholine signaling in the brain declines ↓ Dopamine, norepinephrine, epinephrine and serotonin levels decline ↓ Alertness, attention and memory declines

↑ Anxiety, depression and stress increases All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. Nicotine benefits Nicotine boosts levels of dopamine, epinephrine (adrenaline), norepinephrine and serotonin. And stimulates the growth of new blood vessels. Even increasing the number of red blood cells. Nicotine rapidly crosses the blood-brain barrier. Within 20 seconds of putting a nicotine lozenge under your tongue. It has the fastest action of any nootropic we review on Nootropics Expert, and in this book. Alpha brain waves increase with nicotine which provides a relaxed state associated with super-learning, flow states and joy.622 Nicotine stimulates electrical and neurotransmitter activity throughout your brain. Helping alertness, mood, motivation, selective attention, sustained attention, and decreases distraction.623 Nicotine helps pre-attentional processing which is your ability to detect information. It brings you down when you’re up. And it brings you up when you’re down. And it helps you cope with stress and anxiety. And nicotine improves short-, long-, and working memory processes.624 How does Nicotine feel? Neurohackers report nicotine improves mental clarity and motivation. Mood swings are minimized and less anxiety. Concentration and focus significantly get a boost with nicotine as a nootropic. All forms of memory get a boost with nicotine. Short and long-term memory. And working memory. Nicotine induces long-term potentiation in the hippocampus which is the basis for the neuroplasticity that helps encode long-term memory.625 The key with nicotine is to use low doses. And only use it occasionally. Too much nicotine desensitizes the alpha-7 nicotinic acetylcholine receptor. So tolerance is an issue. But your receptors recover fairly quickly if you give them a break for a day. The Research Much of the research conducted with nicotine was done with cigarette smokers. The studies were to determine the effects of abstinence (quitting smoking) on cognition. Or funded by tobacco companies out to prove smoking was good for you (i.e. improved cognition). So keep an open mind when reviewing these studies. My intent is certainly not to encourage smoking. But to show the effects of nicotine regardless of the delivery system to the human brain. Nicotine boosts IQ

Researchers in New Zealand conducted a trial with 10 women and 6 men ranging in age from 18 – 32 years. All participants were smokers and were instructed not to smoke during the 2-hour period prior to the experiment. Each subject completed the even and odd numbers of the Raven’s Advanced Progressive Matrices (APM) test in two sessions. APM is a test to measure intelligence (IQ). In each of 2 experimental sessions, subjects were given 20 minutes to complete the assigned half of the APM. Before beginning the test, subjects took 6 puffs of a medium (0.8 mg) cigarette every 20 seconds. After 10 minutes, subjects were prompted to take 2 additional puffs. Results of the experiment showed that APM scores were significantly higher in the smoking session compared to the non-smoking session. Suggesting that nicotine acts to enhance intelligence.626 Another study at the University of Colorado may explain part of this boost in IQ. Nicotine was found to increase the efficiency of neural communication between areas of the brain involved in cognition. And even the rest of the brain.627 Nicotine improves typing speed Researchers conducted 5 experiments to study the effects of using 2 mg of nicotine on keyboard typing speed. In study after study nicotine produced a reliably consistent increase in typing speed.628 Nicotine will also improve and increase the speed of your handwriting. Scientists in Germany noted that nicotine has consistently been shown to improve psychomotor performance. So they recruited 38 smokers and 38 non-smokers to participate in a study. Both groups received gum containing 0, 2 or 4 mg of nicotine. And their handwriting performance was assessed after they chewed the nicotine gum. Subjects were asked to perform a simple writing task. Movement time, velocity and acceleration of handwriting movements were measured. Nicotine reduced movement times, increased writing velocity and more fluid handwriting movements were observed. The results suggested that nicotine can enhance psychomotor performance to a significant degree in a real-lie motor task.629 Nicotine boosts memory Nicotine has been shown to improve short-term and working memory in several studies. In this study conducted in the UK, researchers recruited 60 smokers and 60 non-smokers in a double-blind procedure. Half of the subjects chewed nicotine gum and the other half chewed a placebo prior to performing a memory task. Results showed that nicotine significantly improves short-term memory.630 Nicotine for the treatment of ADHD Several studies have shown the benefits of nicotine in treating the symptoms of ADHD. Focusing and memory break down in those of us with ADHD and ADD. And treatment with Ritalin, Adderall or other stimulants often corrects this inattentiveness and memory impairment. But it does nothing for the

accompanying depression and anxiety. And this is the reason why many Adult ADHD sufferers smoke. This study showed that using a nicotine patch not only helped decrease anxiety and depression symptoms of ADHD. It also helped smokers stop using tobacco products while taking care of their ADHD symptoms.631 In this study, nicotine was compared to the effects Ritalin and or a placebo had in treating ADHD. Nicotine improved performance and reduced errors. It decreased depression, and decreased overall severity of ADHD symptoms.632 Another double-blind, placebo-controlled trial worked with 6 smokers and 11 nonsmokers with Adult ADHD. Nicotine decreased ADHD symptoms, increased vigor, and improved reaction time.633 Dosage Notes Nicotine as a nootropic is dosed at 1 – 2 mg on an as needed basis. Nicotine gum typically comes in 2 – 4 mg. You can cut a 4 mg piece of gum in half for a 2 mg dose. Gum releases the nicotine dose over the course of 20 – 30 minutes. The problem with nicotine gum is aspartame along with other unhealthy sweeteners. Nicotine patches come in varying strengths and usually contain more nicotine than gum or lozenges. Neurohackers (contrary to package warnings) cut the patch to size depending on the dose they want to use. My preferred method is nicotine lozenges. The mini-lozenges are best because they’re not full of toxic chemicals like the larger lozenges. The 2 mg mini-lozenge cut in half provides a nice cognitive boost in 10 - 20 minutes. Side Effects Nicotine is addictive primarily because it boosts levels of dopamine in your brain.634 Not nearly as addictive as smoking tobacco but addictive nonetheless. Nicotine can cause increased heart rate, dizziness, cough, sneezing, sinus problems, upset stomach, constipation, and headaches. Nicotine does not “cause” cancer. But may be a tumor promoter. So if you had or currently have cancer you should avoid nicotine. If you are dealing with a gut infection of H pylori bacteria, you should not use nicotine until you get this problem under control. Available Forms Nicotine as a nootropic comes in gum, inhalers, lozenges, and transdermal patches. See “Dosage Notes” for specific dosing instructions.

Mini-lozenges are the safest and best form for nootropic use. Nicotine spray is a newer option you may want to try. You get a 1 mg dose for each spray under your tongue (sublingually). Great for a quick cognitive boost and burst of energy. There’s about 100 sprays in each container. Of course there is also smoking and chewing tobacco for your nicotine dose which I DO NOT recommend. Vaping is another option. But it can come with a host of potential issues if you’re not familiar with vaping. The safest option is rebuildable coils using stainless steel wire and organic cotton with vegetable glycerin as your nicotine base. And keeping the temperature and wattage low. Nootropics Expert® Recommendation Nicotine 1 - 2 mg per dose I recommend using Nicotine as a nootropic supplement. Your body does not make nicotine on its own. So if you are going to supplement with nicotine, you must take it as a supplement. Nicotine is helpful for those dealing with short-, long- and working memory problems, low energy, depression or anxiety. Nicotine is especially helpful for dealing with the symptoms of Adult ADD or ADHD. Nicotine can help relieve most of the symptoms of ADHD. And is a good compliment to your existing ADHD meds. While nicotine is a powerful cognitive enhancer, it is also addictive and can lead to tolerance and withdrawal symptoms in some people. So caution is advised. And if you’re prone to addiction please stay away from nicotine. As neurohackers, we have great acetylcholine agonists available to us if you don’t want to experiment with nicotine. Most of the racetams will boost acetylcholine use in the brain. I suggest starting with a dose of ½ - 1 mg of nicotine in mini-lozenge or spray form. Nicotine will compliment nearly everything in your current nootropic stack. There is no benefit to dosing more than 2 mg of nicotine for cognitive benefit. And too avoid addiction and tolerance I suggest only using nicotine occasionally.

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Noopept Noopept is known for boosting cognition, memory, learning, perception, logical thinking and mood Noopept (n-phenylacetyl-l-prolylglycine ethyl ester or GVS-111) is often included in the racetamfamily of nootropic compounds. But is not a true “racetam” because it does not have a 2-oxo-pyrrolidine nucleus. Noopept was developed in Russia where it is called Ноопепт or GVS-111. Russian-based pharmaceutical company JSC LEKKO Pharmaceuticals synthesized Noopept in 1996 based off the endogenous neuropeptide cycloprolylglycine (CPG). Researchers in Moscow found Noopept similar to piracetam in not only it’s nootropic effect, but also anxiolytic activity.635 Noopept is a water-soluble ampakine nootropic. AMPA (α-amino-3-hydroxy-5-methyl-4isoxazolepropionic) refers to one of three glutamate receptors in your brain.636 Noopept could also be considered a Cholinergic compound because it affects acetylcholine levels in the brain. Noopept does not appear in blood samples when taken as a supplement. Instead it elevates concentrations of cycloprolylglycine (CPG) in the brain. CPG is a dipeptide consisting of proline and glycine which acts as a modulator of acetylcholine transmission and AMPA receptor function.637 One of the newer synthetic nootropic compounds, Noopept is known as a cognitive enhancer. And is known for its anxiolytic, or anti-anxiety effects. Noopept is considered to be up to 1000-times more potent than Piracetam. As an ampakine nootropic, it helps increase attention span, alertness and boosts all three levels of memory; memory formation, retention and recall. Ampakines tend to have a stimulant effect. But do not produce the same stimulant side effects as Ritalin or coffee from prolonged use. Noopept vs. Piracetam: What’s the Difference? Russian-based pharmaceutical company JSC LEKKO Pharmaceuticals developed Noopept in the late 1990’s as a peptide analogue of the original nootropic Piracetam.638 Noopept and Piracetam are both water-soluble. And both Noopept and Piracetam are cognitive enhancers. Both have neuroprotective and anxiolytic (anti-anxiety) qualities.639 Both racetams are able to improve learning and memory. And both are able to repair brain damage. But Noopept has additional benefits not shared with Piracetam. First, the effective dose of Noopept

compared to Piracetam is 1,000-times lower. A typical dose of Noopept is 10 – 30 mg while Piracetam is often dosed up to 3 or 4,000 mg. Second, Piracetam facilitates only the early stages of the memory process. On the other hand, Noopept influences memory consolidation AND retrieval steps as well. So Noopept helps you develop the memory, retain the memory, and then recall what you have stored in memory.640 Noopept also has additional selective anxiolytic (anti-anxiety) action. Researchers believe this is due in part to Noopept’s antioxidant effect, anti-inflammatory action, and the ability to prevent the neurotoxic effect of too much calcium and glutamate. How does Noopept work in the Brain? Noopept boosts brain health and function in several ways. But two in particular stand out. 1. Noopept modulates AMPA and NMDA receptors and acetylcholine (ACh) transmission. Noopept boosts the level of cycloprolylglycine (CPG) in the brain. CPG is a dipeptide consisting of proline and glycine which acts as a modulator of acetylcholine transmission, and AMPA and NMDA receptor function. When brain cells are starved of oxygen, glutamate which is your brain’s primary excitatory neurotransmitter, does not work efficiently with neuroreceptors. The result can be a toxic buildup of glutamate within brain cells. Causing neuron damage and ultimately, neuron death. Noopept modulates neuroreceptor function keeping glutamate transmission at normal levels. Protecting neurons and other brain cells from glutamate damage. Noopept has also been shown to modulate acetylcholine flow in your brain. Restoring the harmony of glutamate and acetylcholine function not only protects your brain from damage. It can boost cognition, memory, learning, recall, mood and relieve anxiety. 2. Noopept increases Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and mRNA. NGF and BDNF are directly related to neuroplasticity. This ability to repair and even grow new brain cells can have profound implications. Particularly with someone with neurodegenerative brain damage like Parkinson’s or Alzheimer’s. And even affecting Long-Term Potentiation needed for long-term memory development. mRNA affects the expression of genes and intracellular communication in brain cells. This ongoing brain signaling and gene expression within brain cells is required for healthy cognition. One study conducted in Moscow showed long-term use of Noopept boosted NGF, BDNF and mRNA. The animal subjects in this study showed no sign of tolerance. And long-term use of Noopept even potentiated the neurotrophic effect.641 How things go bad Glutamate is an excitatory relative of GABA. While GABA has a calming effect, glutamate stimulates.

Glutamate is the most common neurotransmitter in the central nervous system. But glutamate can be toxic to neurons. And too much of it in your brain can kill brain cells. Lou Gehrig’s Disease for example, is caused by excess glutamate. But glutamate is a pivotal neurotransmitter in the brain. It links the brain circuits involved in memory, learning and perception. ↑ Too much glutamate can kill neurons ↓ Too little glutamate can cause problems with memory, learning and perception ↓ Acetylcholine levels decline ↓ Nerve Growth Factor declines ↓ Brain-Derived Neurotrophic Factor declines All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Noopept can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting NGF, BDNF and acetylcholine, and controlling glutamate in the brain. Noopept benefits Noopept modulates AMPA and NDMA receptors. AMPA receptors are associated with how glutamate and calcium is used in your brain. With Noopept, it’s more of a neuroprotective role. Similar to the AMPA receptor, the NMDA receptor is also associated with glutamate and calcium use in your brain. They work together to modulate how neurons use glutamate. Noopept modulates levels of glutamate within and between neurons. It prevents glutamate toxicity and influences Long-Term Potentiation (LTP). LTP is associated with neuroplasticity that allows long-term memories to form. There is clinical evidence that Noopept boosts communication and neuron signaling. By boosting Alpha and Beta brain wave activity. You become calmer and more creative. It’s easier to go into a flow state. And you are prone to making innovative and resourceful decisions. Noopept produces an anxiolytic (anti-anxiety) effect. It stimulates dopamine receptors (D2 and D3) and acetylcholine nicotinic receptors. And Noopept also seems to modulate some serotonin receptors. All contributing to a better mood and less anxiety. Noopept has been shown in the lab to boost Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). NGF and BDNF are both involved in neuroplasticity, and the repair and replacement of damaged brain cells. Resulting in overall better brain health, memory and cognition.642 Noopept is water-soluble and quickly enters your brain after you take it. Once in your brain, it boosts

signal transmission, and protects neurons. How does Noopept feel? Nootropics users report: • •

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Noopept as a study aid. On its own, Noopept increases focus and attention for many neurohackers. Mental arithmetic and grasping difficult concepts is easier. Increased verbal fluidity. Your conversation skills could increase with Noopept. Vocabulary comes easier. Being able to focus contributes to a more balanced dialogue. Neurohackers report being more outgoing, friendly and less self-conscious. Improved mood. With Noopept you may find yourself better able to deal with stressful situations and work issues that normally get you down. Once you get past the first few weeks of unpleasant memories related to PTSD you may find overwhelming emotions will subside. You could feel detached in a pleasant way from painful memories. Music appreciation. Many users report increased pleasure when listening to music while using Noopept. For some it takes music to a different plane. Distinguishing between instruments in sound tracks is easier. As a whole, music sounds better. Long-term memory. Noopept affects NGF and BDNF which affects long-term potentiation. Some neurohackers report memories long forgotten suddenly spring up. Which could be good or bad I suppose depending on the memory. But reports say memories are clear. And if they’re unpleasant there is an emotional detachment shielding from unpleasant feelings.

You should be able to experience the effects of Noopept soon after you take it. It’s water-soluble and enters your cells quickly especially if you take it sublingually. A word of caution, however, don’t go over the recommended 10 – 30 mg per day dose! You will not experience any added benefit and could bring on unwanted side effects. There is some debate on the water-solubility of Noopept. It’s not truly fat-soluble but it certainly doesn’t hurt to use a quality “good fat” when taking your Noopept dose. The Research Noopept increases Nerve Growth Factor & BDNF A study published by the Russian Academy of Medical Sciences in Moscow shows that Noopept stimulates Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). In this study, researchers studied the effect of single and long-term treatment (28 days) of Noopept. They found that one-time treatment boosted mRNA in the cerebral cortex of rats. mRNA is a molecule in brain cells that carries codes from DNA where they specify the amino acid sequence of proteins. And long-term treatment of Noopept increased Brain-Derived Neurotrophic Factor (BDNF). The researchers speculated that this sequence of events in the brain plays a role in the restoration of neurons. Improving neurotrophin synthesis in the hippocampus boosts cognitive function. Particularly

consolidation and delayed memory retrieval. The research team concluded that Noopept “holds much promise to prevent the development of Alzheimer’s disease in patients with mild cognitive impairment”.643 Noopept boosts Brain Waves Researchers in Moscow studied the effects of injecting Noopept in rats to see how it would affect brain waves. The team found that Noopept increased Alpha and Beta brain wave activity throughout the brain. You experience Alpha waves as you become more relaxed. Alpha waves are associated with superlearning, flow state and joy. Beta waves are associated with concentration, alertness and cognition. The researchers observed that NMDA receptors were involved with a single injection of Noopept. While AMPA receptors were activated after longer-term use of Noopept.644 NMDA receptors are associated with Long-Term Potentiation (long-term memory) and neuroplasticity. AMPA receptors are associated with increased brain signaling activity. Boosting cognition and memory. Noopept improves memory Noopept is known within the nootropic community for enhancing memory. And dozens of studies support this claim of better memory when using Noopept. One study done at the Russian Academy of Medical Sciences in Moscow experimented with Noopept on rats. The animals were trained in passive avoidance response. The animal’s ability to both form a memory and retain a memory was impaired. But once the rats received a dose of Noopept, they were able to retain a memory and retrieve that memory later. In other words, Noopept normalized learning capacity in animals with damage done to their cerebral cortex. And promoted training ability in rats with a hereditary learning deficit. The researchers noted that “Noopept improves all three stages of memory”. And was most pronounced in those with impaired memory function.645 Another study, again done with rats noted that Noopept stimulated learning after just a single administration. And repeated administration actually increased the number of successful learners among the animals who failed the initial training.646 Dosage Notes Recommended Noopept dosage is 10 - 30 mg per day. Noopept is very bioavailable and easily crosses the blood-brain barrier.647 Noopept is sold in tablet, capsule, and powder form. Tablets and capsules are usually 10 mg each. Noopept is primarily water-soluble nootropic but won’t easily dissolve in water or juice. So it may help

if you take it with a meal containing healthy fats. Or with a tablespoon of extra virgin, expeller coldpressed coconut or olive oil. Or other similar healthy fat to ensure quick absorption. For even quicker absorption you can use Noopept sublingually. Let the tablet or powder dissolve under your tongue so it can go straight into your blood-stream, and into your brain. Bypassing your digestive system completely. Side Effects Noopept is a synthetic nootropic and consider non-toxic. So is considered well-tolerated and safe. As long as you stay within the recommended dosage. Side effects are rare but can include fatigue, headaches, insomnia or stomach upset. Side effects are often a result of unusually high doses of the nootropic. Headaches from using Noopept typically happen when you forget to combine it with a good choline supplement. Headaches are often a symptom of a choline deficit in your brain. Available Forms Noopept is sold in tablet, capsule and powder form. Tablets and capsules are usually 10 mg each. In Russia and some other Eastern European countries, Noopept is a prescription drug. Nootropics Expert® Recommendation Noopept 10 – 30 mg per day I recommend using Noopept as a nootropic supplement. Your body does not make Noopept on its own. So to get its benefits you must take it as a supplement. Noopept is especially helpful for those looking to boost cognition, memory and recall. This nootropic helps boost the activity of acetylcholine in your brain. It modulates glutamate receptors which normalizes optimal neurotransmitter function. And increases Nerve Growth Factor (NGF) and BrainDerived Neurotrophic Factor (BDNF) which helps the neuroplasticity needed for Long-Term Potentiation. Noopept is also particularly useful to students and executives who want to boost cognition, learning and memory. My experience using Noopept shows it helps boost study scores, work flow, learning and memory. Noopept also helps improve verbal fluidity and sociability. Words seem to come easily, and vocabulary you didn’t know you had access to come into play. Music sounds richer and fuller, and your listening experience enters a new level of music appreciation. You should use Noopept with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain.

You should not exceed doses of more than 30 mg per day. Start with 10 mg and see how you respond.

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Oat Straw Oat Straw has been shown to relieve stress and anxiety, increase energy, boost cognition, and improve libido Oat Straw (avena sativa) is green oat grass. The tops of the oat plant in the milky stage before mature oat plants form a head. Avena sativa, or the common oat plant is a popular cereal grain that has been used by humans as nutrition for at least 3,000 years. Oats are grown in temperate climates world-wide as food for humans and livestock. And as an ingredient used in cosmetics. The oat plant is descended from avena sterilis, a wild oat that originated in the ‘Fertile Crescent’ that spanned from Israel to western Iran to Europe. It was domesticated about 3,000 years ago in Europe. Tea brewed from oats has traditionally been used as a sedative. And as an herbal treatment for insomnia and nervous disorders. In 1987, the German Commission E declared oat straw be used as a “nervine herb”. The Commission determined that oat straw extract was an effective herbal remedy for anxiety and stress (i.e. nerves).648 The nootropic benefits of Oat Straw were first revealed in the Middle Ages in Europe. In was recommended for boosting mental health, and as a restorative to the nervous system.649 Saint Hildegard of Bingen, a nun and herbalist born in 1098 in what is now present-day Germany, considered oats to be a favorite ‘happiness’ herb.650 Avenanthramides (bioactive compounds unique in oats) have been shown to enhance nitric oxide (NO) production in human smooth muscle cells.651 And have anti-inflammatory, anti-proliferative, and antiitching activity. Protecting against heart disease, colon cancer and skin irritation.652 Oat straw extract inhibits phosphodiesterase type 4 (PDE4). PDE4 is a component of signaling pathways involved in the mediation of antidepressant activity.653 Oat straw has a reputation in men’s health as a sexual performance enhancer. More recent studies have shown oat straw can improve cognitive performance as well. PDE4 inhibitors can prolong the effects of cAMP in the brain which can improve long-term memory, wakefulness, is neuroprotective, works as an anti-inflammatory and antidepressant. Oat straw extract inhibits monoamine oxidase B (MOA-B) which increases dopamine levels in the brain. Helping brain disorders like ADHD and Parkinson’s Disease.654 Oat straw extract suppresses inflammatory cytokines by inhibiting nuclear factor κB (NF-κB) activation655 Cytokines are implicated in a number of brain disorders including major depression,

schizophrenia and Alzheimer’s Disease.656 How does Oat Straw work in the Brain? Oat Straw boosts brain health and function in several ways. But two in particular stand out. 1. Oat Straw boosts cerebral circulation. Oat straw extract increases blood flow to and within the brain through several mechanisms of action. Oat straw contains the amino acid arginine which synthesizes to create nitric oxide (NO). NO dilates blood vessels allowing more blood to flow. Avenanthramides (bioactive compounds unique in oats) have been shown to enhance nitric oxide (NO) production in human smooth muscle cells. And the suppression of inflammatory cytokines in combination with increased nitric oxide increases blood flow. A study with 37 healthy older adults (60+ years) participated in a 24-week randomized, double-blind, placebo-controlled trial. Participants received 1500 mg per day of oat straw extract or a placebo. The study showed that cerebral vascular responsiveness increased by 42%. This indicates that the middle cerebral artery was able to dilate in response to stress.657 And more blood flow to the brain increases oxygen and nutrient delivery to brain cells. 2. Oat Straw increases Alpha Brain Waves. You experience alpha brain wave patterns as you become more relaxed. And is associated with super-learning, flow states and joy. German researchers conducted a double-blind, randomized, placebo-controlled crossover study using 1,250 or 2,500 mg of oat straw extract compared to placebo. An EEG was used to measure brain wave frequencies in this trial. The researchers noted that oat straw extract affected brain wave patterns in an area of the brain associated with cognition. The subjects performed better in arithmetic with fewer errors.658 How things go bad Ever noticed how older people seem more frail? They suffer from cognitive dysfunction and an overall decline in well-being. Research show these conditions are associated with a drop in dopamine levels as we age.659 ↓ Dopamine levels decrease ↑ Monoamine oxidase B (MOA-B) increases ↓ Mood, cognition and bodily function decline Dopamine levels begin to decline by 13% per decade after age 45.660 Cognition, mood and sexual function all suffer as a result. And gradually progress into diseases such as Alzheimer’s and Parkinson’s. Oat Straw benefits

Researchers have found that this age-related decrease in dopamine is caused by an enzyme called monoamine oxidase-B (MAO-B). In our youth, MAO-B regulates the exact amount of dopamine we need in our brain. But as we age, MAO-B levels get out of hand and increase too much.661 As MOA-B levels rise, dopamine levels fall. Research has shown that inhibition of MOA-B preserves brain function by protecting dopamine. And extends cognition, sexual function and life span.662 Oat Straw extract has been found to inhibit MOA-B and enhance dopamine that normally declines with age.663 Oat straw extract can: • • • • • •

Work as an antidepressant Help you cope with stress Reduce anxiety Control inflammation Relieve skin irritation Increase libido and sexual performance

How does Oat Straw feel? Most neurohackers report that supplementing with oat straw extract increases energy levels and libido. Others report more mental clarity, less anxiety, and an overall sense of well-being. Men say it increases libido and morning wood. The Research Oat Straw Improves Memory An Australian study was conducted with a group of elderly people. Some showed signs of mild cognitive impairment while others showed no impairment. Researchers wanted to measure cognitive performance after taking oat straw extract. Subjects were randomly assigned to receive a single dose of oat straw extract once a week. The study used 0 mg, 1,600 mg or 2,400 mg of oat straw extract. This was a “crossover” trial which means each subject was rotated through all 3 doses. So each participant functioned as a “control” during the trial. Researchers used the Stroop Color-Word Test which measures memory, executive function, catching errors, appropriate responses and attention. In this study, those who did not use oat straw extract had an average of 3.39 errors on the test. Those receiving 1,600 mg made only 1.2 errors (a 65% improvement). The subjects who reported no cognitive impairment did even better with an average of 0.55 errors

compared to placebo who averaged 2.13 errors (a 74% improvement). The 2,400 mg subjects performed about as well as those taking a placebo. The 2,400 mg dose of oat straw extract is significant because it shows that suppressing MAO-B too much will not improve cognition.664 Oat Straw for Improved Cognition A study using oat straw extract (Neuravena®) assessed the effects of a single dose with healthy adults aged 40 – 65 years with self-declared memory decline. Participants received a single dose of 800 or 1,600 mg of oat straw extract. Cognitive function was assessed measuring attention, spatial-working-episodic memory and executive function before dosing. Testing was done 1, 2.5, 4 and 6 hours after dosing. The results showed that 800 mg of oat straw extract increased speed of performance. Participants experienced improved performance of delayed word recall in terms of errors. And executive function in terms of decreased thinking time and overall completion time. The researchers concluded that acute (one-time) dosage of oat straw extract produced optimal effects on cognition at or below 800 mg. Once again showing that when inhibiting MOA-B, too much inhibiting does more harm than good.665 Oat straw extract enhances attention and concentration without the side effects of insomnia, nervousness, or anxiety. Dosage Notes Oat straw extract recommended dosage: • • •

Oat straw powder in a capsule is 350 mg up to 3-times daily Oat straw tincture ½ to 1 teaspoon up to 3-times daily Oat straw tea up to 3 cups per day

Most clinical studies showed the most effective dose to be between 800 – 1,600 mg per day. You should not exceed the recommended dosage because studies show that inhibiting MOA-B in excess will not provide the benefits normally associated with oat straw supplementation. Side Effects Oat straw is natural, non-toxic, and considered very safe. Exceeding recommended doses however can inhibit MOA-B too much and you will not get the cognitive benefit you’re looking for with oat straw. Available Forms Oat straw is available as powdered leaves and stems in capsule form, oat straw extract standardized 10:1 or 20:1, and alcohol extract tinctures.

Neuravena® (EFLA®955) is a patented oat straw extract made by Frutarom Health and licensed to some supplement manufacturers. Nootropics Expert® Recommendation Oat Straw extract 800 – 1,600 mg per day I recommend using Oat Straw as a nootropic supplement. Your body does not make Oat Straw on its own. So you must take it as a supplement. Oat Straw is especially helpful for those dealing with dopamine decline due to aging. As we age and particularly past age 40, MOA-B is produced in excess in our brains which causes dopamine to decline. Declining dopamine levels affect cognition, sexual function, mood and longevity. Oat straw extract is a natural inhibitor of MOA-B and will help restore dopamine to youthful levels. Oat Straw is also helpful for those suffering from Parkinson’s or Alzheimer’s disease. Increased MOAB, loss of dopamine receptors, and declining dopamine levels all contribute to neurodegenerative disease. Studies have found that using oat straw extract early in the diagnosis of disease can help alleviate symptoms of these diseases. You can safely take up to 1,600 mg of Oat Straw extract daily if needed. Half the dose first thing in the morning. And the other half early afternoon. Oat straw extract acts as a stimulant so avoid taking it too late in the day or it may affect sleep. Do not exceed recommended doses (more than 1,600 mg) of oat straw extract. You’ll suppress MOA-B too much which can mess with dopamine levels in your brain.

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Oxiracetam Oxiracetam has been shown to improve short and long-term memory, boost concentration and focus, improve cognition and increase cognitive energy Oxiracetam (4-Hydroxy-2-oxopyrrolidine-N-acetamide or ISF-2522) is a water-soluble Ampakine nootropic in the racetam-class of compounds. Oxiracetam is considerably more potent than the original racetam, Piracetam.666 Oxiracetam was the 3rd racetam nootropic developed in the 1970’s. It is chemically derived from Piracetam (2-oxo-1-pyrrolidinoacetamide) where the main difference is the addition of a hydroxyl group. Oxiracetam, similar to other racetam nootropics, has a pyrrolidone nucleus at its core. Oxiracetam modulates AMPA-sensitive glutamate receptors and increases neurotransmitter release.667 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic) refers to one of three glutamate receptors in your brain.668 A favorite racetam among the nootropics community. Neurohackers use Oxiracetam to boost memory and learning, support brain health and for its mild stimulant properties. Oxiracetam helps: • •

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Brain Optimization: Oxiracetam significantly improves cognition and memory, sensory perception and reflexes. Focus and concentration get a boost. And recall is easier. Neurotransmitters: Oxiracetam enhances choline-acetyltransferase (ChAT) in your brain.669 ChAT is the enzyme responsible for acetylcholine (ACh) synthesis. ACh is the neurotransmitter critical for encoding new memories, reasoning, concentration, cognition and neuroplasticity. Brain Energy: Oxiracetam modulates AMPA-receptors in your brain. Ampakines provide a stimulant-effect by influencing glutamate receptors. Without any of the side effects associated with stimulants.670 Oxiracetam also seems to boost ATP synthesis in brain cells.671

Oxiracetam is sold as an over-the-counter, unrestricted compound in much of the world including the United States. Oxiracetam is considered to be more potent than Piracetam. As an ampakine nootropic, it helps increase attention span, alertness and boosts memory. Including the ability to form long-term memories even if taken after the initial memory formation.672 Ampakines tend to have a stimulant effect. But do not produce the same stimulant side effects as Ritalin or coffee from prolonged use. Oxiracetam vs. Piracetam: What’s the Difference? Oxiracetam was developed in the 1977 as a derivative of Piracetam. Oxiracetam and Piracetam are both water-soluble. The half-life and nootropic benefits are similar.

The potency of Oxiracetam seems to be about 5-times that of Piracetam. So it’ll take less to get the same nootropic effect. Both Oxiracetam and Piracetam are cognitive enhancers. And both have neuroprotective qualities. Both racetams are able to improve learning and memory. And both are able to repair brain damage. Oxiracetam has additional benefits not shared with Piracetam. Oxiracetam provides more of a stimulatory effect than Piracetam. Some even compare it to Modafinil. Many prefer Oxiracetam over Piracetam. But if you’re a first-time user of Oxiracetam, start with a lower dose and see how you react to it. And make sure you stack it with a good choline source to avoid the racetam-headache and irritability sometimes associated with racetams. How does Oxiracetam Work in the Brain? Oxiracetam boosts brain health and function in several ways. But two in particular stand out. 1. Oxiracetam boosts memory and cognition. Oxiracetam modulates AMPA receptors in the brain. These receptors work like control channels, overseeing and regulating synaptic transmission. Oxiracetam also increases the density of binding sites for neurotransmitters on AMPA receptors.673 The result of these actions is a stimulant-effect without any of the negative side effects associated with stimulants. And there is clinical evidence that this stimulant action has an effect on memory and cognition. One double-blind, placebo controlled trial was done with 65 patients diagnosed with primary degenerative dementia. Patients were given 800 mg of Oxiracetam twice daily for 12 weeks, or a placebo. Subjects were tested before the trial, and after 6 and 12 weeks of treatment. The researchers found a significant difference in favor of Oxiracetam based on a ‘quality of life scale’, and several neurological tests for memory.674 Oxiracetam also seems to prevent an imbalance of acetylcholine activity when NMDA receptors are malfunctioning.675 AMPA and NMDA receptors work together for the flow of glutamate necessary for learning and memory processes. Including Long-Term Potentiation that is associated with neuroplasticity that allows long-term memories to form. 2. Oxiracetam boosts the availability of acetylcholine (ACh) in the brain. Leading to improved short-term and long-term memory. And eliminating ‘brain fog’. Oxiracetam does this by boosting the sensitivity of ACh receptors. Oxiracetam enhances protein kinase C (PKC) which affects M1 acetylcholine receptors. Oxiracetam even demonstrates the ability to repair these receptors when damaged.676 More ACh results in better memory and learning. How things go bad

Glutamate is an excitatory relative of GABA. While GABA has a calming effect, glutamate stimulates. Glutamate is the most common neurotransmitter in the central nervous system. Glutamate is a pivotal neurotransmitter in the brain. It links the brain circuits involved in memory, learning and perception. ↓ Too little glutamate can cause problems with memory, learning and perception ↓ AMPA and NMDA receptors wear out or die ↓ Acetylcholine levels decline ↓ Cholinergic neurons wear or die out All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Oxiracetam can help for age-related cognitive decline, as well as a student looking to do better in school. By boosting acetylcholine and controlling glutamate in the brain. Oxiracetam benefits Clinical studies have looked at using Oxiracetam to treat Alzheimer’s, ADHD, dementia, concussions and other brain disorders. Many of these trials demonstrated Oxiracetam’s ability to improve learning, spatial learning performance, memory, recall and quality of life scores. Oxiracetam works similar to other racetams by targeting the neurotransmitters acetylcholine (ACh) and glutamate. Acetylcholine has a significant impact on memory formation and recall. And glutamate plays a role in memory formation, motivation and attention. Oxiracetam encourages the use of acetylcholine in your brain. So when using Oxiracetam you must ensure you have adequate choline levels available to make acetylcholine. Most neurohackers stack Oxiracetam with a choline supplement like Alpha GPC or CDP-Choline. Oxiracetam is used to boost short and long-term memory, eliminate brain fog, improve attention and focus, and the ability to learn. How does Oxiracetam feel? Nootropics users report that Oxiracetam clears brain fog, improves focus and motivation. Especially when learning new material or working through a tedious task. You could see a significant improvement in recall. Reading is easier giving you the ability to get through more pages faster and retain the information for later. And some report an improvement in mood which could be the result of more acetylcholine available for use in the brain. Oxiracetam does have a stimulant-effect so try not to take it too late in the day as it may interfere with a

good night’s sleep. You should be able to experience the effects of Oxiracetam soon after you take it. It’s water-soluble so it’s digested and enters your cells quickly. And unlike other stimulants, there is no “crash” once Oxiracetam leaves your system. The Research Researchers worked with 96 patients diagnosed with dementia for 12 months. Patients were treated with 1600 mg per day of Oxiracetam or a placebo. And were assessed at 2, 6 and 12 months of the trial. The patients treated with Oxiracetam showed a significant improvement in reaction time and cognition. The placebo group experienced a worsening of conditions. The study authors concluded that Oxiracetam favorably acts on the symptoms of dementia. And can improve information processing, reaction times and attention.677 Oxiracetam helps Traumatic Brain Injury Traumatic brain injury (TBI) is a major public health issue affecting 1.7 million Americans each year.678 TBI can be caused by sports injuries, work accidents, car and motorcycle accidents, falls, and your wife hitting you over the head with a frying pan. Many survivors end up with long-term or even permanent neurocognitive dysfunction. Affecting cognition, motor function (movement) and personality. These disabilities are estimated to cost $9.2 billion in lifetime medical costs and $51.2 billion in productivity losses.679 In a brain subjected to TBI there is glutamate toxicity, free-radical injury to brain cells, electrolyte imbalances, mitochondrial dysfunction, inflammation, apoptosis (cell death) and stroke.680 In one study done with 30 Wistar rats, researchers looked at the role Oxiracetam could have on TBI. The animals were randomly divided into 3 groups. Rats in the treatment group were given 100 mg/kg of Oxiracetam for 21 days. Neurologic impairment scores were measured on days 1, 4, 7, 14 and 21. The researchers found the treatment group has significantly less brain impairment after 7, 14 and 21 days. And concluded that Oxiracetam shows promise in decreasing neural injury caused by TBI. Increasing learning ability, memory and space cognition.681 Oxiracetam Improves Cognition and Memory Researchers worked with 43 patients to evaluate the effects of Oxiracetam on ‘organic brain syndrome’ (OBS). OBS is brain dysfunction that is not attributable to a specific disease like Alzheimer’s or dementia. This double-blind, placebo-controlled study had one group of patients taking 800 mg of Oxiracetam twice a day for 8 weeks, and the other group took a placebo. In OBS patients with mild to moderate cognitive impairment, Oxiracetam improved cognition, logic and attention. The placebo group experienced no change in cognitive impairment.682

Another study with memory impaired rats showed that Oxiracetam restored acetylcholine receptors. Restoring learning and memory as a result.683 Dosage Notes Recommended Oxiracetam dosage is 750 – 1,500 mg per day. Divided in two equal doses. One Oxiracetam dose in the morning, and one in the early afternoon. Oxiracetam is sold in tablet, capsule, and powder form. Tablets and capsules are usually 750 mg each. Since Oxiracetam boosts the efficiency of acetylcholine in your brain, you should stack it with a good choline source like Alpha GPC or CDP Choline. Side Effects Oxiracetam non-toxic. So is considered well-tolerated and safe. Side effects are rare but can include anxiety, fatigue, headaches, nervousness and nausea. Side effects are often a result of unusually high doses of the nootropic. Headaches from using Oxiracetam typically happen when you forget to combine it with a good choline supplement. Headaches are often a symptom of a choline deficit in your brain. Available Forms Oxiracetam is sold in tablet, capsule, and powder form. Tablets and capsules are usually 750 mg each. Nootropics Expert® Recommendation Oxiracetam 750 – 1,500 mg per day I recommend using Oxiracetam as a nootropic supplement. Your body does not make Oxiracetam on its own. So to get its benefits you must take it as a supplement. Oxiracetam is especially helpful for those suffering from lack of energy, brain fog and the inability to focus. Oxiracetam influences AMPA and NMDA receptors in your brain. Improving the efficiency of the neurotransmitter glutamate. This excitatory brain chemical is responsible for sending signals between neuron in the brain. And plays a critical role in learning and forming memories. Oxiracetam is also particularly useful to students and executives who want to boost cognition, learning and memory. It boosts the efficiency of the neurotransmitter acetylcholine (ACh) in your brain. ACh is critical for encoding new memories, reasoning, concentration, cognition and growth of new synapses (neuroplasticity). Oxiracetam also helps improve verbal fluidity and sociability. Words seem to come easily, and vocabulary you didn’t know you had access to come into play. You should use Oxiracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps

boost neural acetylcholine, so demands the presence of more choline in your brain. You can safely boost daily intake of Oxiracetam to 2,800 mg if needed.

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Passionflower Passionflower is known for improving sleep quality, reducing anxiety, and promoting healthy brain GABA levels. Passionflower (Passiflora incarnata, Passiflora caerulea, Passiflora edulis, Passiflora foetida) is a perennial vining plant native to Central and South America. It produces white with lavender-fringed flowers having 10 white petals, and a central crown of pinkishpurple filaments. There are over 520 different species belonging to the Passifloraceae family. In the southeastern United States, it is often called Maypop, named after the edible fruit, it produces a “pop” when crushed. Passionflower was known to Native Americans as an herbal remedy long before the Spanish conquistadors arrived. The name Passionflower came from Roman Catholic priests in the 1500’s. They reported seeing symbols of the Passion of Jesus Christ in the parts of the plant. Used for centuries by Native Americans, Passionflower is known for its ability to reduce anxiety and insomnia. Recent clinical studies confirm the neuroscience showing Passionflower as being effective for these traditional uses. Passionflower has sedative properties that help calm you.684 It has been shown to reduce anxiety. Including before surgery. The flavonoids found in Passionflower are partial agonists of GABAA receptors and inhibit the uptake of GABA into synapses.685 Passionflower modulates the levels of GABA in your brain. Passionflower inhibits GABA uptake in synapses without affecting GABA release or GABA transaminase activity.686 Passionflower supports healthy sleep.687 It has been shown to improve sleep quality and feeling refreshed the next morning.688 The flavonoids in Passionflower include apigenin, luteolin, quercetin, and kaempferol.689 Passionflower is used for anxiety, Generalized Anxiety Disorder (GAD), symptoms of opiate withdrawal, insomnia, nerve pain, convulsions, bronchial spasms, ADHD, palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction, and menopause.690 New studies are emerging that look at the science behind these uses and other possible benefits of Passionflower. Including helping with panic attacks, seizures, headaches, menstrual pain, and Parkinson’s disease. How does Passionflower work in the brain? Passionflower boosts brain health and function in several ways. But two in particular stand out.

1. Passionflower is anti-anxiety. The symptoms of anxiety and depression are often due to an imbalance of excitatory and inhibitory neurotransmitters in the brain. One mechanism involves the GABA system and a GABAA (benzodiazepine) receptor which is the binding site of benzodiazepines, and which regulate chloride flow through ion channels.691 Studies show the anxiolytic activity of Passionflower is due to Passiflora apigenin and chrysin which are partial agonists of the same GABAA receptors.692 One randomized, double-blind clinical trial was conducted with 40 volunteers who were about to undergo an anxiety-inducing tooth extraction. The volunteers were given 260 mg of Passionflower or 15 mg of midazolam 30 minutes before surgery. The researchers concluded that Passionflower showed anxiolytic effects similar to midazolam. And was a safe and effective sedation alternative for adult patients undergoing a tooth extraction.693 2. Passionflower for sleep. Passionflower is a traditional herbal sedative, anxiolytic, and popular sleep aid used for the treatment of insomnia. And several clinical studies have demonstrated its efficacy as a sleep aid in lab animals. But clinical trials in humans were lacking So, researchers at Monash University in Australia decided to investigate Passionflower herbal tea on human sleep. 41 volunteers aged 18 - 35 were selected to participate in the experiment. Each study participant consumed a cup of Passionflower tea and filled out a sleep diary daily for 7 days. Of the 6 sleep-diary measures analyzed, sleep quality showed a significantly better rating for Passionflower compared to the placebo. The researchers concluded that the consumption of low-dose Passionflower tea resulted in sleep benefits for healthy adults with mild fluctuations in sleep quality.694 How things go bad Passionflower modulates how GABA works in your brain. It works as a GABAa receptor antagonist.695 Dysfunction of the GABA system is implicated in several neuropsychiatric conditions. Which can result in: ↑ Increased anxiety ↑ Increased symptoms of depression ↑ Poor sleep quality including insomnia696 ↓ Memory, cognition, and decision-making ability suffers ↓ Declines in quality of life

Supplementing with Passionflower may help relieve anxiety and depression, improve your quality of sleep, and your overall sense of well-being. Passionflower benefits Hundreds of peer-reviewed clinical studies have been published on the benefits of Passionflower. Passionflower has been well-established as an anxiolytic and sedative.697 Passionflower has also been shown to: • • • • • • • • •

Reduce general anxiety698, 699 Reduce anxiety before surgery700, 701 Treat insomnia702 Improve sleep quality703, 704 Modulate GABA levels in your brain705, 706 Work as an anti-inflammatory and antioxidant707 Have potential for Parkinson’s disease708 Help in the treatment of opiate withdrawal709 Reduce hot flashes and night sweats associated with menopause710

How does Passionflower feel? Neurohackers report improved sleep quality with Passionflower. They say it helps them fall asleep and sleep more deeply. Some report Passionflower helped them taper off opiates with fewer withdrawal symptoms including better sleep and less anxiety. One person who calls herself a “Type A” personality said it “helps shut my brain off and drift into sleep peacefully.” Unlike using sleep meds, neurohackers say when using Passionflower for sleep they don’t feel as “zonked out” as they do when using sleep meds. Sleep is better and it’s easier to get going the next morning. Many Passionflower users say it provides relief from anxiety. It “takes the edge off” and helps them work past their anxiety instead of becoming paralyzed by it. Passionflower helps calm you but without the side effects associated with anti-anxiety meds. And you cannot become physically dependent on it like you can with anti-anxiety drugs. Passionflower Clinical Research Passionflower has been used for millennia to reduce anxiety and for restful sleep. It’s also used for panic attacks, seizures, hypertension, headaches, and menstrual pain.711 Passionflower is often combined with other nootropic herbs such as Valerian or Lemon Balm for insomnia. And with St. John’s Wort for depression.

Passionflower compared to an Anti-Anxiety Med A randomized, double-blind, controlled study published in the Journal of Clinical Pharmacy and Therapeutics examined the effect of Passionflower on Generalized Anxiety Disorder (GAD). It compared the efficacy of Passionflower to oxazepam, a pharmaceutical sedative. 36 Patients diagnosed with GAD were randomly assigned to receive either 45 drops/day of Passionflower extract, or 30 mg/day oxazepam for 4 weeks. The study found that Passionflower extract was equally effective as oxazepam for treating GAD. The researchers concluded, “The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage.”712 Passionflower for anxiety before surgery Patients who undergo anesthesia before surgery typically experience anxiety. A research team at Ankara Training and Research Hospital in Turkey conducted a study using Passionflower with 60 patients aged 25-55 years about to get spinal anesthesia. Their intention was to investigate the efficacy of Passionflower on anxiety, psychomotor function, sedation, and blood pressure when taken as a supplement prior to anesthesia. The patients received Passionflower syrup (700 mg/5 mL aqueous extract) or a placebo 30 minutes before spinal anesthesia. After the surgery was complete the researchers concluded “oral administration of Passionflower suppressed anxiety before spinal anesthesia without changing psychomotor performance or blood pressure and produced no side effects”.713 Passionflower for sleep A double-blind randomized placebo-controlled clinical study published in 2020 examined the effect of Passionflower on insomnia. A research team at the Soonchunhyang University College of Medicine in Korea used polysomnographic technology to investigate the effects of Passionflower in subjects suffering from insomnia. Polysomnography, also called a sleep study, is a comprehensive test used to diagnose sleep disorders. Polysomnography records your brain waves, the oxygen level in your blood, heart rate and breathing, as well as eye and leg movements during a study. 110 adult participants with an average age of 40 years old and who were diagnosed with insomnia disorder were included in the study. The patients received either Passionflower extract or a placebo for 2 weeks. Patients underwent an overnight polysomnography and completed sleep diaries as well as several other tests used to measure sleep quality and duration.

Sleep efficiency and wake after sleep onset (WASO) significantly improved after 2 weeks in the Passionflower group but no change in sleep with the placebo group. The researchers concluded that Passionflower demonstrated a positive effect on sleep and relieving insomnia.714 Passionflower Recommended Dosage The recommended nootropic dosage for Passionflower extract for anxiety is 250-1,000 mg per day. Larger doses should be divided into 2 or 3 smaller doses during your day. Recommended dosage of Passionflower extract for sleep is 200 – 400 mg before bed. Recommended dosage of Passionflower tincture is 0.5-2 ml 3- times per day. Recommended dosage of Passionflower tea is 0.25-2 grams of dried Passionflower per cup of tea, steeped for 10-15 minutes. Taken 2 or 3-times per day. Doses of Passionflower extract above 3.5 grams per day may be toxic and unsafe. Remember, more is never better when using nootropics.715 Passionflower Side Effects Passionflower is considered non-toxic and safe when used at the recommended dosage. Side effects are rare but can include drowsiness, confusion, reduced coordination, nausea, headache, or rapid heartrate. Passionflower has the potential to interact with several drugs and you should not take it if you take sleep aids, tranquilizers, sedatives, MAOIs, anticoagulants or blood pressure medication. Passionflower may slow blood-clotting.716 Passionflower may lower blood pressure. Passionflower should not be used if you are pregnant because human studies show using herb while pregnant can result neonatal death, premature rupture of membranes, newborns taking amniotic fluid into their lungs, or newborn high blood pressure.717 Type of Passionflower to Buy Passionflower supplements are made from the flowers, leaves, and stems of the plant. It’s available in capsule, tincture, and dried herb form. Pascoflair® is made by Pascoe which is headquartered in Giessen, Germany. Pascoflair® is a patented Passionflower extract with 425 mg dry extract in tablet form. Passionflower extract in capsules range from 200 mg to 1100 mg each. Passionflower tinctures are available as alcohol or water extracts and sold in small dropper bottles. Follow dosage recommendations provided by the manufacturer in the bottle label. Look for Passionflower supplements that are preferably certified organic, non-GMO, produced in a

GMP facility, and contains zero fillers or other toxic “other ingredients”. Nootropics Expert® Recommendation Passionflower extract 250-1,000 mg per day I recommend using Passionflower as a nootropic supplement. Your body does not make Passionflower on its own. So, you must take it as a supplement. Passionflower is especially helpful for those suffering from anxiety, chronic stress, and insomnia. Passionflower helps reduce anxiety by naturally modulating GABA levels in your brain and working as a GABA receptor antagonist. Supplementing with Passionflower before surgery can help reduce the anxiety you normally experience in anticipation of the surgical procedure. Passionflower is also helpful if you have problems with sleep. It improves sleep quality if you are dealing with insomnia without affecting your performance the following day. Women going through menopause find supplementing with Passionflower helps reduce hot flashes and night sweats. Passionflower may help you taper off opiates with fewer withdrawal symptoms including better quality sleep and less anxiety. You can safely take up to 1,000 mg of Passionflower extract if needed. If you are using it for anxiety, try 500 mg in the morning and another 500 mg in the afternoon. Passionflower as a sleep aid seems to be particularly effective when stacked with Valerian or Lemon Balm. And combined with St. John’s wort for severe depression.

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Phenibut Phenibut has a calming effect on brain and body, helps relieve stress and anxiety, and boosts Human Growth Hormone Phenibut (β-Phenyl-GABA, β-phenyl-γ-aminobutyric acid, Noofen, Citrocard) is an analogue of the inhibitory neurotransmitter GABA. The addition of a phenyl ring allows Phenibut to cross the bloodbrain barrier (BBB). Neurohackers prefer Phenibut when the goal is to raise GABA levels in the brain because GABA as a supplement cannot cross the BBB. Clinical studies show that boosting GABA with a supplement like Phenibut relieves anxiety, stress, and boosts the production of alpha brain waves.718 If GABA is optimized in your brain you’ll feel focused, relaxed and stress-free. Phenibut helps: •

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Balance mood. Phenibut has an inhibitory effect on overly stimulated neurons because it raises GABA levels in your brain. Low GABA levels lead to anxiety, depression and insomnia. GABA helps restore that balance. Promoting a more positive mood which improves focus and relaxation.719 Boost Human Growth Hormone. Bodybuilders and athletes use Phenibut before resistance training. Studies show by raising GABA levels, you can boost blood levels of Human Growth Hormone.720 Promoting greater recovery support and lean muscle growth. Neurotransmitters. Phenibut stimulates dopamine receptors and antagonizes betaphenethylamine (PEA).721 Dopamine aids in memory formation, attention, focus, and cognition. PEA increases the action of dopamine, norepinephrine, acetylcholine and serotonin. It’s partly behind the overstimulation that causes irritability, restlessness, and agitation that could be caused by too much dopamine and norepinephrine. Phenibut can counteract this affect giving you a cognition boost without the negatives.722

GABA (gamma-aminobutyric acid) is the major inhibitory or relaxing neurotransmitter in your brain.723 GABA’s primary role is to keep the major excitatory neurotransmitter glutamate in check. GABA is naturally synthesized in your brain from glutamate. It’s estimated that 40% of the synapses in the human brain work with GABA and therefore have GABA receptors. So when using Phenibut to boost GABA, you enhance normal sleep cycles, and improve blood pressure. GABA even stimulates the pituitary gland to secrete Human Growth Hormone. And helps produce endorphins that make you feel good after a workout or sex. Soon after Phenibut was discovered in St. Petersburg, Russia, it was being prescribed by doctors to lower stress and anxiety, treat PTSD and insomnia. Phenibut was included in the medical kit for Russian astronauts on the Soyuz-19 and Salyut-4 missions as a ‘tranquilizer’.724 Phenibut is one of the only tranquilizers that lowers stress levels without

negatively affecting performance. As a nootropic, when you use Phenibut to normalize GABA levels you’ll experience a reduction in anxiety, insomnia, nervousness, restlessness and stress. Phenibut can be a more natural, safer alternative to Benzodiazepine drugs like Valium and Xanax. These pharmaceuticals work by increasing GABA receptor sensitivity.725 How does Phenibut Work in the Brain? Phenibut helps brain health and function in several ways. But two in particular stand out. 1. Phenibut boosts GABA in the brain. Phenibut is a derivative of GABA. And easily crosses the blood-brain barrier. GABA on its own cannot cross this barrier unless paired with a dedicated carrier.726 GABA works by preventing neural signaling associated with anxiety from reaching other neurons. It does this by attaching to the receptors that would otherwise excite those neurons. Over-stimulating neurons in certain areas of your brain is what causes anxiety-related symptoms. The majority of studies on Phenibut have been conducted in Russia. And most studies have been done with animals. In this study using rabbits, scientists looked at anxiety behaviors and how they were effected by Phenibut. They exposed the rabbits to emotional stimuli causing anxiety in the animals. Anxiety caused the rabbits to ‘freeze’ and exhibit defensive reactions. Behaviors very similar to what happens in humans when they’re under stress. When the rabbits were administered Phenibut, the anxiety-caused reactions of defensiveness and passive reactions (freezing) decreased to normal behavior.727 2. GABA changes brain waves. Using Phenibut as a nootropic helps increase GABA levels in your brain. And we know that GABA helps decrease Beta brain waves and increase Alpha brain waves.728 Beta brain waves are important for attention, alertness, concentration and developing memories. But excess levels of concentration, particularly during stress, can lead to anxiety, depression, insomnia and more stress. When you are in an alert state, both Alpha and Beta brain waves can be stimulated. But the type of alertness will determine which brain wave is produced. Alertness during an Alpha wave state is associated with a relaxed state. And a stressed alert state produces a Beta wave. But an excess of Beta brain waves contributes to a variety of nervous disorders including anxiety and stress. Most of the clinical studies available done with humans use GABA supplementation rather than Phenibut. But the outcome of using GABA could be applied to using Phenibut to increase GABA levels

in the brain. Phenibut crosses the blood-brain barrier more effectively than GABA. In this study, researchers investigated using GABA on relaxation and immunity during stress in humans. They evaluated the effect on 13 subjects of GABA intake on brain waves. An electroencephalogram (EEG) was used to measure brain waves after subjects took water only, GABA or L-Theanine. 60 minutes after administration, the study showed that GABA significantly increased Alpha waves and decreased Beta waves compared to water or L-Theanine. The researchers concluded that raising brain levels of GABA induced relaxation and diminished anxiety.729 And you raise brain levels of GABA effectively when supplementing with Phenibut. How things go bad Low levels of GABA are associated with a variety of health problems. ↑ Anxiety730, panic attacks, stress and insomnia ↑ Muscle spasms, hypertension, convulsion, Tourette’s Syndrome and epilepsy ↑ Dry skin and wrinkles ↑ Poor digestion, bloating, flatulence, and constipation When your neurotransmitters, including GABA, are in balance, you feel motivated, productive and energetic. And you feel calm and relaxed during downtime. When GABA levels are low you feel filled with dread, you’re constantly worried, you have racing thoughts, and you’re frequently late and disorganized.731 Many people in this GABA-slump resort to high carbohydrate foods, and drugs or alcohol to relax. Phenibut benefits Phenibut is an analogue of GABA. The addition of a phenyl ring allows Phenibut to cross the bloodbrain barrier much more easily than GABA taken as a supplement. We need adequate GABA levels in our brain because it’s an inhibitory neurotransmitter. When we raise GABA levels by supplementing with Phenibut, we help keep glutamate in check. Glutamate is your body’s most abundant excitatory neurotransmitter. Which is responsible for attention span, brain energy, learning ability, memory, and staying awake. So GABA is calming and glutamate is stimulating. And they must be in balance with each other for optimal cognitive health. An imbalance of these two neurotransmitters can cause fibromyalgia, chronic fatigue syndrome, poor memory and cognition, anxiety and depression. But when these two neurotransmitters work together efficiently, you feel relaxed with no stress or

feelings of anxiety. And you get a more restful night’s sleep. Adding Phenibut to your nootropic stack can help bring GABA and glutamate back into balance. How does Phenibut feel? When you balance GABA levels in your brain, you feel relaxed and calm. But many neurohackers who try using GABA as a supplement don’t feel the effects. Because the GABA molecule is too large to cross the blood-brain barrier.732 Note: If you do feel the calming effects of supplementing with GABA within a ½ hour of taking it, it may mean you have a “leaky” blood-brain barrier. Not a good thing.733 Because if GABA can get through, all kinds of nasty stuff can get through too. Including toxins, undigested food particles and anything else in your blood stream that shouldn’t be in your brain. But here were talking about increasing our GABA levels using Phenibut. Neurohackers report that adding Phenibut to their stack relieves anxiety, there is less stress and they feel more relaxed. In fact, some say it’s the best anti-anxiety ‘medication’ they’ve ever used. Including some well know pharmaceuticals (i.e. Clonazepam, Diazepam, Alprazolam) used to treat anxiety. With none of the nasty side effects that come with prescription meds. Social functions could get some help with Phenibut. You could feel less inhibited, speak freely, and feel more confident. Others report that Phenibut boosts sex drive, and for men it helps control ejaculation. And it helps for a better night’s sleep. Athletes report that Phenibut goes well with a workout. Because Phenibut has been shown to boost Human Growth Hormone. You’ll be able to work out with less fatigue, energy levels will go up, muscles won’t be as sore and recovery could be faster. Phenibut takes 2 – 4 hours before you begin to feel its effects. A strong word of caution: do not increase the dose or take additional Phenibut if you think things are not happening fast enough! Wait at least 24 hours before taking another dose. The Research GABA was identified as a neurotransmitter several decades ago. And there had been a lot of research on GABA published since. But most of it is focused on how GABA works. And the drugs and chemicals which affect its action. There is very little research available on using GABA as a supplement. Likely because most scientists believe that GABA taken as a supplement will not cross the blood-brain barrier. And there is even less research available on using Phenibut. Particularly in humans. Most of the clinical trials have been done in Russia and were done with animals.

Here we talk about how GABA can affect your cognition and overall health. This research supports the idea that using Phenibut to raise GABA levels can have a profound effect on your quality of life. GABA Increases Human Growth Hormone Bodybuilders and athletes use Phenibut or even GABA to help repair and build muscle. And there are several studies supporting the notion that GABA increases Human Growth Hormone. In one study, researchers worked with 19 subjects who were given a single oral dose of 5 grams of GABA. 18 subjects were given a placebo during this trial. 3 hours after the administration of GABA, blood samples were taken. The team reported that “GABA caused a significant elevation of plasma growth hormone levels”.734 GABA helps Reduce Insomnia A Los Angeles study conducted a randomized, double-blind, placebo controlled trial with 18 patients with sleep disorders. The patients received either a placebo, or Gabadone (a combination of GABA and 5-hydroxytryptophan). The difference between the two groups of sleep-deprived patients was significant. The Gabadone group fell asleep faster, stayed asleep longer, and had a better quality of sleep than the placebo group.735 Neurohackers consistently report a similar effect on sleep quality when using Phenibut. Dosage Notes The recommended daily starting dosage of Phenibut is 200 - 300 mg for a relaxation or calming effect. Give it 2 – 4 hours before it starts to kick in. More experienced Phenibut users go with 1 – 1 ½ grams per dose. And up to 3-times per week. Since you can quickly build up a tolerance to Phenibut dosing less often is preferred. Many advise keeping Phenibut use to once or twice per week with almost no side effects and no hangover the next day. Phenibut can be very addictive for some people and the withdrawal from continuous use is particularly nasty. So if you’re going to try Phenibut make sure you follow dosage recommendations. Side Effects Phenibut is considered safe when taken in normal recommended doses. Bodybuilders who use much higher doses of Phenibut do report experiencing flushing, tingling, a spike in heart rate and blood pressure, and anxiety. You can build up tolerance to Phenibut quickly. And if you have an addictive personality you should avoid using Phenibut. Most neurohackers suggest cycling Phenibut. Using recommended doses for 4 or 5 days and taking a few days off. Others suggest only using Phenibut once per week.

You’ll have to find out what works for you if you decide to try Phenibut. And expect to have a rough ride at first. Too much and the withdrawal can be nasty. You are strongly advised not to combine Phenibut with alcohol. And absolutely DO NOT combine Phenibut with benzodiazepines. Available Forms Phenibut as a supplement is available in tablet, capsule, and powder. Scientists have shown that Phenibut easily crosses the blood-brain barrier. Phenibut is an analogue of GABA developed in Russia, and it increases levels of GABA in your brain. While some report that Phenibut causes drowsiness and fatigue, it’s a much safer way to boost GABA than with a pharmaceutical like Valium or Xanax. Nootropics Expert® Recommendation Phenibut 200 – 300 mg per day. I recommend using Phenibut (with caution) as a nootropic supplement if you’re feeling anxiety or stress. And to calm or keep in check the stimulatory effects of some nootropics. Your body does make GABA on its own from glutamate in your brain. Most healthy people have an adequate supply of GABA. But if you’re dealing with anxiety or stress and need some extra help in calming things down, Phenibut can help. Phenibut is particularly helpful if you’re dealing with Post Traumatic Stress Disorder (PTSD). I’ve seen reports by combat veterans who say that Phenibut worked far better than any prescription anti-anxiety med. I suggest trying a Phenibut supplement first at a dose of 200 - 300 mg. Phenibut can be a powerful method of boosting GABA levels in your brain. But it also has addictive potential especially if you’re prone to addiction. Phenibut takes 2 – 4 hours to take effect in your body. Do not yield to temptation and take more just because you’re not feeling anything. Sometimes the beneficial effects of Phenibut are not felt until the next day. Cycle your use of Phenibut to avoid tolerance and side effects. Your sweet spot could be every 2nd or 3rd day. Or even just once a week. Find out what works best for you. The ‘hangover’ from abusing Phenibut is particularly nasty. You should be able to avoid these side effects by keeping doses low. And limiting the days you use Phenibut. You can safely work your way up to 1,500 mg of Phenibut per day on the day that you dose. Some athletes go as high as 3,000 mg. But for nootropic use, a higher dose is not necessary or recommended.

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Phenylalanine Phenylalanine enhances working memory, executive function, creative flow states, stress reduction, better mood, anti-anxiety and lessens symptoms of ADHD Phenylalanine is a highly bio-available essential amino acid. Your body naturally converts LPhenylalanine into the amino acid L-Tyrosine which is then converted into L-DOPA. Decarboxylation of L-DOPA results in synthesis of the neurotransmitter dopamine.736 Once converted into dopamine, the enzyme dopamine-beta-hydroxylase converts dopamine into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). This triad of neurotransmitters are collectively referred to as “catecholamines”. Phenylalanine is naturally found in protein-rich foods like soybeans, cheese, nuts, seeds, beef, lamb, chicken, pork, fish, eggs, dairy, beans, and whole grains. The artificial sweetener aspartame also contains Phenylalanine. As a nootropic supplement, you may find several different forms of Phenylalanine available. LPhenylalanine is the natural form found in proteins. D-Phenylalanine is a mirror image of LPhenylalanine that is made in the lab. And DL-Phenylalanine is a combination of the two forms.737 L-Phenylalanine can be a highly effective nootropic for boosting cognitive function because it boosts norepinephrine and dopamine production. Resulting in increased attention, motivation and working memory. D-Phenylalanine (but not L-Phenylalanine) has been used to treat chronic pain although the clinical research in this area is sparse. L-Phenylalanine also stimulates the production of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) which are crucial in maintaining both overall physical and cognitive health. L-Phenylalanine is an essential amino acid that you get from food or a supplement. The enzyme phenylalanine hydroxylase converts Phenylalanine in your liver into the amino acid L-Tyrosine.738 Many neurohackers prefer L-Phenylalanine over other catecholamine precursors because it supports neurotransmitter production without directly increasing neurotransmitter levels. This last part is key because indiscriminately increasing neurotransmitters across the board can lead to imbalances and tolerance. Which can defeat the purpose of taking the nootropic in the first place. For example, not enough epinephrine can decrease cognition. And too much norepinephrine can decrease attention, processing speed and executive function.739 L-Phenylalanine vs. D-Phenylalanine: What’s the Difference? L-Phenylalanine is an essential amino acid which means you must get it from food. Or as a supplement. Your body cannot synthesize Phenylalanine on its own.

L-Phenylalanine (LPA) is converted into the amino acid L-Tyrosine in your liver. Once L-Tyrosine crosses the blood-brain barrier, it is converted into L-DOPA. Which is further converted into the neurotransmitters dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline). D-Phenylalanine (DPA) is a synthetic version of, and mirror image of L-Phenylalanine created in the lab. DPA has a different mechanism of action in the body than LPA. D-Phenylalanine (DPA) slows the action of the enzymes carboxypeptidase A or endorphinase and enkephalinase. These enzymes degrade endorphins. Slowing down these enzymes that reduce endorphins can help reduce pain.740 DL-Phenylalanine is a 50/50 combination of L-Phenylalanine and D-Phenylalanine. By combining the two in theory you get the best of both an antidepressant and pain reducer. How does L-Phenylalanine work in the Brain? L-Phenylalanine boosts brain health and function in several ways. But two in particular stand out. 1. L- Phenylalanine decreases depression. L-Phenylalanine is converted into L-Tyrosine which in turn is converted into L-DOPA in the brain. L-DOPA is then used to make the feel good neurotransmitter dopamine. So depression could be the result of not getting enough of the first amino acid (L-Phenylalanine) in the chain of events needed to produce dopamine. In one study done in Germany, 20 depressed patients received from 75-200 mg per day of DLPhenylalanine for 20 days. At the end of the trial 12 of the depressed patients could be discharged without any further treatment. 4 of the patients had a moderate decrease in depressive symptoms. And 4 patients showed no response.741 2. L-Phenylalanine boosts neurotransmitters. L-Phenylalanine turns into L-Tyrosine once taken as a supplement. It then converts into the neurotransmitter dopamine. Dopamine is used to control movement in your body, is fundamental to memory, attention and problem solving. The unused dopamine can then convert into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Norepinephrine is important for attentiveness, emotions, sleeping, dreaming, and learning. Epinephrine drives your ‘flight-or-flight’ response. It’s what prompts your reaction to dangerous circumstances, emergency situations, or in stressful situations or environments. This balance in neurotransmitters is critical to the fully optimized, healthy brain. And why some neurohackers choose L-Phenylalanine to allow the body to make the neurotransmitters it needs. Instead of causing an imbalance by boosting one neurotransmitter over another. A study in Venezuela investigated ADHD and autism, and the implications of amino acids on these neuropsychiatric disorders. 40 subjects affected by autism and 11 with ADHD along with 41 healthy subjects were included in this study.

The researchers found that those with ADHD had decreasing Phenylalanine and increasing glycine which disrupted their inhibitory neurotransmission system. Not enough phenylalanine and increasing lysine was present in those with autism.742 Another study at Ohio State University looked at amino acids in 28 ADHD patients. And found all subjects with ADHD had significantly lower levels of the amino acids phenylalanine, tyrosine, tryptophan, histidine, and isoleucine. The researchers concluded each subject had a general deficit in amino acid transport, absorption, or both.743 How things go bad As we get older, our brain and body chemistry and energy metabolism changes. ↓ Dopaminergic neurons are damaged or die ↓ Neurotransmitter levels decline ↓ Thyroid hormones decline ↑ Stress levels increase ↓ Working memory and mood decline All of these changes are often attributed to aging. But could be a result of dietary and lifestyle choices. Unchecked, they could lead to neurodegenerative diseases like Parkinson’s, a drop in quality of life and depression. L-Phenylalanine benefits L-Phenylalanine can boost levels of the neurotransmitters dopamine, norepinephrine and epinephrine. And can help a sluggish thyroid produce more T4 and T3. L-Phenylalanine can help boost cognition especially in stressful situations. It helps improve decision making, ‘flow state’ and creativity, cognitive flexibility, and working memory. L-Phenylalanine converts into L-Tyrosine which then converts into L-DOPA to produce dopamine. LDOPA is also used to make melanin in your body. This conversion process helps in the removal of neurotoxic quinones. And chelates heavy metals like mercury and lead which can accumulate in and damage neurons. The dopamine that is not used by your brain is available to produce norepinephrine (noradrenaline) which is important for attentiveness, emotions, sleeping, dreaming and learning. L-Phenylalanine may be an effective nootropic when stacked with ADHD/ADD meds like Ritalin or Adderall. It helps supply extracellular dopamine needed to improve the effectiveness of stimulants used to boost the uptake of dopamine in your brain. How does L-Phenylalanine feel?

Keep in mind that L-Phenylalanine is a precursor to catecholamines. So if you’re not ‘low’ on dopamine, norepinephrine or epinephrine - you may not ‘feel’ anything. Many neurohackers report a lift in mood, better focus, concentration, increased energy, and an overall sense of well-being. L-Phenylalanine can help readjust your motivation levels. It can help lower anxiety levels, especially social anxiety. Supplementing with L-Phenylalanine can help bring your blood pressure down if its elevated from a stressful situation or environment. Take it before the stressful event if you can. L-Phenylalanine helps buffer the effects of stimulants like caffeine or amphetamines. It helps potentiate and prolong the effects of Ritalin or Adderall, and reduces the crash. If you’re into athletics or do manual work, you’ll find that supplementing with L-Phenylalanine before a workout or construction job can leave you feeling great afterwards. It may help mitigate many of the effects of acute stress caused by short-term stressors. And L-Phenylalanine helps your body produce L-Tyrosine which helps to produce melanin, so you may find it easier to get a tan while at the beach. The Research Phenylalanine as an Antidepressant Several studies have investigated using Phenylalanine for the treatment of depression. One study published in the journal Arzneimittel-Forschung looked at using DL-Phenylalanine in a small group of patients who failed to respond to popular antidepressants like MAOIs. In this study, researchers worked with 23 patients diagnosed with depression and who had not responded to standard antidepressants. They were given 50 or 100 mg of Phenylalanine daily for 15 days. The researchers found that Phenylalanine completely improved mood in 17 of the patients. Within 13 days of the 15-day trial.744 Another study in the Journal of Neural Transmission studied DL-Phenylalanine use with 20 depressed patients. The subjects were given 75 – 200 mg/day of DL-phenylalanine for 20 days. The study found that 8 patients completely recovered from depression. And another 4 experienced a significant improvement in mood. Another 4 patients saw mild to moderate improvements, and another 4 did not respond to treatment. This study shows that Phenylalanine has considerable antidepressant properties. And is effective for the majority of people suffering from depression.745 Phenylalanine for ADHD Phenylalanine for ADHD seems at first glance as a natural solution for ADHD symptoms. It’s a precursor to the neurotransmitter dopamine which is targeted with stimulants like Ritalin and Adderall. But the very limited clinical evidence tell a different story for practical use.

In this double-blind crossover study, 19 patients with ADD were given DL-phenylalanine or a placebo for 2 weeks. 13 of the ADD patients experienced a significant improvement in ADD symptoms compared to the placebo. And patients saw an improvement in mood. But the patients who did respond to DL-Phenylalanine lost all positive benefits within 3 months. And it’s interesting that a later study with ADHD patients using L-phenylalanine (not DL-Phenylalanine) produced no clinical benefit.746 Another study from 1987 treated 11 hyperactive boys for 2 weeks with D-Phenylalanine. There was no significant improvement or deterioration in behavior.747 There is a modern school of thought that there are several different types of ADD and ADHD. And the symptoms are caused by malfunctions in different parts of the brain depending on the ‘type’ of ADHD. The bottom line is some dealing with ADHD may benefit from supplementing with Phenylalanine. And that DL-Phenylalanine may be the best option. Try it and see if it works for you. Dosage Notes L-Phenylalanine suggested dosage for cognitive benefit is 500 mg up to 3-times per day. You may find your body responds to smaller doses. Or even more if your stacking it with stimulants like ADHD meds. Listen to your body and see how you react. Since L-Phenylalanine is an amino acid, for best absorption and so it’s not competing with other amino acids, take it at least an hour before food. L-Phenylalanine works best on an empty stomach. And take L-Phenylalanine with Vitamin B6 and Vitamin C to further maximize absorption. And give your body what it needs to produce the neurotransmitters dopamine, norepinephrine and epinephrine. L-Phenylalanine is also needed along with L-Tyrosine to synthesize the CoQ10 needed to create fuel within your brain’s mitochondria. Side Effects L-Phenylalanine quickly turns into the non-essential amino acid L-Tyrosine once you take it. So is considered non-toxic and very safe. Most neurohackers don’t have any negative side effects. Important Caution: People with phenylketonuria (PKU), and women who are breastfeeding or pregnant, should not take phenylalanine supplements. Aspartame, found in artificial sweeteners such as NutraSweet, is a source of phenylalanine. People with PKU should not use aspartame. If you are pregnant, ask your doctor about using this artificial sweetener.748 At higher doses there are reports of stomach issues and migraines. Experts say that L-Phenylalanine is toxic in doses above 5000 mg. And higher doses will not give you any added benefit. If you try recommended doses of L-Phenylalanine and do not feel any benefit, then this nootropic may not be right for you. You could try L-Tyrosine or NALT instead.

L-Phenylalanine can increase your thyroid hormones. So if you’re hyperthyroid you shouldn’t use LPhenylalanine. And if you’re taking MAO inhibitors (MAOI’s) like selegiline, Azilect, Marplan or Nardil you should not use L-Phenylalanine. MAOI’s work in your brain and affect neurotransmitters. So using LPhenylalanine in combination with MAOI’s could throw off the delicate balance of neurotransmitters needed for optimal brain health and cognition. And taking L-Phenylalanine with MAOI’s could cause a severe drop in blood pressure which could lead to a heart attack or stroke. Available Forms L-Phenylalanine is available in powder, capsule, and tablet form. Capsules and tablets are usually 500 mg. Phenylalanine is also available as D-Phenylalanine and the 50/50 combined form of DL-Phenylalanine. You may find one form works better for you than another. Ensure you read labels carefully and stick with manufacturers who follow Good Manufacturing Practices (GMP). And are GMP-Certified. Nootropics Expert® Recommendation L-Phenylalanine 500 mg up to 3-times per day I recommend using L-Phenylalanine as a nootropic supplement. Your body does synthesize some L-Tyrosine from phenylalanine which comes from high-protein foods like chicken, fish, almonds, avocados, and bananas. But most of us don’t get enough L-Phenylalanine from our diet. So supplementation will help. And LPhenylalanine is a highly bioavailable, natural form of this amino acid. So you should feel its effects faster. L-Phenylalanine is helpful for most neurohackers to combat stress and sleep deprivation. It’ll boost dopamine, norepinephrine and epinephrine levels. It’s particularly helpful if you take L-Phenylalanine prior to a stressful situation, workout, or physically demanding job. L-Phenylalanine could be helpful to those dealing with ADHD/ADD. It’s a great compliment to stack with stimulant meds like Ritalin or Adderall. L-Phenylalanine will provide the dopamine your brain needs. It will help smooth out and prolong the effects of stimulant meds. And help prevent the associated crash when they wear off. You can safely use up to 1,500 mg per day when stacking with ADHD meds. But dosed throughout your day.

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Phenylethylamine (PEA) Phenylethylamine enhances working memory, executive function, creative flow states, stress reduction, better mood, anti-anxiety and lessens symptoms of ADHD Phenylethylamine (PEA, 2-phenylethylamine, β-phenylethylamine, phenethylamine) is a trace amino acid. Your brain naturally converts L-Phenylalanine into Phenylethylamine (PEA). PEA is not at the top of most nootropic stack choices because its effects are so short-lived. But some neurohackers love PEA for its stimulant and mood enhancing qualities. The most famous promoter of phenylethylamine was Dr. Alexander Shulgin and his wife Anna. Dr. Shulgin published ‘PiHKAL: A Chemical Love Story’ in 1991. PiHKAL is short for “Phenethylamines I Have Known and Loved”. Phenylethylamines are a group of phenethylamine derivatives which contain PEA as a backbone. These derivative compounds are formed by replacing one or more hydrogen atoms in the core structure. This class of PEA compounds include amphetamines, empathogens, stimulants, psychedelics, appetite suppressants, bronchodilators, nasal decongestants, and antidepressants. One of the more famous PEA derivatives is Methylenedioxymethamphetamine (MDMA or Ecstasy or Molly). Dr. Shulgin developed, tested, and published the formulas for 179 different compounds largely based around the structure of PEA in his book PiHKAL. Phenylethylamine (PEA) is a trace amine naturally synthesized from L-Phenylalanine in your brain. Aromatic amino-acid decarboxylase converts phenylalanine to phenylethylamine. This is the same enzyme that converts phenylalanine into dopamine. And it converts it at a rate comparable to the synthesis of dopamine. But PEA is not retained in neuronal vesicles like dopamine is stored. Instead, monoamine oxidase-B (MAO-B) quickly degrades PEA.749 Despite its short half-life, PEA as a nootropic seems to be effective for increasing catecholamine activity by boosting dopamine and norepinephrine.750 PEA can be found naturally in many cacao, algae, fungi, and bacteria as well as clover, beans, peas, and some food products such as Natto and eggs. PEA is also found in chocolate where it is produced during cocao’s fermentation and roasting process.751 PEA binds to C-protein-coupled receptors TAAR1 and TAAR2, receptors reserved specifically for trace amine use.752 These receptors are not used by other major neurotransmitters like they are dopamine or norepinephrine.

The half-life of PEA taken as a nootropic supplement is only 5 – 10 minutes.753 Because it’s quickly degraded by monoamine oxidase-B (MAO-B). Many neurohackers prologue the effects of PEA by using it with a monoamine oxidase-B inhibitor (MAOI) like selegiline (L-deprenyl), hordenine, or Oat Straw. How does Phenylethylamine work in the brain? Phenylethylamine boosts brain health and function in several ways. But two in particular stand out. 1. Phenylethylamine decreases depression. PEA naturally boosts the ‘feel-good’ neurotransmitters dopamine and serotonin in your brain. Studies have shown that depressed patients when tested have lower levels of PEA.754 In fact, some suggest that a PEA deficit may be the cause of depression in the first place. One study had 14 patients with major depression take up to 60 mg per day of Phenylethylamine (PEA) along with 10 mg of selegiline (L-Deprenyl) for up to 50 weeks. Researchers found that “PEA produces sustained relief of depression in a significant number of patients, including some unresponsive to the standard treatments. PEA improves mood as rapidly as amphetamine but does not produce tolerance.”755 2. Phenylethylamine is a mesencephalic enhancer. PEA is considered a mesencephalic enhancer which is defined as “enhancer-sensitive neurons in the brain capable of working in a split-second on a high activity level due to endogenous enhancer substances”.756 This means that PEA stimulates the release of dopamine, norepinephrine, and serotonin in the brain. But unlike stimulant drugs like amphetamine, which release a flood of these neurotransmitters in an uncontrolled manner. PEA instead only increase the amount of neurotransmitters that get released when a neuron is stimulated by receiving an impulse from a neighboring neuron. In other words, the pattern of the neurotransmitter release in not changed. But when the neuron would normally release a neurotransmitter, a larger than normal amount is released.757 The result is nearly instantaneous improvements in cognitive performance, attention, awareness, pleasure, libido, and a sense of well-being. Phenylethylamine is an endogenous (natural or ‘built-in’) amphetamine. This mechanism of action of how prescription ADHD stimulants like Adderall work. And the basis for many Schedule 1 drugs like MDMA758, LSD, mescaline, and (crystal) methylamphetamine.759 How things go bad Phenylethylamine (PEA) is naturally metabolized by monoamine oxidase-B (MAO-B). But as we get older, MAO-B levels rise and suppress healthy levels of PEA.

Low PEA levels have been linked to several neurological diseases. And may result in: ↓ Increased chance of ADHD ↓ Increased chance of addiction ↓ Energy levels decline ↓ Working memory and mood decline ↓ Contributing to Parkinson’s Disease On the other hand, excess levels of PEA have been linked to migraines and paranoid schizophrenia. Phenylethylamine benefits Phenylethylamine (PEA) quickly crosses the blood-brain barrier once you take it. And you feel its effects right away. Activation of TAAR1 receptors inhibit the uptake and induces the release of dopamine, norepinephrine, and serotonin. It’s like turning up the volume of neuron activity. A higher concentration of all of these neurotransmitters increases feelings of pleasure, boosts motivation, improves memory and cognition, and reinforces impulse control. PEA naturally maintains and regulates neuronal activity. Preventing over- or under-stimulation. When working as designed, PEA and other trace amines prevent metabolic dysfunction and neurological disorders. As a neurotransmitter, PEA acts like, and looks similar to amphetamines. And produces effects normally associated with taking a stimulant. But unlike amphetamines, and because PEA is endogenous to the brain, side effects and tolerance are avoided. PEA works in an area of the brain associated with emotions. Resulting in feelings of pleasure, more drive and impulse control, heightened creativity, and better sensory perception. PEA improves libido, social behavior, a sense of wellbeing, and better overall performance. PEA is currently being studied and used for the treatment of ADHD, depression, bipolar disorder, cognitive dysfunction like brain fog and poor concentration. And PEA looks promising for treating addiction and eating disorders. How does Phenylethylamine feel? PEA is rapidly broken down by monoamine oxidase-B (MAO) so unless you stack PEA with a MAO-B inhibitor, don’t expect its effects to last. Most experience a peak within 15 minutes and sustained energy for 30 min. to an hour. If you’re ADHD or ADD, you should see an improvement in mood, attention span, focus and mental clarity. Not quite the same effect you’d get from something like Adderall but with a side benefit of more

sociability. Neurohackers report taking an MAOI (inhibitor) supplement 15 minutes before a PEA dose and the effects should last about 2 hours. And there’s no crash like you’d normally experience with a stimulant. Just a general feeling of well-being once it wears off. Some have reported PEA helped kick the habit of Phenibut or caffeine without going through withdrawal. As a pre-workout supplement, PEA provides a more intense and focused workout. Older neurohackers seem to feel even more benefit when using PEA. Likely because monoamine oxidase levels over-power dopamine the older you get. And using PEA, especially with a MAOI helps restore dopamine and other neurotransmitters that are typically depressed with age. PEA is a great nootropic for study because you should feel less anxiety, fewer panic attacks and less stress. And more motivation, a better mood, easier to maintain focus, and more energy. Some report food cravings subside and it’s easier to lose weight. Phenylethylamine Clinical Research Phenylethylamine as an Antidepressant Depression is the 2nd leading cause of disability among ages 15 – 44. By 2030, the World Health Organization predicts depression will be the leading cause of disability worldwide.760 Selective serotonin reuptake inhibitors (SSRI) are the most popular antidepressant prescribed worldwide. SSRIs work by blocking the serotonin transporter and inhibiting the reuptake of serotonin. Resulting in an increase of serotonin in synapses. But the problem is SSRIs are slow to act. And come with a host of side effects. Phenylethylamine (PEA) may be an alternative to SSRIs. A study done in 2008 showed that PEA alters serotonin transporters by interacting with TAAR receptors. Increasing serotonin levels by preventing their reuptake just like prescription SSRIs. The study suggested that PEA may be a safer treatment for depression than SSRIs.761 Phenylethylamine for ADHD The diagnosis of ADHD has traditionally been done by analysis of symptoms. But measuring PEA levels instead has recently been described as a possible biomarker for diagnosing ADHD.762 This discovery of a relationship between PEA levels and ADHD has excited researchers. Because it will hopefully improve levels of confidence during ADHD diagnosis. And reduce misdiagnosis and overmedication. One study of ADHD children medicated with methylphenidate (Ritalin) had significantly higher PEA levels when using methylphenidate.763

PEA binds to the TAAR1 receptor which alters monoamine transporter function. And leads to the inhibition of the reuptake of dopamine, serotonin, and norepinephrine. Which then increases the concentration of these neurotransmitters in neuron synapses.764 This increase in synaptic concentrations of dopamine can be accomplished by directly blocking the dopamine transporter. Which is how drugs like methylphenidate work to boost dopamine. So if you are ADHD and crave chocolate, it’s likely because cocao supplies PEA. Some naturopaths are beginning to prescribe PEA instead of stimulants like amphetamines or methylphenidate to treat ADHD. Phenylethylamine Recommended Dosage Phenylethylamine (PEA) suggested dosage for cognitive benefit is 500 mg up to 3-times per day. PEA has a half-life of 5 – 10 minutes.765 But the effects of PEA can be extended by using it with a MAO-B inhibitor. If you do use a potent MAOI like selegiline (l-deprenyl) make sure you keep the dose low (i.e. 2.5 mg) or you’re in danger of inhibiting MAO-A as well. More on the “cheese effect” next. Dosing more than recommended is NOT a good idea because you’ll likely feel jittery, irritable, get a headache, feel nausea, and very possibly force your heart rate to dangerous levels. Phenylethylamine Side Effects “Cheese effect”: Phenylethylamine (PEA) is metabolized by the enzyme MAO-B. And when monoamine oxidase (MAO) is inhibited by eating cheese, or any other prescription or natural MAO inhibitor (MAOI), the combination can result in a potentially dangerous increase in blood pressure.766 Studies show that selective MAO-B inhibition does NOT produce this cheese effect.767 Examples of MAO-B selective inhibitors include low-dose selegiline (L-deprenyl), hordenine, Oat Straw, Glycyrrhiza uralensis (Chinese licorice root extract), Phellondendron amurense (Amur cork tree bark), Ferula assafoetida extract (resin), and Psoralea corylifolia (Bu Gu Zhi). Do not use Phenylethylamine (PEA) if you are using a prescription MAOI like Marplan, Nardil, Azilect or Parnate, or have used one in the last 14 days. Do not use PEA if you have phenylketonuria (PKU). Too much PEA can cause irritability, nausea, amplified heart rate, jitteriness, and could be extremely dangerous. Remember, Phenylethylamine (PEA) is an endogenous (natural) amphetamine. And used irresponsibly could produce the same dangerous side effects as anything else in the amphetamine-class of compounds.

Where to buy Phenylethylamine Phenylethylamine (PEA) is available in capsules, tablets, and as a bulk powder. DO NOT make the mistake of buying Phenylalanine instead of Phenylethylamine (PEA). Because it’s NOT the same thing. And is easily overlooked when searching for this nootropic. If you buy PEA in powder-form, you should invest in a capsule machine and make capsules. Because PEA is a particularly nasty tasting nootropic supplement. Nootropics Expert® Recommendation Phenylethylamine 500 mg up to 3-times per day I recommend using Phenylethylamine (PEA) as a nootropic supplement. Your body does synthesize some Phenylethylamine from phenylalanine which comes from foods like beans, cacao, peas, Natto and eggs. But most of us don’t get enough Phenylethylamine from our diet. So supplementation could help. Phenylethylamine is highly bioavailable, and quickly crosses the blood-brain barrier. So you should feel its effects soon after you take it. Phenylethylamine is helpful for most neurohackers to combat anxiety, stress, and sleep deprivation. It’ll boost dopamine, norepinephrine, and serotonin levels. It’s particularly helpful if you take Phenylethylamine prior to a stressful situation, workout, or physically demanding job. And it’s a great nootropic for studying. Phenylethylamine could be helpful to those dealing with ADHD/ADD. It’s a possible substitute to stimulant meds like Ritalin or Adderall for some people. PEA will provide the dopamine your brain needs. And doesn’t produce the stimulant crash when it wears off. PEA works well when stacked with L-Tyrosine (for dopamine), and ALCAR and CDP-Choline (for acetylcholine). PEA is quickly degraded by monoamine oxidase-B. So to prologue its effects, stack it with a low-dose MAOI-B.

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Phenylpiracetam Phenylpiracetam has been shown to boost alertness, cognition, clarity, focus, learning and memory, provides a stimulant-effect, and reduces symptoms of depression and anxiety Phenylpiracetam ((R,S)-2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamide, Phenotropil, Fenotropil, Carphedon, Fonturacetam) is a water-soluble nootropic in the racetam-class of compounds. Phenylpiracetam was created by adding a phenyl group to the original nootropic Piracetam. Russian chemists synthesized Phenylpiracetam in 1983 to boost the physical and mental performance of astronauts during space flight. It’s currently used by Russian cosmonauts on the International Space Station.768 Phenylpiracetam combats physical and mental fatigue. It enhances memory, mood and focus. It facilitates learning and retention, reduces brain fog, increases alertness and boosts physical stamina and tolerance to cold. It turns out that Phenylpiracetam is very effective in boosting athletic performance. It provides significant stimulatory effects and helps you resist cold. Leading to a ban by the World Anti-Doping Agency from use by athletes in the Olympics and other professional sports.769 Russian cyclist Anton Reshetnikov was suspended in 2007 for 2 years from the International Cycling Union for using Carphedon.770 One year earlier (2006), Russian Olympic athlete Olga Pyleleva lost her silver metal for using Carphedon.771 Carphedon is a brand name for Phenylpiracetam. Adding a phenyl group to Piracetam boosts the bioavailability of Phenylpiracetam. It easily crosses the blood-brain barrier and is considered 20 to 60times more potent than Piracetam.772 Neurohackers report that Phenylpiracetam enhances alertness, focus, memory, and learning. It reduces brain fog. And it provides physical stamina and cold tolerance while combating physical and mental fatigue. Phenylpiracetam helps: •

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Prevent Anxiety & Fear: Phenylpiracetam helps reduce symptoms of anxiety and fear. Unlike popular prescription anti-anxiety and anti-depressant drugs, Phenylpiracetam has no sedative action or other adverse side effects associated with these medications.773 Neuroreceptors: Phenylpiracetam increases the density of acetylcholine (ACh), NMDA, GABA and dopamine receptors in the brain.774, 775More receptors mean more binding sites for neurotransmitters that affect memory formation, cognition, sleep and mood. Cerebral Circulation: Phenylpiracetam increases blood flow in the brain. As a derivative of Piracetam, this nootropic has the same mechanism of action when it comes to blood flow. It suppresses the constriction of blood vessels allowing the freer flow of blood. More oxygen and nutrients get to brain cells boosting alertness, cognition, focus and mood.776

Phenylpiracetam is also an effective treatment for epilepsy. This debilitating condition is caused by sudden surges of electrical activity in the brain. This temporary disturbance in messaging systems between brain cells can cause a seizure. Normal brain function gets halted or mixed up. This is where Phenylpiracetam comes in. Phenylpiracetam has been shown in clinical studies to affect Alpha and Beta brain waves.777 Scientists haven’t quite figured out why it works, but Phenylpiracetam has an ‘anti-convulsive’ action in the brain. They did conclude after one clinical trial, “Phenotropil reduced the frequency of seizures and improved cognitive function in the absence of epileptiform EEG abnormalities.”778 Phenylpiracetam is sold as a prescription drug in Russia and several Eastern European countries. In the United States, Phenylpiracetam is sold as an unregulated OTC research compound. How does Phenylpiracetam work in the Brain? Phenylpiracetam boosts brain health and function in several ways. But two in particular stand out. 1. Phenylpiracetam as a stimulant. Phenylpiracetam increases the density of neuroreceptors. Studies have shown it increases the density of acetylcholine (ACh), dopamine, GABA, and NMDA receptors. This translates into more receptors for each of these important neurotransmitters to bind with and boost their effectiveness. The increase in density of neuroreceptors likely accounts for Phenylpiracetam’s stimulant-like properties. Similar to Ritalin or Adderall, this nootropic increases the effectiveness of dopamine in your brain. Increasing alertness, decision-making capability, and cognition. But unlike stimulants like Ritalin and Adderall, Phenylpiracetam does not come with any stimulant-like side effects. You should not experience any fatigue, rapid heartbeat, decreased appetite or irritability. Rather you’ll feel increased stamina, have more physical endurance and get smarter. Just don’t try using Phenylpiracetam if you’re planning on being an Olympic athlete. It was banned several years ago because it’s too effective to be used in professional sports. We don’t want an unfair advantage now, do we? J 2. Phenylpiracetam decreases anxiety and depression. For similar reasons to how Phenylpiracetam works as a stimulant, it can also tame symptoms of anxiety and depression. It increases the density of receptors for acetylcholine (ACh), GABA and NMDA receptors.779 This increase in receptor sites for GABA, choline and glutamate affects levels of the calming neurotransmitters GABA and serotonin in your brain. Phenylpiracetam floods your brain with the neurochemicals you need to chill out.780 How things go bad As we get older, our brain chemistry and metabolism changes. And it seems these changes are affecting younger and younger people.

↓ Recall, reaction time and learning capacity declines ↓ Neurotransmitter levels decline ↓ Density of ACh, dopamine, GABA and NMDA receptors decline ↓ Acetylcholine levels decline ↓ Cerebral blood flow declines ↓ Stamina and endurance decline All of these changes are contributing factors to age-related cognitive decline. Early signs of these effects can be seen in poor decision-making, difficulty learning, and even recalling simple things like an important appointment. But even if you’re not concerned with the signs of aging, Phenylpiracetam can help. Phenylpiracetam benefits Phenylpiracetam is highly bioavailable when used as a nootropic. Once digested it quickly gets absorbed and crosses the blood-brain barrier. Phenylpiracetam modulates neuroreceptors. It’s been shown to increase the density of receptors for GABA, NMDA, dopamine and acetylcholine. More neuroreceptors result in more of each neurotransmitter being able to bind to neurons. And affect alertness, cognition, memory, recall and mood. Phenylpiracetam has a positive effect on physical performance by increasing endurance and reducing physical and mental fatigue. In fact, these effects are so potent that Phenylpiracetam has been banned from professional sports by the World Anti-Doping Agency. Phenylpiracetam has been shown to act as a stimulant. But unlike pharmaceutical drugs, it does not affect your cardiovascular or respiratory system. And does not have the side effects of jitteriness, restlessness or irritability like regular stimulants. Phenylpiracetam is also noted for increasing your threshold to tolerance for cold. How does Phenylpiracetam feel? Many neurohackers say Phenylpiracetam is the strongest nootropic they’ve ever experienced. It’s highly bioavailable and you experience the effects within 30 minutes of taking it. Phenylpiracetam increases concentration, motivation, memory, physical endurance, and tolerance to cold. Learning is quicker and stress is reduced. Learning and processing information becomes easier with Phenylpiracetam. You’re not re-reading sentences and paragraphs trying to understand them.

Short and long-term memory improves. Motor skills improve so you’re typing faster and more accurately. Those dealing with depression report a decrease in depressive symptoms. More confidence helps in social situations and conversations are easier. Productivity rises and you assume a “get it done’ mentality. Procrastination is a thing of the past. Phenylpiracetam is a popular pre-workout supplement. It increases your endurance and reduces both physical and mental fatigue. And if you’re one of the unfortunate ones who live in a cold climate, you’ll find that your tolerance for cold is better. The Research Phenylpiracetam was developed in Russia in 1983. And the majority of research done with this nootropic has been conducted in Russia. Published in Russian medical journals in Russian. So we have limited clinical trial data to draw on. And like many nootropics we rely on nootropic user reviews. The following is two samples of clinical trials I was able to find that have been translated into English. And published in Western medical databases. Phenylpiracetam Improves Cognition A study done by Russian researchers investigated the effects of Phenylpiracetam on cognition. 99 adults aged 40 – 60 suffering from cognition deficits due to surgery or brain trauma were enrolled in this study. Volunteers were given 200 mg of Phenylpiracetam daily for 30 days. The researchers found that those using the nootropic showed a significant improvement in motor coordination, higher brain function, memory, attention and counting. And a reduction in both anxiety and depression.781 Phenylpiracetam Boosts Cerebral Circulation Researchers in Moscow recruited 400 patients suffering from ischemic stroke. This is the most common type of stroke where blood vessels carrying blood to the brain are blocked by a blood clot. Half of the group received 400 mg of Phenylpiracetam daily for a year. The control group got a placebo. The research team found that the group who received Phenylpiracetam experienced a significant restoration in cognitive function and resumed daily activities. Far better than the control group who took a placebo.782 Dosage Notes Recommended Phenylpiracetam dosage is 100 mg twice per day. One Phenylpiracetam dose in the morning, and one in the early afternoon. Don’t use Phenylpiracetam later in the day because its stimulant effect can cause insomnia. You can develop a tolerance to Phenylpiracetam, so consider taking it only on days when you need the extra focus. Or try cycling it one week on and one week off.

Side Effects Phenylpiracetam is non-toxic. So is considered well-tolerated and safe. As with many of the racetams, Phenylpiracetam can cause headaches because it boosts the use of acetylcholine in your brain. Choline supplements like Alpha GPC or CDP-Choline can help you avoid this side effect. Tolerance is a problem with Phenylpiracetam and builds rather quickly. Used to often, it will soon lose its effects. So try using Phenylpiracetam only when you need extra cognitive power, or before a workout. Or try cycling it one week on and one week off to avoid tolerance. Many neurohackers find that stacking Phenylpiracetam with a choline supplement boosts the effect even more with improved memory and cognition. And this is supported in several research studies. Available Forms Phenylpiracetam is sold in tablet, capsule, and powder form. Tablets and capsules are usually 100 mg each. Nootropics Expert® Recommendation Phenylpiracetam 100 mg 2-times per day I recommend using Phenylpiracetam as a nootropic supplement. Your body does not make Phenylpiracetam on its own. So to get its benefits you must take it as a supplement. Phenylpiracetam is especially helpful for those suffering from ADHD or brain fog. This nootropic has a stimulant-like effect similar to that of pharmaceutical stimulants. But without the side effects of increased heart rate, irritability and restlessness. Phenylpiracetam can boost athletic performance. It has been shown to improve physical performance, increase stamina and endurance. And even provides cold-weather resistance. Phenylpiracetam is also particularly useful to students and executives who want to boost alertness, cognition, clarity, focus, learning and memory. This nootropic also has anti-depressant and anti-anxiety benefits. Studies have shown that Phenylpiracetam can be effective in relieving the frequency of epileptic seizures in those dealing with epilepsy. It even compliments some epilepsy medications. You should use Phenylpiracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost the effectiveness of neural acetylcholine, so demands the presence of more choline in your brain. You can safely boost daily intake of Phenylpiracetam to 400 mg. But be aware that tolerance to the effects of this nootropic build quickly. So I recommend using Phenylpiracetam only on days when you

need the extra cognitive power. Or cycle the use of this nootropic one week on, and one week off.

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Phosphatidylcholine (PC) Phosphatidylcholine (PC) is known to repair brain cells and neural connections, boost acetylcholine, and improve alertness, cognition, focus, memory and mood Phosphatidylcholine (PC, or Ptd-Cho) is one of two fatty acids that make up the outer layer of the membrane covering each of the 70 trillion cells in your body. Phosphatidylcholine is also converted in your body through a process called hydrolysis to make up the fatty acids AA, oleic, linoleic, linolenic, and DHA. These fatty acids contribute to the signaling within and between brain cells for long-term potentiation (LTP). LTP is behind the formation of long-term memories. The synthesis of the neurotransmitter acetylcholine (ACh) is largely dependent on the choline provided by Phosphatidylcholine. ACh is critical for cognition, learning and memory. Your brain cells are each encased in a membrane. This bi-lipid layer of two fatty acid tails face each other. The outer layer of each cell contains mostly the phospholipids phosphatidylcholine (PC) and sphingomyelin, while the inner layer contains predominantly phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine. The outer layer of each cell membrane is highly permeable. But the inner layer is much less permeable. These two fatty acid tails are in a constant state of movement, vibrating at millions of times a second. This continual vibration could be considered the ‘backbone of life’. And is the basis of everything that happens in your brain. The amount and type of long-chain fatty acids in your diet affects the composition of these cell membranes. The structure and function of your cells depend on the ideal balance of fats including cholesterol, oleic, palmitic, and stearic fatty acids. And essential fatty acids like Omega 3. Without this proper balance, cell membrane function is compromised. When you don’t have enough phosphatidylcholine, brain cell membranes lose integrity and eventually die. Some phosphatidylcholine is naturally synthesized in your body. We also get PC from some of our food including beef, oysters, eggs, and some vegetables. As a nootropic supplement, Phosphatidylcholine is derived from lecithin found in soybeans and sunflower seeds. Note that lecithin and phosphatidylcholine are NOT the same thing. Plain lecithin is not an efficient source of phosphatidylcholine or choline. As a nootropic, look for as pure of a source of phosphatidylcholine (PC) as you can afford. And you can be sure that our modern diet does not provide the ideal balance of fatty acids (phospholipids) to maintain brain cell integrity. It’s why we experience brain fog, memory loss, slow thinking and poor decision making.

Some progressive health care researchers and practitioners have found that supplementing with phosphatidylcholine (PC) can lessen the symptoms of diseases like MS, diabetes, immune system problems, asthma, and neurodegenerative diseases like Alzheimer’s. How does Phosphatidylcholine Work in the Brain? Phosphatidylcholine boosts brain health and function in several ways. But two in particular stand out. 1. Phosphatidylcholine is needed for long-term memory. The hydrolysis of Phosphatidylcholine (by a process called phospholipase A2-catalyzed hydrolysis) is used to make the free fatty acids AA, oleic, linoleic, linolenic and DHA. These free fatty acids facilitate synaptic transmission by targeting nicotinic ACh receptors using protein kinase C (PKC). This messenger system is needed for long-term potentiation (LTP). Researchers have determined that these fatty acids are critical for learning and memory.783 2. Phosphatidylcholine helps repair neurons. Cholinergic neurons are unique among cells because they serve two functions. PC is a major component of brain cell membranes. And serves as a storage pool for the choline needed as a precursor for acetylcholine (ACh) synthesis. Researchers demonstrated how this works. They incubated human cholinergic cells in the lab. And followed the metabolic link between membrane composition and turnover, and ACh synthesis. And proved that ACh is synthesized from choline derived from the degradation of Phosphatidylcholine. If there is not enough choline available to maintain brain cell membrane integrity, and to synthesize the neurotransmitter acetylcholine, brain cell function breaks down. You experience brain fog, poor memory and decision making. And ultimately leading to neurodegenerative diseases like Alzheimer’s, and other motor neuron disorders.784 How things go bad As we get older, our brain chemistry and energy metabolism changes. This can happen at any age once we enter our adult years. ↓ Brain cell membranes degenerate ↓ Recall, reaction time and mood diminish ↓ Acetylcholine levels decline All of these changes can happen at any age. Our bodies are influenced by the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Phosphatidylcholine can help for age-related cognitive decline, as well as a student looking to do better in school. Phosphatidylcholine benefits Phosphatidylcholine (PC) has been around as long as humans have walked this planet. PC is a critical

component of the top layer of the membrane surrounding each one of the cells in your body. And yet some are talking about Phosphatidylcholine as the “New Wonder Drug”. How could this be? Turns out that PC is a fatty acid. As are many of the fats we consume in our modern diet. Long-chain fatty acids affect the composition of our cell membranes. When we eat bad fats our cell membrane fluidity is affected, ion channels disrupted, hormones, regulation of neuroreceptors, signaling and other signaling chemicals are affected. Incorrect amounts or types of long chain fatty acids can lead to a cascade of serious health and cognition problems. The easiest and simplest way to correct many of these cognition problems is to supplement with Phosphatidylcholine as a nootropic. You’ll feel better as cells are repaired. Digestion issues could be eliminated or minimized. And brain fog, cognition and memory problems could become a non-issue. How does Phosphatidylcholine feel? If you eat a perfectly healthy diet and are in optimal physical and mental health, using Phosphatidylcholine may not do anything for you. But if you’re like most in the Western world relying on fast food, processed food and other unhealthy lifestyle habits, then PC may help. Neurohackers report that supplementing with Phosphatidylcholine lifts brain fog, improves working memory and boosts alertness. Others say it helps them prevent anxiety and panic attacks. Mental clarity is improved, and energy levels rise. Ray Kurzweil, the famous inventor, and futurist, gets phosphatidylcholine intravenously once a week at his health clinic. His theory is that this will rejuvenate all his body’s tissues.785 The Research A double-blind study in California with 80 college students investigated the effect of Phosphatidylcholine on memory. The students received a placebo or either 10 or 25 grams of Phosphatidylcholine (PC). 25 grams of PC was estimated to supply about 3.75 grams of choline. Memory was tested at 60 and 90 minutes after taking PC. The researchers recorded a significant improvement in memory after 90 minutes, and only a slight improvement after 60 minutes. This 1993 study was the first to test the relationship between a single dose of Phosphatidylcholine on memory in healthy human subjects.786 Phosphatidylcholine Prevents Brain Cell Death Streptococcus pneumonia is the most common cause of bacterial meningitis. And is the most common cause of death from pneumonia. If it doesn’t kill you, it can cause paralysis, mental retardation and

learning disorders. In humans, it’s your hippocampus neurons that are the first to die as a result of meningitis. Cell death is officially called “apoptosis”. But I’m using cell death to drive a point home. Phosphatidylcholine (PC) is an essential component of your cell membranes. And a deficiency of PC, either from chemicals or bad nutrition leads to cell death. And the first to go are your hippocampal neurons. The same neurons used for learning and memory. Researchers in Tennessee found that a variety of brain cells die after you get pneumonia. Because it interferes with Phosphatidylcholine synthesis. And apoptosis inhibitors can’t even stop this cell death from happening. The research team determined that the only way to prevent cell death from pneumonia infection was supplementing with Phosphatidylcholine. Even after the infection set in. The researchers concluded that supplementing with Phosphatidylcholine was the best way to prevent what they called an “apoptotic cascade”. And the best therapeutic intervention.787 Phosphatidylcholine Improves Memory Studies on the effect of Phosphatidylcholine on memory are limited. So researchers in Japan decided to remedy this lack of data by testing PC in mice with dementia. They administered PC to mice with dementia and to normal mice. And compared differences in memory, choline and acetylcholine concentration, and choline acetyltransferase (ChAT) activity. ChAT is the enzyme responsible for the synthesis of acetylcholine in the brain. The researchers found that giving phosphatidylcholine for 45 days to mice with dementia improved memory. And generally increased brain choline and acetylcholine concentrations to or above the levels of the normal control mice. The research team concluded that phosphatidylcholine increases brain acetylcholine concentration and improves memory.788 Dosage Notes Recommended Phosphatidylcholine dosage is 1,200 mg to 5 grams per day. And divide your total daily dose into 2 or 3 equal doses and dosed throughout the day. To enhance bioavailability and boost absorption, take PC 30 minutes before a meal. Do not take Phosphatidylcholine with acetylcholinesterase (AChE) inhibitors since this combination may excessively increase acetylcholine (ACh) levels and potentially cause cholinergic side effects. AChE inhibitors include donepezil (Aricept), tacrine (Cognex), rivastigmine (Exelon) and Huperzine-A. Side Effects Phosphatidylcholine is naturally produced in your body and is considered well tolerated and safe. PC is

not toxic. Some may experience sweating, stomach upset and diarrhea. Particularly if you’re already high in choline. Available Forms Phosphatidylcholine is sold in tablet, capsule, liquid and powder form. Capsules can run from 420 – 1,300 mg each. 500 mg of Phosphatidylcholine in powder form is equivalent to 2-level 1/8 tsp scoops. Phosphatidylcholine is sometimes used interchangeably with “lecithin,” although the two are different. Choline is a component of phosphatidylcholine, and is also a component of lecithin. Although closely related, these terms are not the same. Nootropics Expert® Recommendation Phosphatidylcholine 1,200 mg to 5 grams per day I recommend using Phosphatidylcholine as a nootropic supplement. Phosphatidylcholine helps build and repair cell membranes. And is found in every one of the 70 trillion cells in your body. You can get Phosphatidylcholine from some of the food you eat. But Phosphatidylcholine is only found in foods like beef, eggs, oysters, and some vegetables. PC levels decline as you age, and you are unlikely to get nearly enough through diet. So to get its benefits you must take it as a nootropic supplement. Phosphatidylcholine is vital to maintaining optimal brain health. And has been shown to increase cognitive energy, boost brain function, enhance communication between neurons, and protect neural membranes from free radical damage. I suggest starting with a dose of at least 1,200 mg daily. And Phosphatidylcholine is a great compliment to a stack including any nootropic from the racetam-family. Anything that causes an increase in uptake of acetylcholine in your brain. You need to provide your brain with the choline it is demanding. Or it starts cannibalizing your own brain cells to make more acetylcholine. Signs that you’re lacking adequate choline are headaches. Use Phosphatidylcholine at a ratio of 1:4. For example, 250 mg of Phosphatidylcholine to 1,000 mg of Aniracetam. If you have liver damage like cirrhosis, you may want to increase the dose up to 4.6 grams per day for liver repair.

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Phosphatidylserine (PS) Phosphatidylserine (PS) is known to improve alertness, attention, cognition, memory, recall and mood, lower anxiety, and help you lose weight Phosphatidylserine (PS) is a phospholipid component of brain cell membranes. The membrane is the outer casing surrounding each cell. PS plays a vital role in cell-to-cell signaling in the brain. And is needed to maintain the fluidity of all cell membranes. Phosphatidylcholine (PC) is the most abundant phospholipid in the brain. Followed by a slightly lesser amount of Phosphatidylserine (PS). PC is in the outer layer of brain cell membranes, and PS is part of the inner layer. Both are critical to maintaining optimal cognitive health. PS is synthesized from PC in the brain by exchanging the base head group with a serine. Phosphatidylserine (PS) supports the formation and sending of neural signaling within neurons. And across synaptic junctions that link one neuron with another. This cellular communication contributes to how we form memories. Phosphatidylserine (PS) also helps produce nerve growth factor (NGF) that ensures healthy neurogenesis. And PS even assists in building mitochondria which are the energy source in every one of your brain cells. When your brain cell membranes are healthy, they are malleable, fluid and flexible. But by the time we reach our 20’s, phospholipids including Phosphatidylserine (PS) start declining. This outer casing starts to harden. And attention, concentration, memory, mood and learning begin to suffer.789 The good news is you can prevent this cellular damage from happening. The amount and type of longchain fatty acids in your diet affects the composition of these cell membranes. The structure and function of your cells depend on the ideal balance of fats including cholesterol, oleic, palmitic, and stearic fatty acids. And essential fatty acids like Omega 3. Without this proper balance, cell membrane function is compromised. But our typical modern diet does not provide the ideal balance of fatty acids (phospholipids) to maintain brain cell health. It’s why we experience brain fog, memory loss, slow thinking and poor decision making. You naturally get Phosphatidylserine (PS) from foods like cow brains, pig spleen and chicken hearts. So there must be some merit to the saying, “Eat brains and get smarter”. Unfortunately, not many of us include organ meat as part of our daily meal plan. So the best way to maintain healthy levels of Phosphatidylserine (PS) in your brain is taking PS as a nootropic supplement. PS was originally made from bovine (cow) brains. But with the mad cow disease scare, PS supplements are now made from extracts of soy or sunflower lecithin.

Phosphatidylserine (PS) is arguably one of the most effective and important nootropics we have available today. PS keeps our brain cells healthy. And has a reputation for improving alertness, attention, cognition, memory, recall and mood. How does Phosphatidylserine work in the Brain? Phosphatidylserine boosts brain health and function in several ways. But two in particular stand out. 1. Phosphatidylserine is needed for memory. PS stimulates the brain chemicals that boost neural signaling for quick, clear thinking. In fact, Phosphatidylserine is one of the most effective memory boosters known. PS has been shown that it can slow, halt and even reverse the progression of age-related cognitive decline. One study with 149 patients meeting the criteria for age-associated memory impairment were given 100 mg of Phosphatidylserine or a placebo for 12 weeks. The patients who received PS showed improved performance on tests related to learning and the memory tasks of daily life. The study concluded that PS was a promising candidate for treating memory loss later in life.790 2. Phosphatidylserine helps repair neurons. PS works in concert with DHA (Omega-3) to protect brain cells from damage. And boost neuronal survival. You brain is made up largely of DHA fat. The kind of fat you get from supplementing with Omega-3’s. And a decrease in DHA content in the brain results in cognitive impairment. Studies show that Alzheimer’s Disease is associated with lower Omega-3 fatty acid intake. Researchers in Canada looked at samples provided by the Memory and Aging Project. And found a significant difference in plasma fatty acid profiles of those with Alzheimer’s, mild cognitive impairment and those with perfectly healthy brains. The team found that DHA in Phosphatidylserine in both disease categories was 12-14% lower than those of healthy brains. They concluded that Alzheimer’s Disease is associated with lower DHA and Phosphatidylserine.791 Trials and clinical studies like these provide plenty of motivation to supplement with Phosphatidylserine and DHA. It will help you ward off neurodegenerative disease. DHA and PS for an optimized brain. How things go bad As we get older, our brain chemistry and energy metabolism changes. This can happen at any age once we enter our adult years. ↓ Brain cell membranes lose fluidity ↓ Neurotransmitter signaling declines ↓ Recall, reaction time and mood diminish

↓ Memory declines All of these changes can happen at any age. And starts as early as our 20’s. Our cell membranes are influenced by the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Phosphatidylserine (PS) can help for age-related cognitive decline, as well as a student looking to do better in school. Phosphatidylserine benefits Phosphatidylserine (PS) makes up about 15% of the total phospholipid pool in your brain. PS is located mainly in the internal layer of your brain cell membranes. PS is involved in governing membrane fluidity, and the regulation of all activity going on in that brain cell. PS interacts with cellular proteins, modulates the activity of neuroreceptors, enzymes, ion channels and signaling molecules. Supplementing with Phosphatidylserine improves brain function that tends to decline with age. Healthy brain cell membranes support neuroplasticity so neurons can form the connections needed to convert new experiences into memories. Phosphatidylserine helps lower cortisol and ACTH levels during intense exercise.792 PS is even effective in relieving stress. And putting you in a better mood during exams.793 Many clinical trials with PS have shown improvements in working- and long-term memory, recall, logic and even speech. Attention span increases while using PS. And motivation, socialization and initiative all increased when using Phosphatidylserine as a nootropic. How does Phosphatidylserine feel? Neurohackers report that using Phosphatidylserine (PS) as a nootropic: • • • • • • • • • • • • • •

Boosts energy levels Improves alertness Less brain fog Better memory Logical thinking improves Concentration is better Clarity of thought Weight loss Easier to remember names, phone numbers, tasks, etc. Mood improves Anti-anxiety Lowers cortisol Relieves insomnia Vivid dreams

There are reports that PS helps with Tourette’s Syndrome. Phosphatidylserine (PS) a great compliment to ADHD meds. PS helps tame the symptoms of ADHD. And doesn’t interfere with popular stimulants like Ritalin and Adderall. You may even be able to cut back on the ADHD meds once Phosphatidylserine builds up in your system. The Research Phosphatidylserine Reduces Beta Brain Waves Beta brain waves have the most rapid pattern of all the brain waves produced in your brain. Beta waves are associated with concentration, arousal, alertness and cognition. But it would be unpleasant to be in a constant state of arousal. This study in Germany gave 16 healthy subjects Phosphatidylserine (PS) for 42 days. The team tested brain wave patterns before supplementation. And again in 42 days. The main finding in this study was that chronic Phosphatidylserine supplementation significantly decreases Beta brain waves. And the results showed that the PS group were connected to a more relaxed state compared to the controls.794 Phosphatidylserine Reduces Stress Studies have shown that Phosphatidylserine blunts the release of cortisol in response to exercise stress. And PS improves mood. In this study, researchers at the University of Wales Swansea gave young adults 300 mg of Phosphatidylserine each day for a month. The study resulted in these young adults feeling less stressed after doing a stressful arithmetic task. And they were in a better mood. The researchers concluded that PS supplementation improves mood and reduces stress even in healthy, young people.795 Phosphatidylserine Improves Cognition in Athletes Phosphatidylserine is found in the cell membranes of most animals and plants. PS has been shown to reduce stress and increase performance in runners, cyclists and golfers. This double-blind, placebo-controlled study was conducted to study the effects of PS on cognitive function, mood and endocrine response before and after intense exercise. 18 lower body, resistance-trained male college athletes took Phosphatidylserine for 14 days, or a placebo. Following 14 days of supplementation, participants performed an acute bout of lower body resistance training. Mood and cognitive function were measured before, 5 minutes after and 60 minutes after exercise. And blood samples were drawn prior to, 5, 15, 25, 40 and 60 minutes after exercise. Blood was tested for cortisol and testosterone. The researchers found that PS significantly increased cognitive function prior to exercise. And PS prevented both mood and hormones from being negatively affected prior to and following resistance

exercise.796 Phosphatidylserine Reduces Symptoms of ADHD Researchers in Japan conducted a randomized, double-blind, placebo-controlled trial with 36 children aged 4 – 14 years. The kids were diagnosed with ADHD but had not received any conventional ADHD treatment prior to the trial. The children received 200 mg of PS or a placebo daily for 2 months. The team recorded the children’s ADHD symptoms, short-term and working memory, and mental performance. The team found that Phosphatidylserine significantly improved ADHD symptoms and short-term memory. ADHD symptoms that were reduced included inattention, short-term memory, and impulsivity. The placebo group saw no improvement during the trial.797 Another study with 200 ADHD children looked at the effects of Phosphatidylserine combined with Omega 3’s for 30-weeks. The key finding of this trial was a significant reduction in the restlessness/impulsive scale and an improvement in emotions. The researchers concluded that Phosphatidylserine with Omega 3 may reduce ADHD symptoms in children with ADHD. And it was especially effective in a subgroup of hyperactive-impulsive, emotionally, and behaviorally dysregulated ADHD children.798 The bottom line is that if you have Adult ADD like I do, or you have children with ADHD or ADD, consider 200 mg of Phosphatidylserine for a couple of months before going with Adderall or Ritalin. And add in some Omega 3’s for good measure. Phosphatidylserine Improves Memory Several studies have shown that using Phosphatidylserine as a nootropic to boost memory works well both for age-related cognitive decline as well as more serious diseases like Alzheimer’s and dementia. A double-blind, placebo-controlled trial in Tel Aviv worked with 18 healthy elderly volunteers with age related cognitive decline. The volunteers took 100 mg of Phosphatidylserine 3-times per day for 12 weeks. They were evaluated at the start of the trial, at 6 weeks of treatment and at the end of the trial. All but two of the volunteers showed significant improvement in memory from using Phosphatidylserine (PS). Memory and cognition improved in the first 6 weeks of PS use. And continued to get better until the end of the 12-week trial.799 Another trial with 51 Alzheimer’s patients using 100 mg of Phosphatidylserine for 12 weeks showed that PS may be a promising candidate for the early stages of Alzheimer’s Disease.800 Dosage Notes Recommended Phosphatidylserine (PS) dosage is 100 mg 3-times per day. If you’re concerned about Genetically Modified Organisms (GMO) like I am, make sure you find Phosphatidylserine (PS) that is non-GMO. Because most PS is derived from the lecithin of soybeans.

And oddly enough a manufacturer may use both GMO and non-GMO. And not have it marked on the packaging. I’m aware of at least one supplement maker who offers non-GMO PS in their 120-count bottles. But their 60-count bottles are made with GMO soybean lecithin. Do your research. Even better is find Phosphatidylserine (PS) that is made from non-GMO sunflower lecithin. Especially if you’re allergic or react to soy. Side Effects Phosphatidylserine (PS) is naturally produced in your body and is considered well tolerated and safe. PS is non-toxic. Some may experience insomnia or stomach upset at higher than recommended doses. Medications for Alzheimer’s may interact with Phosphatidylserine because these drugs are often Acetylcholinesterase (AChE) inhibitors. An AChE inhibitor will increase the amount of acetylcholine (ACh) in your brain. And since PS increases ACh, you may end up with too much acetylcholine. Available Forms Phosphatidylserine is sold in tablet or capsule form. Capsules can run from 100 to 300 mg each. Plain PS was originally sourced from cow brains. But since the mad cow disease scare, most PS supplements are now made from soybean lecithin. Enzymotec makes a unique form of Phosphatidylserine called Sharp PS®. It is made from vegetable sources that are not soy-based and is non-GMO. Several supplement makers offer this branded form of PS which they license from Enzymotec. Nootropics Expert® Recommendation Phosphatidylserine 100 mg 3-times per day I recommend using Phosphatidylserine (PS) as a nootropic supplement. Phosphatidylserine (PS) is arguably one of the most effective and important nootropics we have available today. PS keeps our brain cells healthy. And has a reputation for improving alertness, attention, cognition, memory, recall and mood. PS helps lower cortisol which can help with insomnia. And provide you with a stress-free workout in the gym or on the court. Phosphatidylserine (PS) clears brain fog, boosts energy levels, helps alertness, and provides clarity to your thought process. You can get Phosphatidylserine from food. But the highest concentrations of PS are found in organ meats like cow brains and pig spleen.

PS levels decline as you age starting in your 20’s. And you are unlikely to get nearly enough through diet. So to get its benefits you should take it as a nootropic supplement. I suggest starting with a dose of PS at 100 mg 3-times per day. Dosing should not exceed 500 mg per day. And there is little benefit to overdoing it with Phosphatidylserine (PS).

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Picamilon Picamilon is known for having a strong anti-anxiety effect while boosting concentration, focus, memory and motivation, and lowering blood pressure Picamilon (nicotinyl-y-aminobutyric acid, or N-nicotinoyl-GABA) is a derivative of the inhibitory neurotransmitter GABA and nicotinic acid (niacin or Vitamin B3). Russian scientists conducted a lot of research into GABA and cognitive health in the 1960’s and 70’s. The nootropics community has benefited from this research. It was the Belgians who started the development of the racetam-family of nootropics. And not too long afterwards, Russian scientists continued the research on GABA-derived compounds and gave us Phenibut and Picamilon. GABA’s role is to keep glutamate, the primary excitatory transmitter, from overwhelming your brain. Too much glutamate can cause a seizure, and too little GABA can put you in a coma. A healthy brain maintains a critical balance of GABA and glutamate. GABA acts like a “brake” on neuron circuits during stress. Low GABA levels can result in anxiety, insomnia, poor mood and restlessness. Clinical studies show that boosting GABA with a supplement like Picamilon relieves anxiety, stress, and boosts the production of alpha brain waves.801 If GABA is optimized in your brain you’ll feel focused, relaxed and stress-free. But the big challenge for cognitive health is trying to boost GABA levels in the brain. GABA cannot cross the blood-brain barrier on its own. It needs help to carry it across this barrier. Including Vitamin B3 (niacin) in the Picamilon formula helps GABA to cross the blood-brain barrier. And the reason why some neurohackers prefer Picamilon when the goal is to raise GABA levels in the brain. Picamilon is unique among GABA boosters because it can boost cerebral circulation as well.802 It increases cerebrovascular activity better than Piracetam and Vinpocetine. It’s even better at boosting blood flow than prescription vasodilating agents like cinnarizine, papaverine, and xanthinol niacinate. So when using Picamilon to boost GABA, you enhance cerebral circulation, and lower blood pressure. GABA even stimulates the pituitary gland to secrete Human Growth Hormone. And helps produce endorphins that make you feel good after a workout or sex. As a nootropic, when you use Picamilon to normalize GABA levels you’ll improve blood flow to and within your brain. And you’ll experience a reduction in anxiety, insomnia, nervousness, restlessness and stress. Picamilon exhibits the properties of a tranquilizer with a stimulating component. But unlike tranquilizer drugs, Picamilon does not induce muscle relaxation, drowsiness, or lethargy.

How does Phenibut Work in the Brain? Phenibut helps brain health and function in several ways. But two in particular stand out. 1. Picamilon boosts cognition. Picamilon is a derivative of GABA and niacin. And easily crosses the blood-brain barrier. GABA on its own cannot cross this barrier unless paired with a dedicated carrier.803 When niacin is bonded to GABA the molecule easily enters the brain. Once in the brain, Picamilon separates back into niacin and GABA. GABA works by preventing neural signaling associated with anxiety from reaching other neurons. It does this by attaching to the receptors that would otherwise excite those neurons. Over-stimulating neurons in certain areas of your brain is what causes anxiety-related symptoms. Studies have shown this unique combination of niacin and GABA affect the regulation of neurotransmitters in the brain. Picamilon was shown in one study on Parkinson’s disease to normalize serotonin and dopamine content, and dopamine uptake in the brain.804 2. Picamilon improves cerebral blood flow. Picamilon is more effective than Piracetam and Vinpocetine in improving blood flow to cerebral vessels in the brain. It easily crosses the bloodbrain barrier to protect neurons against the effects of diminished oxygen flow. Improving cognitive function. Picamilon separates into niacin and GABA once it crosses the blood-brain barrier. Niacin acts as a vasodilator relaxing blood vessels and allowing the freer flow of blood in the brain. Picamilon is often prescribed in Russia for treatment of migraine headaches. A study published in Nutrition Journal reviewed clinical trials from 1990 – 2004 looking at studies using niacin to treat migraines, and other tension-type headaches. The conclusion from this review showed niacin’s effectiveness for its vasodilatory properties in increasing cerebral blood flow. And its ability to improve mitochondrial energy metabolism.805 The result is fewer migraines and less headaches when using a nootropic containing niacin. How things go bad Low levels of GABA and poor cerebral circulation are associated with a variety of health problems. ↑ Anxiety806, panic attacks, stress and insomnia ↑ Muscle spasms, hypertension, convulsion, Tourette’s Syndrome, and epilepsy ↓ Neurotransmitters decline ↓ ATP energy levels decline starving mitochondria in brain cells When your neurotransmitters, including GABA, are in balance, you feel motivated, productive, and energetic. And you feel calm and relaxed during downtime. When GABA levels are low you feel filled with dread, you’re constantly worried, you have racing

thoughts, and you’re frequently late and disorganized.807 Many people in this GABA-slump resort to high carbohydrate foods, and drugs or alcohol to relax. Picamilon benefits Picamilon is an analogue of GABA and nicotinic acid (Vitamin B3 or niacin). The addition of niacin allows GABA to cross the blood-brain barrier (BBB). We need adequate GABA levels in our brain because it’s an inhibitory neurotransmitter. When we raise GABA levels by supplementing with Picamilon, we help keep glutamate in check. Glutamate is your body’s most abundant excitatory neurotransmitter. Which is responsible for attention span, brain energy, learning ability, memory, and staying awake. So GABA is calming and glutamate is stimulating. And they must be in balance with each other for optimal cognitive health. An imbalance of these two neurotransmitters can cause fibromyalgia, chronic fatigue syndrome, poor memory and cognition, anxiety and depression. But when these two neurotransmitters work together efficiently, you feel relaxed with no stress or feelings of anxiety. And you get a more restful night’s sleep. The addition of nicotinic acid in the Picamilon formula helps improve cognition even more. One study with 96 healthy volunteers was done to determine the effects on memory with nicotinic acid. The study found that nicotinic acid (niacin) enhanced cell metabolism and oxygen supply in the brain. Resulting in an improvement in short-term and long-term memory.808 Adding Picamilon to your nootropic stack can help bring GABA and glutamate back into balance. How does Picamilon feel? When you balance GABA levels in your brain, you feel relaxed and calm. But many neurohackers who try using GABA as a supplement don’t feel the effects. Because the GABA molecule is too large to cross the blood-brain barrier.809 Note: If you do feel the calming effects of supplementing with GABA within a ½ hour of taking it, it may mean you have a “leaky” blood-brain barrier. Not a good thing.810 Because if GABA can get through, all kinds of nasty stuff can get through too. Including toxins, undigested food particles and anything else in your blood stream that shouldn’t be in your brain. But here were talking about increasing our GABA levels using Picamilon. Neurohackers report that adding Picamilon to their stack relieves anxiety “better than Xanax”. There is less stress and they feel more relaxed. Picamilon also offers a stimulant effect providing mental clarity, dreams can be vivid, and it’s not sedating like Phenibut.

Social functions could get some help with Picamilon. You could feel less inhibited, speak freely and feel more confident. Picamilon generates a calm focus without making you drowsy. Some neurohackers maintain that the ‘magic’ with Picamilon is in the nicotinic acid. And I’d have to agree with this observation. It’s what provides the stimulant-effect and gives you an energized type of calmness. The cognitive benefits of niacin are considerably understated in the nootropics community. Just check out the research and studies in my NADH chapter for more on the magic of niacin. The Research Nearly all the research with Picamilon has taken place in Russia. It’s published in Russian journals in Russian. Most of these trials are not indexed in international or US medical databases. I won’t get into the politics of this type of behavior here in this book on nootropics and brain optimization. I’m here to educate and collate information for you on nootropics to help cognitive health. The sources I have been able to find shows Picamilon extensively studied in animals and humans. And has been shown to act like a tranquilizer without the sedative effects of muscle relaxation, drowsiness, or lethargy. The studies show Picamilon decreases anxiety, fear, irritability and symptoms of emotional stress. It inhibits aggression and restores physical working capacity after stressful work. Picamilon has been proven to prevent forgetfulness, enhance memory, recall and improve mood. It decreases headaches, dizziness and tinnitus. It increases mental and motor activity in patients with anxiety and depression. Picamilon has been shown to prevent or suppress diabetic neuropathy811, and alleviate the effects of alcohol withdrawal. It helps glaucoma, retinal and optic nerve damage812. And helps those with neurologically-based urinary problems. Here we talk about how Picamilon, nicotinic acid and GABA can affect your cognition and overall health. This research supports the idea of using Picamilon to raise GABA and niacin levels. And the cognitive benefits can have a profound effect on your quality of life. Picamilon increases dopamine uptake Reports by neurohackers repeatedly show that Picamilon provides a ‘calm focus’ without making you drowsy. And this study, done in the Ukraine gives us a clue on how this works. This study was done with Parkinson’s patients. It’s well know that serotonin and dopamine content and dopamine uptake by neurons in Parkinson’s Disease is decreased. This research found that Picamilon normalized dopamine uptake in Parkinsonism. And that Picamilon is “involved in the regulation of brain neurotransmission under experimental parkinsonism and can be useful in treatment of Parkinson’s disease”.813

Picamilon boosts brain cell mitochondria function We know from our research on Nootropics Expert that NADH boosts ATP energy production within brain cell mitochondria. And this “energizing” effect that’s often spoken of when using Picamilon comes at least in part from its niacin component. This study done on one-month old rats looked at trauma of the brain. The researchers studied oxidative damage done on brain mitochondria 1, 4, 7 days and 4 weeks after the trauma. The young rats were given several different nootropics to see the effect on the rat’s mitochondria. And they concluded that Picamilon had a protective effect on the function of brain mitochondria during the trauma.814 Picamilon increases blood supply, oxygen saturation and blood circulation in the brain.815 This boost in blood flow816 brings the nutrients and oxygen need to create ATP within brain cell mitochondria. Dosage Notes The recommended daily starting dosage of Picamilon for anxiety is 50 mg 2 or 3 times per day. If you’re looking for a stimulatory effect, you can safely increase your dose to 100 mg 2 or 3 times daily. Side Effects Picamilon is considered safe when taken in normal recommended doses. Picamilon has not been shown in clinical trials to produce any allergic or toxic effects. The only side effects noted were headache, dizziness, and nausea. And nearly always when taken above recommended doses. At higher doses Picamilon can lower blood pressure. So if you are already on blood lowering medication, or have an issue with low blood pressure, you should not use Picamilon. Available Forms Picamilon as a nootropic supplement is available in powder, tablet, and capsule form. But very few major supplement retailers sell the tablet or capsule form of Picamilon. If you choose the buy bulk Picamilon powder from a vendor, make sure you ask for a genuine Certificate of Analysis to verify its authenticity. Nootropics Expert Recommendation Picamilon 50 – 100 mg 2 or 3 times per day. I recommend using Picamilon as a nootropic supplement if you’re feeling anxiety or stress. And to calm or keep in check the stimulatory effects of some nootropics. Your body does make GABA on its own from glutamate in your brain. Most healthy people have an adequate supply of GABA. But if you’re dealing with anxiety or stress and need some extra help in calming things down, Picamilon can help.

Picamilon is particularly helpful if you’re dealing with anxiety. Some neurohackers report that Picamilon is as effective in dealing with anxiety as many prescription anti-anxiety meds. Picamilon exhibits the properties of a tranquilizer with a stimulating component. But unlike tranquilizer drugs, Picamilon does not induce muscle relaxation, drowsiness or lethargy. In addition to its calming effects, Picamilon may help improve your memory, recall and concentration. There is no reported added benefit to doses higher than those recommended. In fact, the reverse appears to be true. Lower recommended doses have more of a calming and cognitive effect for most people.

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Pine Bark Extract Pine Bark Extract has been shown to improve ADHD, decision-making, concentration, focus, memory, and mood Pine Bark Extract is a standardized extract of French maritime pine bark. This pine tree (Pinus pinaster) is native to the Mediterranean region. The extract of maritime pine bark called Pycnogenol contains 65 – 75% proanthocyanidins (procyanidins).817 Oligomeric proanthocyanidins (OPCs) are also found in high concentrations in wide variety of plants. Including apple, pear, grapes, chocolate, wine, and tea. Professor Jacques Masquelier of the University of Bordeaux, France was the first to study oligomeric proanthocyanidins (OPCs). The professor got his inspiration from reading about Jacques Cartier’s 1534 expedition up the St. Lawrence River. Cartier’s crew were trapped in the ice and dying of scurvy. The crew survived after native Iroquoians gave them a tea brewed from the bark and needles of pines growing by the river. Prof. Masquelier speculated pine extracts in the tea contained vitamin C and flavonoids that helped the crew’s recovery.818 In 1948, the professor isolated the first OPCs from peanut skins. And patented his extraction method of isolating OPCs from pine bark in 1951. In 1965, research was begun by Charles Haimoff, the founder of Horphag Research in Berlin. He developed a water-soluble extract of the same French maritime pine tree. Calling his extract Pycnogenol®. Throughout this chapter I may refer to Pine Bark Extract or Pycnogenol. Assume I’m talking about the same extract. As a nootropic, Pine Bark Extract is used primarily to increase cerebral blood flow. Other uses include using Pine Bark Extract for the prevention of neurodegenerative diseases like Alzheimer’s or Parkinson’s, ADHD, high blood pressure, osteoarthritis, chronic pain, and erectile dysfunction (ED). On a molecular level, Pine Bark Extract helps with oxidative stress, membrane damage, DNA damage, inflammation, and glycation. Here we’ll investigate Pine Bark Extract’s value as a nootropic to optimize cognition. Pine Bark Extract helps: •

Neurotransmitters. Pine Bark Extract helps prevent decreases in dopamine and norepinephrine. And the glutathione (GSH) and GSH-disulphide reductase (GSSG-R) ratio. Neurotransmitter

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problems which contribute to hyperactivity in ADHD.819 Cerebral Circulation. Pine Bark Extract helps boost blood flow to and within your brain. By increasing nitric oxide which helps dilate blood vessels. And helping repair and maintain the health of the lining of blood vessels. Neurodegenerative Disease. Pine Bark Extract prevents accumulation of oxidatively damaged proteins. And may reduce the risk of diseases like Parkinson’s, Alzheimer’s, and Huntington’s.820 DNA damage – Pine Bark Extract helps reduce DNA damage caused by oxidation821 Inflammation – Pine Bark Extract inhibits proinflammatory gene expression.822 The type of inflammation implicated in diseases like Alzheimer’s. Glycation – Glycation is caused when sugar molecules bond to protein and fat molecules. Triggering oxidation and inflammation. Pine Bark Extract prevents glycation by lowering blood sugar levels.823 Membrane damage – Damage to neuron membranes disrupt neuronal communication and structure. Pine Bark Extract protects brain cell membranes from free radical damage, chelating heavy metals, restores membranes, and prevents their rupture and leakage. Helping to prevent stroke.824 Oxidative stress – Free radicals damage DNA and brain cell membranes by causing inflammation. This inflammation is implicated in neurocognitive disorders like Alzheimer’s and Parkinson’s. Pine Bark Extract reduces free radical production, boosts neuron’s natural antioxidant defense systems, and is a potent free radical scavenger.

The active polyphenols called proanthocyanidins in Pine Bark Extract easily cross the blood-brain barrier. How does Pine Bark Extract Work in the Brain? Pine Bark Extract boosts brain health and function in several ways. But two in particular stand out. 1. Pine Bark Extract boosts cerebral blood flow. Pine Bark Extract’s main active component are water-soluble polyphenols. Including bioflavonoids catechin and taxifolin as well as phenol carbonic acids. Antioxidants like bioflavonoids enhance blood vessel nitric oxide (NO) synthase expression. Which then releases NO from endothelial cells (blood vessels linings). It’s a little difficult to measure blood flow in the brain. So researchers conducted a double-blind, randomized, placebo-controlled study using Pycnogenol to study forearm blood flow responses to acetylcholine (ACh). The study was with healthy young men before and after 2 weeks of 180 mg per day of Pycnogenol, or a placebo. The group of men using Pycnogenol experienced a significant increase blood flow. The researchers then introduced an NO synthase inhibitor which completely abolished Pycnogenolinduced increases in blood flow. And concluded that it was definitely Pycnogenol that increased blood flow by boosting nitric oxide production in blood vessels.825

2. Pine Bark Extract boosts cognition. Neurohackers report that supplementing with Pine Bark Extract has a significant effect on memory, focus, decision-making and mood. And researchers verified this in a clinical setting. In this study, 60 participants aged 35-55 volunteered to work with researchers. Diet, alcohol, and lifestyle patterns, including exercise, were controlled. Half the group received 50mg of Pycnogenol 3times per day for 12 weeks. The other half simply followed a healthy lifestyle. After 12 weeks of Pycnogenol supplementation, results showed a 16% increase in mood, an 8.9% increase in mental performance, 13.4% increase in sustained attention, and a 30% decrease in oxidative stress. A 13% increase in attention span may not seem like a big deal. But the National Center for Biotechnology Information reported that the average American’s attention span has reduced from 12 seconds to 8 seconds.826 This decrease in attention span can have a profound effect on productivity and quality of work produced. So supplementing with Pine Bark Extract could be the simplest way to dramatically increase your productivity and income. And get that next promotion. How things go bad Poor cerebral blood flow, inflammation, and free radicals (oxidative stress) can damage your brain. And one of the ways this manifests is memory loss. Left unchecked, it can develop into serious neurodegenerative diseases like Alzheimer’s and Parkinson’s Disease. ↓Cognitive function declines ↓Heavy metals kill brain cells from the inside ↓Free radicals destroy neurons and synapses ↑Anxiety, depression and moodiness increase ↓Attention, concentration, and memory declines Poor cerebral circulation causes a domino effect in the brain affecting many critical processes. Memory, cognition, and decision-making all suffer as a result. Pine Bark Extract benefits Pine Bark Extract and Pycnogenol are Oligomeric proanthocyanidins (OPCs). And OPCs have been extensively researched since the 1040’s. Professor Jacques Masquelier published his doctoral thesis in 1948 on OPCs, phytochemistry and human health. Masquelier discovered that OPCs could neutralize free radicals which were identified in a number of degenerative conditions and age-associated changes in the body. He found that OPCs were potent antioxidants.

In 1965, Horphag Research of Germany began research on their patented water-soluble Pine Bark Extract called Pycnogenol. More than 370 clinical studies have since been conducted. Showing Pine Bark Extract benefits for: • • • • • • • • • • • •

Cognitive functions including memory, mood, and ADHD Antioxidant & anti-inflammatory properties Cardiovascular benefits preventing heart disease and stroke Diabetes by controlling blood glucose levels Eye health by improving blood flow to tiny capillaries in the eye Improved sperm quality and erectile dysfunction Menstrual disorders including PMS symptoms Joint health including osteoarthritis, mobility, flexibility, and chronic pain Oral health including gum bleeding and plaque formation Respiratory functions like taming asthma and hay fever Sports nutrition for energy, recovery, cramps, and better blood flow Overall blood vessel health827

Pine Bark Extract and the patented Pycnogenol are powerful, multi-modal defenses against aging, diseases, and overall brain health. How does Pine Bark Extract feel? Pycnogenol and Pine Bark Extract are one of the most potent antioxidants ever discovered. Many neurohackers report having more energy. And an improved attitude while using this supplement. The effects of Pine Bark Extract are often not felt immediately. But seem to build over time. For some, you’ll feel a boost in energy about 6 hours after taking it. Adding Pine Bark Extract to your stack should have you thinking faster and clearer. You may get more done. And stay focused on things longer until you’re able to finish them. But chances are you may not ‘feel’ anything at all. Until later you realize that you feel ‘normal’. And find you’re able to recall words and names much more easily. Over the long-haul you may realize you have more stamina and energy. It simply makes you feel good. Older neurohackers report Pine Bark Extract: • • • • • • • • •

Reduces age spots, varicose veins, and spider veins Hair, skin, and nails look smoother and take on a healthy glow You don’t bruise as easily Allergies and sinus issues clear up Blood sugar levels return to normal after 2-3 months No more hemorrhoids Leg, joint and knee pain are reduced Runners can go longer without feeling exhausted You don’t feel completely burnt out after a workout

•

You may be able to lift more weight and not get as sore

Male neurohackers nearly always report more frequent and harder erections. Especially when stacking with L-Arginine. And a higher sperm count. Which is backed by science.828 Long term users say they consistently feel calmer, can think quicker, and have better memory. Pine Bark Extract Clinical Research Pine Bark Extract boosts Working Memory Australian researchers worked with 101 patients (aged 60 – 85 years) in a double-blind, placebocontrolled study. Participants received 150 mg of Pycnogenol daily for 3 months. The cognitive tasks measured in the study included attention, working memory, episodic memory, and psychomotor performance. The study found statistical evidence that the Pycnogenol-group developed better working memory as a result of using Pycnogenol.829 Pine Bark Extract for Improved Cognition This 12-weeks study was conducted in Italy with 60 professionals aged 35-55 years. Half the group received 150 mg per day of Pycnogenol. And the other half took a placebo. At 12 weeks the improvement in the Pycnogenol-group was more significant than the controls. Free radicals were reduced by 30.4%. The group showed improvement in spatial memory retention. Alertness, anxiety, and contentedness all improved. The researchers concluded that Pycnogenol improved cognitive function, and mental performance.830 Another study in Italy was done with university students. The objective of the study was to test supplementation with Pycnogenol on cognitive function, attention, and mental performance. 53 students (18-27 years) were given Pycnogenol for 8 weeks. Another group of students took a placebo. The study found that the students who used the nootropic experienced better sustained attention, memory, executive function, and mood. The study concluded that Pycnogenol improves cognitive function in normal students.831 Pine Bark Extract for ADHD Several studies have been conducted with Pine Bark Extract and its effects on those with ADHD. One study in the Slovak Republic gave ADHD children either a placebo or Pycnogenol for one month. Research has shown that concentrations of catecholamines (dopamine and norepinephrine (NA)) were higher in urine of ADHD patients compared to healthy children. Higher concentrations of NA correlated with degree of hyperactivity. And both adrenaline and NA concentrations correlated with higher blood levels of oxidized glutathione (GSSH). Treatment of Pycnogenol with ADHD children decreased dopamine and NA urine concentrations. And

increased the GSH/GSSG ratio. Leading to less hyperactivity. And reduced oxidative stress.832 Another study in Slovakia was conducted with 61 ADHD children. The kids were given 1mg/kg/day of Pycnogenol for 4 weeks in this randomized, placebo-controlled trial. The children were examined at the beginning of the trail. And tested again one month later. Results of the study showed those who used Pycnogenol had a significant reduction in hyperactivity, improved attention and visual/motor skills, and better concentration. The study concluded that Pycnogenol could be used as a natural supplement to relieve ADHD symptoms in children.833 Pine Bark Extract Recommended Dosage Recommended dosage of Pine Bark Extract containing 95% proanthocyanidins is up to 100 mg 3-times per day. Or 1.4 mg per pound of body weight. So if you’re 200 pounds, your daily dose would be 280 mg. Higher dosing should be divided equally with your first dose in the morning, next dose at noon and a dose mid-afternoon. Pine Bark Extract is water-soluble so can be taken with water or mixed in a smoothie. Pine Bark Extract Side Effects Side effects for Pine Bark Extract and Pycnogenol are rare when taken in doses from 50 – 450 mg daily. Very rarely will you experience dizziness, stomach problems, headache, or mouth ulcers. Pycnogenol can boost your immune system. So if you’re on medication for auto-immune diseases like multiple sclerosis (MS), lupus, rheumatoid arthritis, and others. Or taking an immune suppressant for an organ transplant. You should avoid using Pine Bark Extract or Pycnogenol. High doses of Pycnogenol may increase bleeding if you are dealing with a bleeding condition. Very high doses of Pycnogenol may decrease blood sugar too much if you’re dealing with diabetes. Pycnogenol may slow blood clotting. So stop using this nootropic if you’re planning on having surgery or dental work. Type of Pine Bark Extract to Buy The bioactive component of Pine Bark Extract are proanthocyanidins. Pycnogenol is standardized to 65-75% proanthocyanidins. Regular Pine Bark Extract is often standardized to 95% proanthocyanidins. Pine Bark Extract supplements are available as a powder, capsules, and tablets. Check the label for the concentration of proanthocyanidins. Nootropics Expert® Recommendation Pine Bark Extract (Pycnogenol) 300 - 400 mg per day

I recommend using Pine Bark Extract or Pycnogenol® as a nootropic supplement. Your body does not make Pine Bark Extract on its own. So you must take it as a supplement. Pine Bark Extract easily crosses the blood-brain barrier and is available within an hour of taking it. Effects are more typically felt within 6 hours of taking it. Pine Bark Extract is especially helpful for those suffering from brain fog or memory loss. It helps increase cerebral blood flow and bringing more oxygen and nutrients to brain cells. Pine Bark Extract is helpful for those dealing with ADHD. Research shows the extract helps modulate dopamine and norepinephrine in your brain. Which is a common problem with those dealing with ADHD. Taken for ADHD symptoms, Pine Bark Extract helps reduce hyperactivity, improves focus and attention, improves memory, and puts you in a better mood. Pine Bark Extract is also helpful for those suffering from Alzheimer’s. It has been shown to boost blood flow to areas of the brain affected by amyloid-β protein aggregation. And even may prevent the proteins from forming. Pine Bark Extract helps tame inflammation associated with diseases like Alzheimer’s. And studies are now underway to determine if Pine Bark Extract can help prevent Alzheimer’s from taking hold in the first place. You can safely take up to 450 mg of Pine Bark Extract (95% proanthocyanidins) daily if needed. Half the dose first thing in the morning. And the other half at noon. And your final dose mid-afternoon. And for memory, Pine Bark Extract is great to stack with most of the racetams. Neurohackers also report good success stacking the extract with Bacopa Monnieri, Lion’s Mane, and Rhodiola Rosea.

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Piperine Piperine has been shown to amplify the effects of nootropics, decrease anxiety, improve mood and boost memory Piperine is an alkaloid extracted from Black Pepper (Piper Nigrum). And used to increase the bioavailability and metabolism of nootropic supplements and drugs. Black Pepper (Piper Nigrum) is a flowering vine native to south India. Its dried fruit is used world-wide as a spice and seasoning. Piperine was discovered in 1819 by Hans Christian Ørsted who isolated it from Piper Nigrum. This is the same Danish chemist who figured out that electric currents create magnetic fields.834 Piperine’s effects are similar to grapefruit juice and St. John’s wort. Piperine makes nootropics and pharmaceuticals more bioavailable by inhibiting the drug transporter P-glycoprotein and inhibiting the major drug-metabolizing enzyme CYP3A4 primarily in your liver.835 This action amplifies the effect of nootropics by preventing elimination in your liver and urine. And allowing increased absorption for use by your body and brain. But Piperine does more than just boost the action of your nootropic stack. It acts as a nootropic as well. In this chapter we investigate how Piperine can help optimize your brain. Research has found Piperine can protect against oxidative damage by inhibiting free radicals and reactive oxygen species. Piperine protects against oxidative stress. And has been found to have antimutagenic and anti-tumor capabilities.836 How does Piperine work in the Brain? Piperine boosts brain health and function in several ways. But two in particular stand out. 1. Piperine is an anti-depressant. Piperine is a monoamine oxidase (MAO) inhibitor (MAOI). Piperine inhibits both MAO-A and MAO-B. Research has found that Piperine is as effective as the popular pharmaceutical antidepressant Prozac® (fluoxetine).837 Piperine has a profound effect on serotonin in the brain. Piperine has been shown in the lab to provide a substantial increase in serotonin (5-HT) in both the hippocampus and frontal cortex.838 And this is where it gets very interesting. Scientists found that combining Piperine with Resveratrol provided significant antidepressant action. But this stack also offered relief from oxidative stress, inflammation and provided neuroprotection.839 Resveratrol on its own is a good antidepressant. And Piperine also provides antidepressant action as a MAO Inhibitor and serotonin booster. When combined, Piperine also boosts the bioavailability of Resveratrol. This combination is a potent natural antidepressant. Without the side effects that come with prescription MAOI’s and SSRI’s.

2. Piperine boosts bioavailability. Piperine inhibits the drug transporter P-glycoprotein, and the major drug-metabolizing enzyme CYP3A4. This can have profound implications on how well and how much of each nootropic in your stack actually gets to your brain. Your liver protects you by attaching a glucuronide molecule to nootropics (and drugs) which sends a signal for them to be excreted in your urine. This process prevents excessive levels of nootropic supplements (and drugs) in your body. But it can also work against your brain optimization goals. A great example is curcumin, the bioactive compound found in turmeric. You will not experience the medicinal properties of curcumin when taken on its own. Curcumin has very poor bioavailability when taken as a supplement because of its rapid metabolism in your liver and intestinal wall. Researchers in India gave mice 2 grams/kilogram of curcumin and tested blood levels over 4 hours. Very small amounts of curcumin were detected in blood in the first 2 hours. The scientists then administered the same amount of curcumin combined with 20 mg/k of Piperine. Blood levels of curcumin were detected sooner with Piperine added. And stayed in the blood longer. Bioavailability of curcumin in mice increased by 154% when combined with Piperine. The researchers then tried the experiment with humans. A 2-gram dose of curcumin on its own was not detectable in blood samples. But curcumin combined with Piperine in humans made a profound difference. 2-grams of curcumin combined with 20 mg of Piperine in humans showed up in blood samples within 15 minutes. And Piperine increased the bioavailability of curcumin by 2000%.840 How things go bad The job of our liver is to clear our body of unwanted compounds and toxins. And excrete them as waste through our urine. But some of the nootropics and especially prescription drugs are seen as “foreign matter” by our liver. The nootropics are eliminated as ‘waste’ even if our intention was to benefit our body and brain. To make matters even worse, add aging to the mix. And then our brain chemistry and energy metabolism changes. ↓ Serotonin, dopamine and norepinephrine levels decline ↓ Recall, reaction time and mood diminish ↓ Toxins, oxidation and free radicals damage neurons ↓ Brain cell membranes degenerate ↓ Bioavailability of nootropics and supplements decline All of these changes can happen at any age. And some are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia.

This is where Piperine can help. Piperine benefits Research from hundreds of studies have shown that Piperine will: • • • • • • •

Boost the bioavailability of nootropics Increase the effectiveness of nootropics Work as an antidepressant Relieve oxidative stress Prevent inflammation Provide neuroprotection Protect against tumors and cancers

How does Piperine feel? Piperine on its own has antidepressant capabilities. So you may feel your mood improve. If you are using curcumin or turmeric for its anti-inflammatory benefit, you’ll likely find that these supplements will be much more effective in relieving pain by adding Piperine. You should notice a substantial benefit in the effectiveness of most nootropics and prescriptions meds when stacked with Piperine. Some neurohackers report a reduction in anxiety (that can be caused by some supplements) by taking it with Piperine. If you are dealing with arthritis, you may find pain levels will decrease by using Piperine. This nootropic is a potent anti-inflammatory even on its own. You may be able to reduce the amount of some nootropics and medications by stacking them with Piperine. Because the effectiveness of most of these supplements and meds will get a boost by combining them with Piperine. The Research Piperine Potentiates the Effects of Curcumin Stress in everyday life puts every one of us in danger of developing some type of cognitive disorder. And curcumin is a proven therapy to help protect us from this assault on our cognition and brain health. To help illustrate what happens in our brain when under stress, scientists subjected male Laca mice to stress-induced cognitive impairment for 28 days. Chronic stress impaired memory, locomotor activity, elevated toxins like nitrate, decreased the master antioxidant glutathione, damaged mitochondria enzyme function, reduced acetylcholine levels, and increased stress cortisol levels. Researchers then treated the mice with either 200 or 400 mg/k per day of curcumin. All of the damage

caused by stress was reversed to a certain extent. Then the team added 20 mg/k of Piperine to a reduced daily curcumin (100 or 200 mg/k) supplement. The results clearly demonstrated that Piperine enhanced the bioavailability of the curcumin. And greatly potentiated the effects against stress-induced cognitive impairment.841 Piperine as an Antidepressant Researchers injected mice with 60 mg/k of Piperine. An hour after the injection, the team measured serotonin, dopamine and norepinephrine levels. Serotonin levels were significantly higher in the cerebral cortex of the mice. Dopamine levels were markedly higher in the hippocampus, midbrain and cerebellum. And norepinephrine levels were lower in every part of the brain.842 Scientists in Korea analyzed Piperine (ethanol extract) for its monoamine oxidase (MAO) inhibitor capabilities. Piperine showed an inhibitory effect against MAO-A and MAO-B. The team found that Piperine exhibited the same type of antidepressant effect in the brain as the popular prescription drug Prozac® (fluoxetine). The researchers concluded that Piperine possesses potent anti-depressant properties. And Piperine is a promising pharmacotherapeutic candidate as an antidepressant agent.843 Piperine Protects Against Alzheimer’s A study conducted in Thailand looked at Piperine’s effect on memory and neurodegeneration in an animal model of Alzheimer’s Disease. Adult male Wistar rats were given Piperine at doses ranging from 5, 10 and 20 mg/k of body weight for 2 weeks before and 1 week after artificially induced Alzheimer’s-like conditions in the rat’s brain. The results showed that Piperine at all dosage ranges significantly improved memory impairment and neurodegeneration in the hippocampus. The scientists speculated the mechanism of action for Piperine to produce these effects could be a decrease in lipid peroxidation and the acetylcholinesterase enzyme. (This enzyme degrades acetylcholine synthesis in the brain). Piperine also demonstrated a neurotrophic effect in the hippocampus.844 Dosage Notes The recommended dosage of Piperine to enhance bioavailability of nootropic supplements is 5 - 20 mg per day. Many nootropic stacks and some supplement formulas (i.e. curcumin, turmeric and resveratrol) come pre-stacked with the appropriate dose of Piperine. Side Effects Piperine is an extract of Black Pepper and considered non-toxic and safe to use at recommended doses.

Piperine potentiates the effect of nearly all nootropic supplements and prescription medications. So be very aware that boosting the effects of certain supplements or drugs could produce unwanted consequences. Be cautious of using Piperine in addition to Piperine that may already be in one or more of your supplements. Too much Piperine will not only amplify most of the supplements and drugs you’re taking. But could also negate the effects of some. Available Forms BioPerine® is a patented form of Piperine made by Sabinsa Corporation. And licensed to other supplement manufacturers to include in their formulas, or as a standalone product. It’s the only source I’m aware of who have clinical studies to back up their claims of safety and efficacy. You can also get Piperine by grinding black peppercorns on your food. The problem is there is no way to measure how much Piperine you’re actually using. Nootropics Expert® Recommendation Piperine up to 20 mg per day I recommend using Piperine as a nootropic supplement. Your body does not make Piperine on its own. So you must take it as a supplement. Piperine is especially helpful for boosting the bioavailability of other nootropics in your stack. Beware that Piperine also amplifies the potency of other supplements and meds you are taking. Boosting the effect of certain SSRI’s and some other meds could be extremely dangerous. Piperine is also an effective antidepressant, and can help lower stress and anxiety. Piperine is a potent anti-inflammatory and could help reduce pain if you are dealing with arthritis. Or other conditions caused by excess inflammation in your body. Piperine is a powerful neuroprotectant and makes a great addition to any nootropic stack.

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Piracetam Piracetam has been shown to increase cerebral circulation, improve creativity and verbal fluency, boost memory, learning and recall and improve mood Piracetam (2-oxo-1-pyrrolidine-acetamide, Nootropil) was the first in the racetam-family of nootropic compounds. It is a water-soluble ampakine nootropic. AMPA (α-amino-3-hydroxy-5-methyl-4isoxazolepropionic) refers to one of three glutamate receptors in your brain.845 Developed by a fellow of famous Russian physiologist Ivan Pavlov, Dr. Corneliu Giurgea first synthesized Piracetam at Belgian-based pharmaceutical company UCB Pharma in the 1964. Piracetam is considered the first true nootropic ever developed. As a cyclic derivative of GABA, Piracetam was first intended to be a calming type of drug for motion sickness. But in spite of its connection with GABA, Piracetam didn’t show the behavior usually associated with this calming neurotransmitter. And cannot directly affect GABA receptors.846 Instead, Dr. Giurgea discovered that Piracetam was able to boost cognition even in healthy people. The company launched this new ‘drug’ as ‘Nootropil’ in Europe in the early 1970’s. The success of Nootropil soon allowed UCB Pharma to expand its operations which led to many new pharmaceutical drugs. Dr. Giurgea coined the term “nootropic” to describe this class of cognition-optimizing compounds.847 Nootropic was derived from the Greek words for “mind” (noos) and “towards” (trepein). Piracetam is sold as a prescription drug (Nootropil and Lucetam) in Europe. In South America, Piracetam is sold under the names Noostan (Argentina), Breinox (Venezuela and Ecuador), and Nootropil (Mexico). Piracetam is also branded as Lucetam, Oikamid, Smart, Geratam, Biotropil, Neurobasal, Stimulan and Nocetan in countries around the world. In the United States, Piracetam is sold as an OTC supplement as Piracetam and Nootropil. Dozens of racetam derivatives have since been developed based on the original Piracetam. All synthetic compounds, racetams share a pyrrolidone nucleus. Piracetam is a cyclic derivative of GABA. But oddly enough, it doesn’t affect GABA receptors in the brain. Instead, Piracetam was found to modulate AMPA and NMDA receptors and improve the function of the neurotransmitter acetylcholine (ACh). AMPA and NMDA receptors along with acetylcholine are associated with learning and memory.848 And when Piracetam is stacked with a choline supplement its effects are even more pronounced. Researchers have shown in hundreds of clinical studies that Piracetam significantly improves learning and memory. Piracetam also increases cerebral blood flow. Blood delivers oxygen and glucose needed for cellular metabolism and helps carry away cellular waste. Critical for the highly optimized brain. If you’re going to start experimenting with racetams, my recommendation is to start with Piracetam.

Because it works, it’s safe and it’s cheaper than all the other nootropics in the racetam-family. Piracetam helps: •

• •

Inflammation: Piracetam is a potent analgesic (anti-pain). This analgesic effect is related to inhibition of inflammatory markers including IL-1β. And the prevention of reduced glutathione, ferric reducing ability and free radical scavenging ability.849 Neurotransmitters: Piracetam potentiates the flow of and increases the effect of acetylcholine (ACh) in the brain.850 And studies have shown it significantly improves learning and memory.851 Cerebral Blood Flow: Piracetam increases blood flow in the brain.852 Better blood flow delivers more oxygen and nutrients to neurons improving cognition, memory and focus.

How does Piracetam work in the Brain? Piracetam boosts brain health and function in several ways. But two in particular stand out. 1. Piracetam modulates AMPA and NMDA receptors in the brain. And improves the flow of acetylcholine (ACh) and sensitivity and density of ACh receptors.853 This German study conducted with lab mice showed Piracetam elevated NMDA receptor density. And normalized the way those receptors worked with L-Glutamate similar to that of a healthy brain. Deficits at the level of NMDA receptors could be one of the mechanisms of action underlying agerelated cognitive decline. And the researchers concluded that Piracetam showed cognition-enhancing properties.854 This effect on NMDA receptor sites is directly related to our interest in using Piracetam for Long-Term Potentiation and the support of long-term memory formation. Neuroplasticity is dependent on activation of NMDA receptors.855 And this neuroplasticity is at the heart of memory formation. Reviews of Piracetam used by neurohackers frequently report the return of longlost memories. Further proof of the efficacy in using Piracetam to support learning and memory. 2. Piracetam increases cerebral blood flow. Several studies have shown how Piracetam positively influences brain blood flow. Cerebral blood flow is critical for the highly optimized brain. Blood delivers oxygen and glucose needed for cellular metabolism and helps carry away cellular waste.856 Strokes can be caused by an interruption in cerebral blood flow. Starving parts of the brain of oxygen and glucose. This double-blind, placebo-controlled study was done with 24 stroke patients. One group received 2,400 mg of Piracetam twice daily, and the other a placebo. Before treatment, both groups were comparable in performance during language tasks. The study found that Piracetam improved recovery of various language functions. And this effect was attributed to increased blood circulation to areas of the brain related to language. The placebo group showed very little improvement in areas of language.857

How things go bad As we get older, our brain chemistry and metabolism changes. And it seems these changes are affecting younger and younger people. ↓ Recall, reaction time and learning capacity declines ↓ ATP energy levels decline ↓ Density of AMPA and NMDA receptors decline ↓ Acetylcholine levels decline ↓ Cerebral blood flow declines All of these changes are contributing factors to age-related cognitive decline. Early signs of these effects can be seen in poor decision-making, difficulty learning, and even recalling simple things like an important appointment. But even if you’re not concerned with the signs of aging, Piracetam can help. Piracetam benefits Piracetam helps increase blood flow in the brain, improves oxygen levels, enhances glucose use in brain cells, maintains brain cell mitochondria and ATP synthesis. Piracetam is also a potent modulator of AMPA-sensitive glutamate receptors in neurons. It increases the density of specific binding sites for AMPA in neuronal synapses.858 Glutamate is the primary excitatory neurotransmitter in your brain. This glutamate activity by Piracetam affects alertness, focus, attention, memory and learning. And one of the reasons why neurohackers consistently report that Piracetam improves mental performance and memory. Piracetam increases high-affinity choline uptake (HACU) which is the process that occurs in cholinergic nerve endings and facilitates acetylcholine (ACh) formation. Boosting ACh with Piracetam produces a powerful effect on learning and memory.859 Piracetam also boosts choline receptor density in the frontal cortex. The area of your brain used for working memory and decision-making.860 ATP energy is critical to your brain’s survival. Brain cells must produce all of their own ATP from glucose and oxygen. This brain energy carbohydrate metabolism depends on cerebral blood flow, oxygen uptake and glucose. Piracetam enhances this glucose utilization and increases ATP synthesis within brain cell mitochondria.861 And Piracetam has analgesic (anti-pain) benefits. This anti-pain action is linked to Piracetam’s antiinflammatory properties.862 Inflammation can cause pain, and studies have shown Piracetam can have profound effect on pain.

Piracetam boosts acetylcholine so you should add a good choline source. Try Alpha GPC or CDPCholine with Piracetam. And give your brain the choline it needs. How does Piracetam feel? Most neurohackers report a noticeable benefit from Piracetam after about 2 weeks. Consider that Piracetam is modulating your brain’s chemistry. And this change is unlikely to occur immediately. Your brain needs some time to adjust to the new change in acetylcholine (ACh) levels and how it uses it. Increased cerebral blood flow takes a while to bring up levels of oxygen and nutrients. And for your neuronal cells to respond. Your mileage may vary depending on your own neuro-chemical makeup. Many suggest starting with an ‘attack dose’ for the first 3-days. A 3,000 mg ‘attack dose’ of Piracetam for example to start with theoretically gets more of the supplement into your system right away. So it takes less time to build up before you start feeling the effects. From there, step down to a maintenance dose and vary the quantity until you find your own sweet spot. Once you begin to notice the effects of Piracetam you’re likely to feel a mood boost, less social anxiety, heightened creativity, improved verbal fluency and better memory. Piracetam does boost your brain’s use of acetylcholine. So you will likely find that adding a good choline source (Alpha GPC or CDP-Choline) to your Piracetam stack helps improve the effectiveness of this nootropic. And help avoid a ‘racetam-headache’. The Research We have plenty of evidence that Piracetam improves memory in animals and people who are suffering from many types of cognitive impairment. Keep in mind that most of the scientific research available for nootropics is done for sick people trying to get well. The return on investment for research at institutions and universities comes from treating diseases. And not from helping ordinary biohackers like us trying to get a competitive advantage at work or in school. We can however extrapolate the findings from these studies and learn if and how something like Piracetam can help our memory and cognition. Once-in-awhile someone does take the time to conduct such a study on healthy people. Like this one done with normal, healthy volunteers. Researchers gave this healthy group of participants four 400 mg capsules of Piracetam 3-times per day (4,800 mg total) for 14 days. No effects on memory were observed after 7 days during this experiment. But after 14 days verbal learning had significantly increased.863 Piracetam Improves Cognition Researchers in Belgium (where Piracetam originated) conducted an analysis of 19 double-blind, placebo-controlled studies done with patients suffering dementia or cognitive impairment and who took Piracetam. The results of this meta-analysis demonstrated the difference between people who used Piracetam or

used a placebo. The end result of this analysis provided compelling evidence for the usefulness of Piracetam in a diverse group of people with cognitive impairment.864 Several studies and user reviews have shown that Piracetam dosage makes a difference. And unlike some other nootropics where you start at a lower dose and work your way up, with Piracetam I recommend you start at a higher dose. This study in Germany with 78 elderly patients showed that there was a significant difference in cognition improvement while dosing Piracetam at 1,600 mg 3-times per day (4,800 mg total). There was no difference in cognition with patients who received 800 mg 3-times per day.865 Piracetam Enhances ATP Production Piracetam is used around the world to treat cognitive impairment in aging, brain injuries, dementia and Alzheimer’s Disease. Several studies show that Piracetam enhances ATP production, mitochondrial membranes, and neurite outgrowth in neurons. In this study, scientists investigated the effects of Piracetam on mitochondrial function. Human brain cells were treated with Piracetam under normal conditions and under conditions imitating aging and damage by ROS (reactive oxygen species). And with cells representing early-stage Alzheimer’s Disease. The cells representing Alzheimer’s conditions showed impaired mitochondrial function under baseline conditions. Piracetam was able to restore this impairment in cells and shift mitochondrial function back to normal. The researchers showed that Piracetam is able to repair mitochondria in those with mild Alzheimer’s and return cell function back to normal.866 Dosage Notes Recommended Piracetam dosage is 1,600 mg 3-times per day. One Piracetam dose in the morning, and one in the early afternoon, and one later in the afternoon. You will likely want to start with an ‘attack dose’ when you’re first starting out with Piracetam. Refer to the “How does Piracetam feel?” section of this chapter for more on ‘attack doses’. Dosing Piracetam varies widely between neurohackers. Experimenting and finding the dose where you experience the most benefit is key. You may find a lower dose works well for you. Or you may find you need to increase your dose even more. Dosing Piracetam is directly related to your own unique neurochemistry. Side Effects Piracetam is non-toxic. So is considered well-tolerated and safe. As with many of the racetams, Piracetam can cause headaches because it boosts the use of acetylcholine in your brain. Choline supplements like Alpha GPC or CDP-Choline can help you avoid this side effect.

Many neurohackers find that stacking Piracetam with a choline supplement boosts the effect with improved memory and cognition. And this is supported in several research studies.867 Available Forms Piracetam is sold in tablet, capsule and powder form. Tablets and capsules are usually 800 mg each. In Europe, Asia, South America, and some other countries around the world, Piracetam is a prescription drug. And sold under many different brand names (including Nootropil). Refer to the Introduction of this chapter for some of these brand names. Nootropics Expert® Recommendation Piracetam 1,600 mg 3-times per day I recommend using Piracetam as a nootropic supplement. Your body does not make Piracetam on its own. So to get its benefits you must take it as a supplement. If you’re going to start experimenting with racetams, my recommendation is to start with Piracetam. Because it works, it’s safe and it’s cheaper than all the other nootropics in the racetam-family. Piracetam is especially helpful for those suffering from most types of age-related cognitive decline. Piracetam is also particularly useful to students and executives who want to boost cognition, learning and memory. You should use Piracetam with a good choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain. You can safely boost daily intake of Piracetam to 9,600 mg if needed. Studies have shown that Piracetam is completely non-toxic even at high doses. You may find however that a lower dose than my recommended amount works better for you.

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Polygala Tenuifolia Polygala Tenuifolia is known for its anti-anxiety and stress-relieving effects, reducing depression, and promoting restful sleep Polygala Tenuifolia (Yuan Zhi, Polygala Tenuifolia) is an herb belonging to the Milkwort family. It’s root -known as Polygalae Radix has been used for over 2000 years in Traditional Chinese Medicine. The active components found in Polygala Tenuifolia include saponins, ginsenosides, oligosaccharides, ketones, alkaloids, polysaccharides, and flavonoids.868 In Chinese, it is called “Yuan Zhi” and has traditionally been used for memory and to prevent Alzheimer’s and dementia. In Korean traditional medicine, it is used as an anti-psychotic because it is a serotonin and dopamine receptor antagonist869 Polygala Tenuifolia is officially listed in the Chinese Pharmacopoeia Commission, 2015. The rhizome of Polygala Tenuifolia is used in making cough medicine and for respiratory disorders because it helps clear air passages.870 Polygala Tenuifolia has also been used traditionally to reduce inflammation, learning and memory, dementia, anxiety, energy, and cancer.871 In 2014, a study conducted at the Peking Union Medical College in Beijing found Polygala Tenuifolia extract worked as an acetylcholinesterase inhibitor (AChE) which increases acetylcholine activity in the brain. The researchers also found Polygala Tenuifolia extract acted as a monoamine oxidase inhibitor (MAOI) which increases dopamine and norepinephrine use in the brain. Inhibiting both of these enzymes resulted in improved learning and memory.872 How does Polygala Tenuifolia work in the Brain? Polygala Tenuifolia boosts brain health and function in several ways. But two in particular stand out. 1. Polygala Tenuifolia for learning and memory. Studies show Polygala Tenuifolia supports dopamine and norepinephrine signaling, upregulates acetylcholine and brain-derived neurotrophic factor (BDNF), and boosts synaptic transmission in the hippocampus for better learning and memory.873 A study conducted at Seoul National University wanted to find out if Polygala Tenuifolia extract (BT11) could enhance memory in healthy humans. Participants received capsules of BT-11 or a placebo 3-times per day for 4 weeks. The study found those supplementing with BT-11 showed significant increases in working memory but not the placebo group.874

2. Polygala Tenuifolia for depression. In animal studies, the compound 3,6′-disinapoyl sucrose (DISS) found in Polygala Tenuifolia has been shown to inhibit both MAO-A and MAO-B, reduces cortisol release, and superoxide dismutase (SOD) activity (which causes oxidative stress). The reduction of cortisol, oxidative stress, and increased dopamine and norepinephrine release acts has consistently been shown to act as an anti-depressant.875 How things go bad Neurotransmitter dysfunction, oxidative stress, increased cortisol, and inflammation often results in: ↑ Increased depression ↓ Memory loss ↑ Insomnia ↑ Obesity ↑ Anxiety Supplementing with Polygala Tenuifolia has been shown in multiple clinical studies as well as user reports to relieve anxiety and depression, improve memory, support healthy sleep, and avoid neurodegenerative disease. Polygala Tenuifolia benefits Polygala Tenuifolia is one of the most frequently mentioned herbs in the Zhong Hua Yi Dian (“Encyclopedia of Traditional Chinese Medicine”) for memory disorders and improvement.876 Polygala Tenuifolia acts as an MOA inhibitor which increases dopamine and norepinephrine in your brain. This ancient Chinese herb helps reduce cortisol, inhibits inflammation, and regulates glutamate AMPA receptors. Polygala Tenuifolia extract has been shown to reduce the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-8 levels in the hippocampus. Which has been shown in animal studies to have a significant effects on learning and memory. Polygala Tenuifolia boosts the expression of brain-derived neurotrophic factor (BDNF) and Nerve Growth Factor (NGF), increase synaptic plasticity, and decrease the accumulation of amyloid β-protein implicated in Alzheimer’s Disease. It has also been found to increase dopamine neurons and improve motor impairment in Parkinson’s Disease.877 Neurohackers consistently report Polygala Tenuifolia is a potent anxiolytic and reduces anxiety quickly especially when used sublingually.

How does Polygala Tenuifolia feel? Neurohackers report feeling calmer and more focused the first day they used Polygala Tenuifolia. For some it can take a week or two to feel the full benefit of this supplement. Some say it provides a nice but small mood boost and they prefer it over St. John’s wort. Polygala Tenuifolia seems to be effective for Seasonal Affective Mood Disorder (SAD). The calming benefit of Polygala Tenuifolia is more pronounced and happens quicker when used sublingually. “Within less than a minute it felt like the Divine hand came down and grabbed all the negativity and replaced it with serenity and a strong not giving a f**k feeling”. Used sublingually, some say using Polygala Tenuifolia was more effective for sleep than any other nootropic they’ve tried. Polygala Tenuifolia is a game-changer for some because it gives them the mental space to become the observer and be more mindful. Making it easier to recognize and mitigate negative thought patterns. Like any nootropic supplement, Polygala Tenuifolia will not work for everyone. But if you are fortunate and it works for you, it may help you feel again, music may sound better, and you’ll feel human again. Polygala Tenuifolia Clinical Research Most of the clinical studies with Polygala Tenuifolia are animal studies. The very few with humans have been conducted with the elderly for improving working memory and cognition. And for improving sleep. Polygala Tenuifolia for sleep The active component found in Polygala Tenuifolia that provides it sedative effective is Senegenin.878 A study conducted in China using mice found the Tenuifolin found in Polygala Tenuifolia increased non-rapid eye movement (NREM) and rapid eye movement (REM). Mimicking natural sleep patterns. The researchers found the sleep-enhancing effects of this herbal extract were due to decreased norepinephrine, and increased GABA and acetylcholine levels in brain regions involved with sleep.879 Polygala Tenuifolia improves memory Polygala Tenuifolia has been used for centuries as a sedative. And more recent research shown its effectiveness for improving memory in animal studies and in healthy humans. So, researchers in South Korea wanted to find out if Polygala Tenuifolia extract could also benefit memory in elderly humans. A double-blind, placebo-controlled trial using the extract BT-11 was conducted with approx. 50 elderly

people. The researchers found that supplementing with Polygala Tenuifolia extract (BT-11) significantly improved short-term memory and recall in elderly people. And the research team concluded “BT-11 could enhance some cognitive functions including memory in elderly humans. And may be used as a nutraceutical for disease prevention and/or treatment”.880 Polygala Tenuifolia Recommended Dosage The recommended adult dosage for Polygala Tenuifolia extract is 100 – 300 mg up to 3-times per day. Supplementing with Polygala Tenuifolia at the adult dose has also been found to be safe in children and young people up to 19 years of age.881 Polygala Tenuifolia Side Effects Polygala Tenuifolia is considered non-toxic and safe to use a nootropic supplement. Polygala Tenuifolia may cause vomiting, diarrhea, and mild indigestion in some people. Type of Polygala Tenuifolia to Buy Polygala Tenuifolia extract is available in capsules, tubs of powder, and as a tincture for sublingual use. Users consistently report they experience the benefits of Polygala Tenuifolia faster and it’s more powerful when used sublingually. Nootropic Expert® Recommendation Polygala Tenuifolia extract 100 – 300 mg up to 3-times per day. I recommend using Polygala Tenuifolia extract as a nootropic supplement. Your body does not make Polygala Tenuifolia on its own. So, to get its benefits you must take it as a supplement. Polygala Tenuifolia is especially helpful for those dealing with anxiety and stress. Polygala Tenuifolia is reported to work well for those suffering from insomnia. This Ayurvedic herb helps relieve the symptoms of depression by acting as an MAOI and acetylcholine levels. And reducing the proinflammatory cytokines often found elevated in those with depression. And Polygala Tenuifolia has been found to help with learning and memory particularly with older neurohackers. Polygala Tenuifolia extract is water soluble so can be taken at any time with a glass of water.882 Many report you will feel the benefits of using Polygala Tenuifolia if you take it sublingually.

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PQQ PQQ helps create new mitochondria in brain cells, is a very potent antioxidant, stimulates Nerve Growth Factor, and boosts energy, cognition, memory and learning PQQ (pyrroloquinoline quinone or methoxatin) is a very potent antioxidant and plays a significant role in cognition and memory. PQQ is the first nutrient discovered that promotes the growth of new mitochondria (mitochondriogenesis) in your cells. Brain cells have a higher concentration of these little cellular power plants than most other cells in your body.883 You can have anywhere from two to several thousand mitochondria in each brain cell. They even have their own DNA. When you increase the number of mitochondria, you have more cellular energy to power through your day. PQQ was only discovered recently. But it’s been around for a very long time. So don’t roll your eyes when some New Ager claims that we’re made of stardust. PQQ was discovered aboard NASA’s spaceship “STARDUST” in interstellar dust particles.884 PQQ was first recognized as an enzyme cofactor in bacteria by Norwegian biochemist Jens Hauge in 1964.885 It wasn’t until 2003 that Japanese brain researcher Tadafumi Kato found that PQQ also occurs in rodents and other mammals, including humans. As an enzyme cofactor, PQQ is critical to the life of your brain cells. And some would say it’s even critical to life itself. “Cofactors” are molecules that act as a helper for enzymes that need assistance to work properly. Recent studies verify the unique ability of PQQ to stimulate the creation of new mitochondria.886 And to improve the function of your existing mitochondria. But why would you want to hack your mitochondria? It is an understatement to overstate the dramatic impact this has not only in your brain. But in your entire body. Mitochondria’s role is to convert the food we eat into energy that powers cells to perform at peak function. This process of mitochondriogenesis stops and reverses brain cell death, and brain degeneration. PQQ is the only nutrient that can do this. And more energy in your brain cells means quicker thinking, better memory, amped-up alertness, less mental fatigue and more. PQQ stimulates the growth of new neurons through the promotion of nerve growth factor (NGF) in brain cells. Resulting in improved memory, cognition and learning.887 PQQ is also a potent antioxidant mopping up free radicals that would otherwise damage brain cells. PQQ is used in every cell in your body. And is particularly useful in brain cells. It’s about a close you can get to a vitamin without ‘officially’ being declared a vitamin.

You get PQQ from some of the food you eat including beans, celery, cocoa, fermented foods (i.e. tempeh, natto), kiwi, papaya, parsley, potatoes, spinach and wine. Babies get it from breast milk. How does PQQ work in the brain? PQQ boosts brain health in several ways. But two in particular stand out. 1. PQQ promotes the growth of new mitochondria. This is the only known nutrient that can perform this function. Mitochondria are the source of life and death for neurons. They generate your neuron’s energy and control its death. But mitochondria tend to develop defects as we age. As these defects accumulate, mitochondria start to malfunction. This results in a reduction in cellular energy production. And cells die. The result of this dysfunction can be brain fog, cognition problems, poor memory and recall. And ultimately neurodegenerative diseases like Alzheimer’s, Parkinson’s, Huntington’s, stroke, and others. Studies show that PQQ protects against this cellular damage by repairing and helping to create new mitochondria. Studies with mice and rats and eliminating PQQ from their diet have shown reduced mitochondria. To demonstrate how this process works, scientists added PQQ to mouse cells in the lab. And they showed that PQQ activated the cAMP response element-binding protein (CREB), and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha). This pathway is known to regulate mitochondrial biogenesis.888 2. PQQ helps grow new neurons. This unique nutrient promotes the production of nerve growth factor (NGF). Assisting in brain cell repair, maintenance, and regeneration. Including many of the cells that are crucial for cognition, memory and learning. NGF is especially important for maintaining neuroplasticity. This process is how brain cells form connections to communicate with each other. And is how we learn new stuff and then record it to memory. By stimulating the production of NGF, PQQ has been found to protect memory and cognition in both animals and humans. In one study, scientists demonstrated PQQ’s ability to promote the healing of injured nerves. The team used 90 healthy White Wistar rats and divided them into 3 groups. The rats had injured (purposely) sciatic nerves. And were treated with Vitamin E, PQQ or combination of both. The scientists found that 12 weeks after surgery and the introduction of PQQ to the wound, the nerves grew back! They concluded that the combination of Vitamin E with PQQ promoted nerve regeneration.889 Another way that PQQ influences new neuron development is by protecting neuron stem and progenitor

cells from glutamate toxicity (oxidative damage). This allows neurons to survive and potentially form new brain cells.890 How things go bad As we get older, the chemistry in our brain cells and energy metabolism changes. ↓ Neurons degenerate ↓ Recall, reaction time, memory, and mood diminish ↓ Neurotransmitter levels decline All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. But even if things haven’t degenerated to such a debilitating level, PQQ can help. PQQ benefits Research from hundreds of studies have shown that PQQ will: • • • • • • • •

Boost energy levels and stamina Reduce fatigue Improve sleep Reduce the possibility of age-related diseases Improve cognition, memory, learning and recall Repair damage caused by strokes Protects against Alzheimer’s and Parkinson’s Lowers LDL (bad) cholesterol891

PQQ is an extremely powerful antioxidant. For example, PQQ is able to carry out 20,000 catalytic conversions, compared only 4 for Vitamin C.892 The studies in Parkinson’s Disease prevention and PQQ are particularly interesting. And applicable to neurohackers of any age. We are exposed to pesticides in most of the fruit and vegetables we pick up at the supermarket. And who knows what kind of brain damage we subject ourselves to every day just from the food we eat. In the lab, animals (rats and mice) have a pesticide injected directly into their brain to induce Parkinson’s-like symptoms. In one study, PQQ not only showed a protective effect against pesticide caused brain damage. It actually preserved brain mitochondria near control levels.893 The message here is buy organic food, or supplement with PQQ. And you may be able to avoid getting Parkinson’s Disease later in life. (I do both just to be on the safe side ). How does PQQ feel?

Mitochondria biogenesis means that your body is creating new mitochondria. PQQ increases the number of mitochondria in your brain cells. And throughout your body where energy demands are high. Increasing your body’s mitochondria is one of the anti-aging ‘holy grails’. Boosting these tiny cellular energy power plants can prevent further damage. It can add overall energy to daily life. And maybe even slow down the aging process. Neurohackers report dramatic improvements in mental and physical energy when adding PQQ to their nootropic stack. And I recommend adding CoQ10 for the synergistic effect. PQQ has a cumulative effect and benefits should continue to improve over continued usage. For some the effects are immediate. For others it could take 2 or 3 months of dosing PQQ every day or every 2nd day. PQQ is particularly effective if you’ve suffered mitochondrial damage from using statins. Memory improves and you’ll be able to think things through more easily. Alertness gets a boost. And better vision and less eyestrain if you’re working on a computer or staring at a screen all day. Blood pressure readings could normalize. And you’ll feel refreshed and well-rested when waking up. If you are dealing with Fibromyalgia, you may get some benefit from PQQ with alleviating your chronic pain. The Research PQQ Improves Mood This study in Japan investigate the effectiveness of supplemental PQQ on stress, fatigue, quality of life and sleep. 17 adult male and female subjects took 20 mg of PQQ daily for 8 weeks. Changes in stress, fatigue, quality of life measures and sleep were evaluated. The study showed that vigor, fatigue, tension-anxiety, depression, anger-hostility and confusion improved following administration of PQQ. Measures for quality of life, appetite, sleep, obsession and pain also improved significantly. The volunteers also showed significant improvement in sleepiness at awakening, sleep onset and maintenance, and sleep duration. The researchers concluded that supplementing with PQQ improved sleep quality and duration, mood improved due to less fatigue, and appetite, pain and obsession all showed improvement. And that PQQ is a “useful dietary supplement”.894 PQQ Improves Cognition PQQ is effective on its own in improving brain function. But when it is combined with CoQ10 the results are even more astounding. This synergy was first observed in animal studies. And was further demonstrated in a double-blind, placebo-controlled trial in Japan.

71 middle-aged and elderly volunteers ages 40 – 70 were supplemented with 20 mg per day of PQQ. The result was an improvement on tests of higher cognitive function compared to placebo. Then the research team gave the volunteers 20 mg of PQQ along with 300 mg of CoQ10. And the results in improved cognitive function were even more dramatic. PQQ and CoQ10 are both involved in mitochondrial function. So these results did not come as a big surprise.895 PQQ Boosts Memory Many older adults experience problems with memory and other cognitive functions. And these issues seem to be happening to younger and younger people. As neurohackers, we always ask the question, “Are these declines inevitable?” And to that we say a profound, “No”! In this Japanese double-blind, placebo-controlled trial 65 adults aged 50 – 70 years with forgetfulness were recruited. The volunteers were given 20 mg of PQQ and 100 mg of CoQ10 per day for 24 weeks. The research team found that PQQ taken either alone, or in combination with CoQ10 has the potential to prevent, or even reverse, the decline in cognitive function caused by aging and oxidative stress. The team concluded “PQQ was found to improve not only immediate memory, but also other higher brain functions such as spatial awareness. The effects of PQQ were enhanced when the substance was used with CoQ10.”896 Dosage Notes You get PQQ from some of the food you eat including beans, celery, cocoa, fermented foods (i.e. tempeh, natto), kiwi, papaya, parsley, potatoes, spinach and wine. Babies get it from breast milk. Estimated daily intake of PQQ is 100 – 400 mcg. But it’s unlikely you’re getting enough PQQ from diet alone. And supplementation of this mitochondria generator could help. Clinical studies with humans and animals tell us that 20 mg of PQQ daily is needed to experience cognitive benefit. Side Effects The primary “side effect” of using PQQ in your nootropic stack is - you’ll feel better. You should have more energy and thinking should be clearer and faster. PQQ is non-toxic and supplementation is well-tolerated by most people. Available Forms PQQ comes in table or capsule form 10 mg, 20 mg and 30 mg. But you need to be aware of different forms of PQQ on the marketplace. There is only 1 form available that is produced naturally. And that is BioPQQ® by Mitsubishi Gas Chemical Company of Japan. This company makes PQQ through bacterial fermentation. BioPQQ is licensed to several supplement makers.

Other forms are produced through a chemical synthesis, involving the use of fairly toxic compounds, and have unresolved safety issues. Nootropics Expert® Recommendation PQQ 10 - 20 mg per pay I recommend using PQQ as a nootropic supplement. Your body does not make PQQ on its own. You can get some PQQ from the food you eat. But studies have shown we may not get an adequate supply of PQQ from food sources in our diet. PQQ helps create mitochondria in your brain cells. When cellular energy gets a boost, you can experience better and faster thinking, learning is easier, recall is faster, and you’ll be more resistant to fatigue. PQQ is especially helpful for those suffering from age-related cognitive decline. Studies show it helps stop or reverse brain degeneration with Alzheimer’s and Parkinson’s Disease. Especially in the early stages of the disease. I suggest starting with a dose of 10 - 20 mg daily. And PQQ is a great compliment to a stack including any nootropic. It works particularly well when combined with CoQ10. You need to provide your brain cells with fresh mitochondria and supply neurons with the fuel it is demanding. Or neurons start to break down from the inside. Signs that your lacking adequate PQQ is brain fog, slow thinking, headaches and muscle aches. Age-related cognitive disorders that include muscle control problems may want to up the dose to 30 mg per day. But for a limited time until PQQ blood levels are stabilized. Work with your doctor.

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Pramiracetam Pramiracetam has been shown to boost overall cognition, focus, working- and long-term memory, and learning Pramiracetam (N-[2-[di(propan-2-yl) amino] ethyl]-2-(2-oxopyrrolidin-1-yl) acetamide, CI-879, Pramistar, Neupramir, Remen) is a fat-soluble nootropic in the racetam-class of compounds. Pramiracetam was first synthesized by scientists at Parke-Davis in the late 1970’s. It was first tested with Alzheimer’s patients. Seeing mixed results, the company tried it with major depressive disorder. And licensed Pramiracetam as an orphan drug to Menarini who continued research on using it for dementia. In 1991, the company licensed Pramiracetam to Cambridge Neuroscience Inc. (CNI).897 The nootropic was then tested for restoring cognitive function after stroke or traumatic brain injury. Researchers found that Pramiracetam was up to 30-times more potent than the original Piracetam. In Europe this nootropic is prescribed for the treatment of dyslexia, ADHD, dementia and other memory problems. Brand names for prescription Pramiracetam include Pramistar, Neupramir and Remen. Pramiracetam has gained a reputation in the nootropics community for optimizing cognition. It’s a favorite with students and executives for boosting cognition, focus, memory, and recall. Pramiracetam helps: •

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High Affinity Choline Uptake (HACU): Pramiracetam has been shown to significantly increase HACU in the hippocampus. This action boosts acetylcholine (ACh) use which accounts at least in part for Pramiracetam’s ability to enhance cognition and memory.898 Neurotransmitters: Pramiracetam has a profound effect on the synthesis of the neurotransmitter acetylcholine (ACh).899 ACh is critical for encoding new memories, concentration, cognition and neuroplasticity. Cerebral Blood Flow: Pramiracetam increases nitric oxide (NO) activity in your brain.900 NO acts as a vascular dilator which means it relaxes blood vessels allowing for the freer flow of blood. Increased blood flow delivers more oxygen and nutrients to brain cells promoting better learning and memory.

Pramiracetam was developed by Parke-Davis in the late 1970’s from Piracetam by substituting the amide group with a dipropan-2-ylaminoethyl group. Parke-Davis was once America’s largest and oldest drug maker. It has since been acquired by Pfizer as part of their acquisition of Warner-Lambert in 2000. Parke-Davis has an interesting history and were pioneers in many areas including drugs that affect cognition. Even conducting some research with peyote in the early 1900’s.901 Pramiracetam as a nootropic is legal and sold in many parts of the world as the prescription drug Pramistar, Neupramir, or Remen. In the United States, Pramiracetam is sold as an OTC ‘research compound’, and readily available to the nootropics community.

Pramiracetam shares a unique quality with Coluracetam in the racetam-class of nootropics. Its primary method of action is boosting high affinity choline uptake (HACU) in the hippocampus. It helps increase acetylcholine synthesis and function which helps overall cognition, improved memory and recall, learning, and focus. Pramiracetam has been shown in the lab to not directly influence GABA, dopamine, norepinephrine, or serotonin in the brain.902 So don’t look to Pramiracetam to correct mood and anxiety issues. Pramiracetam does increase nitric oxide activity in your brain. Helping to increase cerebral circulation which improves the efficiency of brain cells needed for motor function, learning and visual function. How does Pramiracetam work in the Brain? Pramiracetam boosts brain health and function in several ways. But two in particular stand out. 1. Pramiracetam improves memory. Several animal and human studies show that Pramiracetam has a significant impact on memory. In this animal study researchers administered Pramiracetam to rats in a one-trial test. This is significant because it proves that Pramiracetam works right out of the gate. It doesn’t take multiple doses, or a couple of weeks to build up in your system. It works on the first day you use it. The scientists found that rats had a significant improvement in retention by using Pramiracetam. And the effect lasted for 24 hours.903 2. Pramiracetam increases high-affinity choline uptake (HACU). Studies have shown that Pramiracetam boosts HACU in the hippocampus. The increase in acetylcholine (ACh) makes more of this neurotransmitter available to neurons for cognitive processing. Increasing attention, mental clarity, memory and verbal skills.904 High affinity choline uptake (HACU) is the uptake of choline in synapses needed for acetylcholine (ACh) synthesis. This is a critical link in the chain of events needed for your brain to make ACh.905 Studies with Pramiracetam and other racetam nootropics like Coluracetam show that boosting HACU increases memory. And even restores memory function in parts of the brain that have been damaged.906 How things go bad As we get older, our brain chemistry and metabolism changes. And it seems these changes are affecting younger and younger people. ↓ Recall, reaction time and learning capacity declines ↓ Acetylcholine receptors decline ↓ Acetylcholine levels decline ↓ Cerebral blood flow declines ↓ Nitric Oxide levels decline

All of these changes are contributing factors to age-related cognitive decline. Early signs of these effects can be seen in poor decision-making, difficulty learning, and even recalling simple things like an important appointment. But even if you’re not concerned with the signs of aging, Pramiracetam can help. Pramiracetam benefits Pramiracetam helps boost acetylcholine (ACh) synthesis and use in your brain and increases cerebral circulation. As a nootropic, Pramiracetam easily crosses the blood-brain barrier.907 And since it is fat-soluble, it must be taken with a healthy fat to ensure absorption. Pramiracetam increases the amount and efficiency of acetylcholine by influencing the high affinity choline uptake (HACU) system in your brain. This increase in ACh can have a profound effect on overall cognition and memory. With Pramiracetam, you’ll find it easier to focus and learning ability will improve. This increase in ACh in your hippocampus helps with logic and understanding complex mathematical and technical subjects if that’s your thing. Increased neuroplasticity from more acetylcholine and improved cerebral circulation affects long-term potentiation.908 So you may find it easier to recall long-forgotten memories. How does Pramiracetam feel? Many neurohackers report that taking Pramiracetam quickly gets your brain firing on all cylinders. There is an intense increase in focus and possibly even a boost in confidence. But once you get accustomed to this laser-like focus, the novelty wears off and you become used to being able to focus at will. Pramiracetam is reported to be great for intense, long study sessions. Or when you face logical, attention-based tasks where you need sharp focus. Like when you’re doing a presentation before the Board, or a group of VC’s. This nootropic makes burning through tedious, arduous tasks that require a level of sustained focus easier, and that would otherwise seem difficult. Others report improved recall ability, fluidity of thought, and ease of verbal communication and numerical calculations. The Research Pramiracetam Normalizes Brain Waves Researchers working with old Fisher-344 rats found that the aged rats had a consistently different EEG profile from young rats. They found slow brain waves were present in both the frontal cerebral cortex

and hippocampus. Theta brain wave activity was missing altogether but was dominant in the brains of young rats. Theta brain waves are associated with creativity, integrative experiences and relief from trauma. Theta waves are commonly experienced by meditators. An “ah-ha moment” is a burst of Theta waves in your brain. This research team found that Pramiracetam normalized brain wave activity in the old rats. And even more interesting was that its older sibling Piracetam did not produce this effect on brain waves. And that tolerance to Piracetam was a problem. While it hasn’t been proven in the lab, this study shows that Pramiracetam would be of benefit to the older generation looking to improve cognitive function.909 Pramiracetam Improves Memory Researchers in Italy investigated Pramiracetam effects on memory, and memory training by a therapist. Types of memory measured were objective memory and metamemory performance. Metamemory is both the inner-knowledge of one’s own memories combined with the processes for formulating new memories with no inner-knowledge. 35 healthy volunteers were chosen with an average age of 64.8 years. 10 subjects received memory training only, 8 received Pramiracetam, 10 received both memory training and Pramiracetam, and the control group received nothing. Results of the study showed that those receiving both memory training and Pramiracetam experienced a significant improvement in memory. Followed by the Pramiracetam group. The memory training-only group and control group scored the lowest. The research team concluded that Pramiracetam significantly improves memory. And the addition of memory training to Pramiracetam has an even more profound effect of both types of memory measured.910 Pramiracetam Enhances Cognition This double-blind placebo-controlled study worked with young males who suffered cognition problems due to brain injuries. The men had problems with memory and recall. One group received 400 mg of Pramiracetam daily for 18 months. And the other group a placebo. Memory was measured during the trial and for 1-month after Pramiracetam was discontinued. The researchers found that Pramiracetam produced a significant improvement in cognition, memory and recall.911 Dosage Notes Recommended Pramiracetam dosage is 250 - 400 mg up to 3-times per day. One Pramiracetam dose in the morning, and one in the early afternoon, and if you’re doing a 3rd dose do it later in the afternoon.

Pramiracetam is fat-soluble so for best results take it with a quality fat like extra virgin, cold-pressed unrefined coconut oil, MCT oil or olive oil. If you don’t take Pramiracetam with supplemental fat, don’t expect much of an improvement in cognition. Pramiracetam is one of two racetams (the other is Coluracetam) that have a profound effect on high affinity choline uptake (HACU). This means it will help your brain make more acetylcholine (ACh) and boost the use of ACh. Acetylcholine is synthesized from the available choline in your brain. Which means for best results you should stack Pramiracetam with supplemental choline. We recommend a good quality choline source like Alpha GPC or CDP-Choline. Pramiracetam tastes particularly nasty. So you may want to get capsules or tablets rather than powder (unless you’re making your own capsules). DO NOT try to take Pramiracetam sublingually because it will literally burn the lining of your mouth. Side Effects Pramiracetam is non-toxic. So is considered well-tolerated and safe. As with many of the racetams, Pramiracetam can cause headaches because it boosts the use of acetylcholine in your brain. Choline supplements like Alpha GPC or CDP-Choline can help you avoid this side effect. Many neurohackers also find that stacking Pramiracetam with a choline supplement boosts the effect with improved memory and cognition. And this is supported in several research studies. Some users report that Pramiracetam blunts their emotions. Decisions when it comes to life and work issues are logic-based rather than emotional. This can be good or bad depending on the situation of course. You could call it “emotional objectivity”. Available Forms Pramiracetam is sold in tablet, capsule, and powder form. Tablets and capsules are usually 250 or 300 mg each. In Europe, Pramiracetam is a prescription drug under brand names Pramistar, Neupramir, or Remen. Nootropics Expert® Recommendation Pramiracetam 250 - 400 mg up to 3-times per day I recommend using Pramiracetam as a nootropic supplement. Your body does not make Pramiracetam on its own. So to get its benefits you must take it as a supplement. Pramiracetam is especially helpful for those suffering from age-related cognitive decline. Its boosts high affinity choline uptake (HACU) which means more acetylcholine (ACh) is available in your brain.

Providing a significant improvement in cognition and memory. Pramiracetam is also particularly useful to students and executives who want to boost cognition, focus, learning and memory. Pramiracetam is fat-soluble so stack it with a good quality fat like coconut oil, olive oil or MCT oil. You should use Pramiracetam with a choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain. You can safely boost daily intake of Pramiracetam to 1500 mg if needed. But most find that lower doses are more effective.

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Pterostilbene Pterostilbene is a very potent antioxidant, stimulates Brain-Derived Neurotrophic Factor, promotes neuroplasticity, is anti-anxiety, boosts dopamine, and helps cognition, learning and memory Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, PTE) is a naturally derived polyphenol antioxidant found in blueberries, grapes, and in the bark of the Indian Kino Tree. Pterostilbene, a naturally occurring dimethylether analog of resveratrol, is a phytoalexin that, like resveratrol, is made by plants to fight infection, insect infestation, heat and ultraviolet exposure.912 Pterostilbene and resveratrol are both ‘stilbene’ polyphenols. But Pterostilbene is much more bioavailable than resveratrol. It rapidly crosses the blood-brain barrier, and stays in your body much longer than resveratrol (half-life of 105 mins. vs. 12 mins.).913 Pterostilbene shows 80% bioavailability while resveratrol only has 20% bioavailability.914 Pterostilbene is gaining a reputation in the nootropics community for controlling brain inflammation, boosting dopamine, helping reverse cognitive decline and fighting brain cell aging. Pterostilbene helps: •

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Neuroplasticity. Pterostilbene increases hippocampus neurogenesis, boosts insulin-like growth factor-1 (IGF-1), and modulates the receptor kinase pathway that is central in the learning and memory process. Increasing neuroplasticity in the hippocampus improves learning and memory functions.915 Neuroprotectant. Pterostilbene is a potent antioxidant and anti-inflammatory. It reduces reactive oxygen species (ROS) and increases the antioxidant glutathione and superoxide dismutase (SOD).916 Crucial to overall brain health, maintaining signaling pathways and leading to improved learning and memory. Brain-Derived Neurotrophic Factor (BDNF). Pterostilbene has been shown in clinical trials to elevate BDNF in the hippocampus. Improving learning and memory.917

Pterostilbene and resveratrol are both ‘stilbene’ polyphenols. And both boost cognition, learning and memory. But Pterostilbene works differently than Resveratrol. And is not a replacement for Resveratrol. Here’s why… Resveratrol has been getting a lot of press lately because of its ability to boost learning, memory and cognitive power. But Pterostilbene is much more bioavailable than resveratrol. And may be the preferred polyphenol to add to your nootropic stack. Pterostilbene stands out because of its structural differences from Resveratrol. Pterostilbene has two methoxy groups and one hydroxyl group. Resveratrol has three hydroxyl groups. This combination in Pterostilbene improves lipophilicity which means it can dissolve in fats, oil and lipids. Lipids are what makes up the shell or membrane encasing each one of your cells.

So Pterostilbene can more easily cross through your cell walls. In fact, several published studies refer to Pterostilbene as having much better bio-activity than Resveratrol. You can easily add Pterostilbene to your diet. It’s found in blueberries, cranberries, sparkleberries, lingonberries, grapes, and in the bark of the Indian Kino Tree. But to get the therapeutic benefits of Pterostilbene, a preferred way of getting this potent antioxidant is to take it as a supplement. Pterostilbene has been shown to prevent the loss of the neurotransmitter dopamine from memory centers in your brain. Supplementing with PTE raises its levels in your hippocampus which is where memory is processed. Pterostilbene also has the effect of caloric restriction on cells which profoundly effects gene expression. This tricks your body into improving memory because it’s thinking there is food scarcity. And it provides an adaptive response. The polyphenol Pterostilbene increases neuroreceptor sensitivity which improves neuronal signaling. And PTE promotes the formation of new synaptic connections which boosts neuroplasticity. Improving long-term potentiation resulting in formation of long-term memories. How does Pterostilbene work in the brain? Pterostilbene boosts brain health in several ways. But two in particular stand out. 1. Pterostilbene mimics caloric restriction. Restricting calories by fasting has been implicated in increased synaptic plasticity resulting in improved learning. Scientists determined that this enhancement in synaptic plasticity was caused by increased brain cell signaling. The signaling increase is mediated by CREB (cAMP response element binding protein).918 CREB has a proven role in neuronal plasticity and long-term memory formation in the brain. And has been shown to be critical in the formation of spatial memory.919 In several studies, Pterostilbene has been shown to modulate gene expression. PTE up-regulates those genes that stimulate apoptosis (programmed cell death). And down-regulate those genes that allow cancer cells for example, to invade and metastasize.920 And this gene modulation is linked to increases in CREB and Brain-Derived Neurotrophic Factor (BDNF). An increase in BDNF helps long-term potentiation needed for the development of long-term memory. In this study, researchers supplemented aging animals with blueberry extract for 12 weeks. This extract contained PTE. Spatial working memory tasks emerged within 3 weeks of supplementation. And persisted for the remainder of the testing period. This memory enhancement correlated with the activation of CREB. And increases in brain-derived neurotrophic factor (BDNF) in the hippocampus. In fact, PTE was implicated in the entire chain of the

ERK-CREB-BDNF signaling pathway that boosts memory.921 2. Pterostilbene boosts dopamine. But it increases dopamine in kind of a ‘back door’ approach. We have plenty of research showing that neurodegeneration is caused by oxidative stress. And that anti-oxidants can stop and even reverse damage to neurons. Potentially leading to an increase in the release of important neurotransmitters like dopamine. PTE is a potent antioxidant. One study done a Tufts University in Boston investigated stilbene compounds like PTE and their effect on reversing the effects of aging. The researchers used 344 Fisher rats and gave them either a low (0.004%) or a high (0.016%) concentration of Pterostilbene. Results from this study showed that PTE was effective in reversing cognitive deficits. And Pterostilbene increased dopamine release. A boost in working memory correlated with Pterostilbene levels in the hippocampus.922 How things go bad As we get older, the chemistry in our brain cells and energy metabolism changes. ↓ Neurons and synapses degenerate ↓ Recall, reaction time, memory, and mood diminish ↑ Anxiety levels increase ↓ Neurotransmitter levels decline ↓ Oxidation damages brain cells All of these age-related changes are contributing factors to the neurodegenerative diseases of aging including Alzheimer’s, Parkinson’s and dementia. But even if things haven’t degenerated to such a debilitating level, PTE can help. Pterostilbene benefits Pterostilbene helps improve memory and provides neuroprotection through different mechanisms of action than most other nootropics in a typical stack. PTE works primarily through gene expression. Easily passing through cell walls, PTE modulates genes that influence other proteins, mitochondria and even cell DNA. We talk a lot about apoptosis (programmed cell death) as a negative event in nootropic circles. But the reality is that apoptosis is an integral part of a healthy brain. Pterostilbene stimulates apoptosis to make way for healthy new cells to be born (neurogenesis). And helps down-regulate invaders like cancer cells. Preventing them from invading healthy brain tissue and metastasizing.923 Some supplement makers are mistakenly marketing their Pterostilbene as an “upgraded-version” of

Resveratrol. But the research shows Pterostilbene and Resveratrol work together to boost cognitive health. Resveratrol works at the beginning of the cascade of neurochemical events that activates genes leading to cognitive benefits. And Pterostilbene provides its gene expression effects in the downstream portion of this molecular cascade. Pterostilbene has a kind of ‘reverse effect’ on boosting dopamine. Rather than directly increasing dopamine levels like some nootropics, PTE prevents the loss of dopamine in brain memory centers. This is not nearly as strange as it sounds. Because this mechanism of action is similar to how Ritalin works as a stimulant. By preventing the uptake of dopamine by neuroreceptors, Ritalin keeps more dopamine available for increased alertness, cognition and memory formation. PTE prevents brain injury from lack of blood flow and could have profound applications in the recovery from stroke. This effect could be beneficial even in healthy brains who suffer from brain fog due to poor cerebral circulation. Pterostilbene provides well-documented antioxidant activity.924 Affecting neuroreceptor sensitivity for improved neural signaling. PTE even promotes new synaptic connections between neurons. Improving neuroplasticity leading to better learning and memory.925 How does Pterostilbene feel? Neurohackers report that supplementing with Pterostilbene boosts energy levels, provides clearer thinking and improved mood. Taken before an anxiety-producing event, PTE takes the edge off with no sedation. Aging baby boomers report feeling younger after using Pterostilbene. They feel more alert, less joint and lower back pain, more energy, less anxiety, and better focus. The Research We have hundreds of studies talking about the benefits of Resveratrol. But mostly animal studies for Pterostilbene. So just bear in mind that life is not a clinical study. Take what you can from this article on PTE and read user reviews on some of the major sites. Then add Pterostilbene to your stack and see if it makes a difference in your life. If you notice a difference, please bookmark this chapter, and tell your friends about it. And help a brother (or sister) out. Pterostilbene Reduces Anxiety A study at the University of Mississippi investigated using Pterostilbene for anxiety disorders. Using mice, the team administered PTE in 1 – 10 mg/kg doses. Measuring the effects of each dose for its anxiolytic effect.

To measure this mood effect, the team evaluated decreases in extracellular regulated kinase 1 and extracellular regulated kinase 2 in the mice. These signaling pathways are involved in mood modulation in both animals and humans.926 The research team found that no anxiolytic (anti-anxiety) activity was found at higher doses of Pterostilbene. But at lower doses of PTE (1 and 2 mg/kg), there was significant anti-anxiety activity in the brain. And unlike standard anti-anxiety drugs, there was no impairment of motor movement. In other words, there were no negative physical effects of using PTE for anxiety issues. The team concluded that, “These results suggest that Pterostilbene has the potential for therapeutic drug development for anxiety disorders.”927 Pterostilbene Improves Cognition Recent studies have shown that Pterostilbene and Resveratrol protect against age-related diseases like Alzheimer’s. So this study looked at comparing the two ‘stilbenes’ to find out which was more effective in improving cognitive deficits, and Alzheimer’s pathology. The pathology of Alzheimer’s can be broken down into; cellular stress, inflammation and other pathology markers known to be altered in the disease. Researchers at Case Western Reserve University in Cleveland, Ohio looked at the mechanism of action behind each of these pathology markers. They used SAMP8 mice which are bred to model age-related Alzheimer’s. Two months of a Pterostilbene diet (but not Resveratrol) improved radial arm water maze function in these mice compared to controls who were fed a standard mouse diet. This is where it gets good. Markers of cellular stress, inflammation, and Alzheimer’s pathology were all positively modulated by Pterostilbene. The team concluded that “diet-achievable doses of Pterostilbene is a potent modulator of cognition and cellular stress”. Much better than Resveratrol. The research team said that this success in improving cognition with Pterostilbene was due to its ability to increase peroxisome proliferator-activated receptor alpha (NR1C1) expression. This particular receptor is encoded by the pPARA gene. And as you may recall from earlier in this chapter, Pterostilbene’s big claim to fame is ‘gene expression’ and modulation. The team also noted that PTE works better than Resveratrol because of its increased ability to cross the blood-brain barrier. And superior bioavailability.928 Pterostilbene is one of the only nootropics that improves cognition directly by modifying genes (gene expression). Pterostilbene Protects Neurons Blueberries have been reported to provide long-term neuroprotective effects. But researchers in China

wanted to dig deeper to determine what in blueberries provided this benefit. Was it Pterostilbene? The research team dosed mice with 2.5 – 80 mg/kg of PTE for 3 days. Then induced a middle cerebral artery occlusion for 90 minutes. In other words, they gave the mice a stroke. The team gave the mice another dose of PTE immediately after the stroke, at 1 hour and at 3 hours. The team found the most therapeutic window for neuroprotection was 1 hour after the stroke dosed at 10 mg/kg. Pterostilbene improved motor function, eliminated blood flow disruption, increased neuron survival, and reduced cell apoptosis (cell death). The team concluded that you could protect the brain from stroke using Pterostilbene. And this neuroprotective effect of Pterostilbene was associated with preventing oxidative stress and neuron death.929 Dosage Notes Pterostilbene is found in small quantities in some plant foods. A cup of blueberries for example, contains only about 20 mcg of Pterostilbene. But even in small amounts, Pterostilbene is believed to provide some of the benefits talked about in this chapter. Based on all of the published animal studies, the recommended daily dose of Pterostilbene is 50 mg for cognitive benefit. Side Effects The primary “side effect” of using Pterostilbene in your nootropic stack is - you’ll feel better. You should have more energy and thinking should be clearer and faster. And Pterostilbene provides an antianxiety effect. Pterostilbene is non-toxic and supplementation is well-tolerated by most people. One randomized, double-blind placebo-controlled trial conducted at the University of Mississippi School of Pharmacy did an analysis of safety in humans. 80 subjects were divided into four equal groups. Each group received either; 125 mg of Pterostilbene twice daily, the 2nd group 50 mg twice daily, the 3rd group 50 mg plus 100 mg of grape extract twice daily, and the 4th group a matching placebo twice daily. The trial ran for 6-8 weeks. The researchers concluded that “Pterostilbene is generally safe for use in humans up to 250 mg per day”.930 But the benefits from Pterostilbene follow a bell-curve. With little or no benefit at lower doses, optimal benefits around 50 mg per day, and no benefit again at much higher doses. Like other nootropics, more of Pterostilbene is not necessarily better.

Available Forms Pterostilbene comes in tablet or capsule form and is available by several well-known supplement makers. Some pre-made nootropic stacks include PTE in their formula. pTeroPure® is a branded form of Pterostilbene derived from blueberries. And marketed as yielding 99.9% purity. You can also get Pterostilbene from blueberries. But you’d have to eat a lot of berries to get your quota of 50 mg per day. Blueberry extract supplements contain Pterostilbene. But do not typically indicate exactly how much is in the extract. Nootropics Expert Recommendation Pterostilbene 50 mg per pay I recommend using Pterostilbene as a nootropic supplement. Your body does not make Pterostilbene on its own. You can get some Pterostilbene from blueberries and a few other fruits. But studies have shown we may not get an adequate supply of Pterostilbene from food sources in our diet. Especially if you don’t eat a lot of fruit every day. Pterostilbene has been used in Ayurvedic medicine for thousands of years as a “blood tonic”. Pterostilbene helps protect neurons and boosts other antioxidants that shield your brain cells from oxidative stress. Protecting brain cells in memory centers of the brain help boost dopamine. Resulting in better alertness, learning and memory. The boost in memory and learning also comes from Pterostilbene’s ability to promote neuroplasticity. And PTE helps maintain cerebral circulation by protecting brain blood vessels from lack of oxygen, and oxidative stress. Pterostilbene is especially helpful for those dealing with anxiety. PTE provides an anxiolytic effect without the sedation you’d normally get from using anti-anxiety drugs. I suggest starting with a dose of at least 10 mg daily. And Pterostilbene is a great compliment to a stack including any nootropic. It works particularly well when combined with Resveratrol.

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Quercetin Quercetin is used for allergies, arthritis pain, athletic muscle soreness, memory, a leaky gut, and reducing the symptoms of COVID-19 Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is one of the most abundant flavonoids present in over twenty plant and fruit categories. Quercetin is known for its anti-inflammatory properties. It’s used to lower blood pressure, control obesity, lower cholesterol, and protect against heart attacks and stroke.931, 932 Quercetin is commonly found in foods such as capers, buckwheat, radish leaves, dill, cilantro, onions, radicchio, watercress, kale, blueberries, cranberries, plums, red wine, and black tea. And is found in some herbal nootropic supplements including Ginkgo Biloba and St. John’s wort. As one of the most abundantly consumed flavonoids in your diet, it is estimated that an average person consumes only 0 – 30 mg of Quercetin every day. The name Quercetin comes from a Latin word “Quercetum”, which means Oak Forest.933 Quercetin is yellow in color and is poorly soluble in hot or cold water, but easily soluble in alcohol and fats. Quercetin cannot be produced in your body and must be obtained from food or as a supplement.934 It can be found in citrus fruits, green leafy vegetables, seeds, buckwheat, nuts, flowers, barks, broccoli, olive oil, apples, onions, green tea, red grapes, red wine, dark cherries, and berries. Quercetin is one of the popularly used bioflavonoids for the treatment of metabolic and inflammatory disorders. Hundreds of in-vitro and animal studies, and a few human studies have been conducted to study the effects of Quercetin. Research shows its antioxidant properties are potent enough to treat infections, inflammation, neurodegeneration, and even certain types of cancers.935 Quercetin has also recently been found to be beneficial in reducing the symptoms of COVID-19. A Chinese study showed that Quercetin bound with the spike protein in the coronavirus, reducing its ability to infect cells.936 How does Quercetin Work in the Brain? Quercetin boosts brain health and function in several ways. But two in particular stand out. 1. Neuroprotection – Several in-vitro studies show that Quercetin is a potent antioxidant. And is capable of scavenging free radicals and protecting the brain from damage caused by oxidative

stress.937 Quercetin’s antioxidant property is mainly due to its effect on glutathione (GSH), enzymatic activity, and reactive oxygen species (ROS) caused by environmental factors and other toxins.938 2. Improve memory – Due to its ability to scavenge free radicals, Quercetin has the potential to reverse cognitive deficits and may improve memory.939 One animal study using mice showed increased learning and memory in the mice who were administered Quercetin with no improvement in the control animals.940 How things go bad Natural brain aging often results in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s Disease. But even if you don’t experience neurodegenerative disease as you get older, human aging naturally results in: ↓ Chronic inflammation ↓ Poor memory ↑ High cholesterol and triglycerides ↑ Increased belly fat ↓ Insulin resistance ↓ Mitochondrial insufficiency and dysfunction ↓ Neurodegeneration Adding Quercetin to your nootropic stack may help prevent neurodegenerative disease and the symptoms typically associated with aging. Quercetin benefits Quercetin has the unique ability to increase claudin-4 which seals Tight Junctions and healing a leaky gut or leaky blood-brain barrier.941 Quercetin is a potent antioxidant and may protect your brain from oxidative stress. In 2014, scientists administered Quercetin to rats within 48 hours of the animals suffering a brain edema. The study showed a high dose of Quercetin administered 48 hrs. after the stroke helped reverse neurobehavioral deficits that were the result of a brain edema (swelling due to fluid build-up). Including a significant reduction in oxidative stress, and a reduction in cellular apoptosis.942 Quercetin protects the brain against toxins by activating the brain’s natural immune system.

Another study in 2013 was conducted to deduce the effect of Quercetin on lead-toxicity. And it showed that Quercetin significantly prevented lead induced neurotoxicity, and oxidative stress.943 And studies with animals also demonstrated Quercetin’s ability to help preserve brain activity in degenerative diseases like Parkinson’s and Alzheimer’s. These studies show that Quercetin has therapeutic potential because it can inhibit Aβ aggregation, and tau phosphorylation. And inhibits acetylcholinesterase which in turn increases acetylcholine levels.944 Quercetin may also boost testosterone levels. UGT2B17 is an enzyme that converts testosterone into testosterone glucuronide – which is then excreted out of your body through urine.945 Quercetin has been shown to inhibit UGT2B17 activity by as much as 72% according to lab studies. Which means supplementing with Quercetin as a nootropic may slow down it’s excretion. And boost levels of testosterone in your blood. Quercetin also inhibits aromatase which is the enzyme that converts testosterone into estrogen.946 How does Quercetin feel? Some of the most recent comments by Quercetin users report a significant reduction in COVID-19 symptoms. Those infected with the virus reported using Quercetin with Vitamin C, Vitamin D, and zinc. Their breathing was easier, and this combo helped them recover faster. And this is beginning to be backed by clinical studies as well.947 Many neurohackers using Quercetin report a dramatic improvement in seasonal allergy symptoms. Others claim Quercetin helps reduce muscle soreness after a workout. And arthritis pain is reduced. Many people said using Quercetin consistently reduced their cold symptoms faster. Some suffering from allergies say Quercetin is a great alternative to antihistamines without the drowsy side effects caused by these drugs. Overall, Quercetin users said they were able to breathe easier, experienced less pain, and had more power and stamina. Quercetin Clinical Research Quercetin improves athletic performance A double-blind, placebo-controlled clinical trial was conducted in 2013 in Iran with 26 badminton players. One group was given Quercetin 1000 mg per day for eight weeks. And the control group given a placebo. The aim of the study was to determine how Quercetin supplementation affects performance, muscle damage and body muscle in badminton players.

Lactate concentration, body fat percentage and VO2 max did not show any significant difference after 8 weeks in either group. But there was a significant difference in time to exhaustion in the Quercetin group. But not in the placebo group. The researchers concluded “that intake of Quercetin may improve endurance exercise performance but may not reduce the body fat percentage”.948 Quercetin reduces oxidative stress Several animal studies have been conducted to evaluate Quercetin’s effect on oxidative stress. In one study, oral Quercetin (0.5 -50 mg/kg) was shown to protect rodents from oxidative stress and disorders associated with it.949 Quercetin also protects against the neurotoxicity of several heavy metals. Three animal studies were conducted on the impact of Quercetin on toxicity induced by lead, methylmercury, and Tungsten. The results indicated that Quercetin functioned as an effective protector against metal-induced neurotoxins. And could be considered a potent therapeutic intervention to cure cognitive deficits induced by these metals.950, 951, 952 Quercetin reduces inflammation High fat diets cause oxidative stress which may lead to neurodegenerative disease. In one study, a test group of mice were fed high fat diets and given Quercetin. The scientists found that Quercetin reduced the cognitive impairment induced by the high fat diet.953 Quercetin has been shown to improve neuronal functional recovery in rats affected with intracerebral hemorrhage (ICH) by inhibiting inflammatory response and apoptosis and promoting nerve function restoration.954 Recent studies show that Quercetin reduces the symptoms of Alzheimer’s disease and other age-related cognitive disorders.955 Quercetin for COVID-19 Although the research is limited, the few studies that are present on Quercetin’s ability to reduce the symptoms of the novel Coronavirus indicate it has a significant capability to interfere with the replication of the virus.956 Quercetin exhibits a wide range of antiviral properties which can intervene in every step from virus entry to replication, to protein assembly. The impact of Quercetin can be further enhanced through the co-administration of vitamin C and zinc.957

Quercetin Recommended Dosage The recommended nootropic dosage for Quercetin is 500 mg up to twice per day. Quercetin dosages of 1,000 mg, and on the advice of your doctor, up to 3,000 mg per day to reduce COVID-19 symptoms. Note that this is short-term use only at such elevated dosages. Your daily intake of Quercetin from food in a typical Western diet is estimated to range between 0 – 30 mg per day. Quercetin as a supplement has low bioavailability because it does not easily cross the intestinal wall.958 Poor bioavailability is why many Quercetin supplements include other compounds like Vitamin C, bromelain, or other digestive enzymes to help boost absorption. A more recent development shows increased absorption of Quercetin when attached to a phospholipid complex made from lecithin called Phytosome®. Quercetin Phytosome® has been shown to be 20-times more bioavailable than Quercetin on its own.959 Research also shows Quercetin has a synergistic effect when combined with other flavonoid supplements, such as resveratrol, genistein, and catechins.960 Quercetin Side Effects Quercetin is non-toxic and is considered well-tolerated and safe when used at recommended dosages. Supplementing with more than 1000 mg of Quercetin per day may lead to symptoms like stomach aches, headaches, and tingling sensations. Talk to your doctor before taking the supplement if you are pregnant or breastfeeding. Quercetin inhibits aromatase so if you’re being treated for breast cancer – talk to your doctor before supplementing with Quercetin. And animal studies show that high doses of Quercetin can have a negative effective on sperm quality and sperm count in males. But only when coupled with elevated oxidative stress. This hasn’t been proven in humans but it’s worth keeping in mind if you’re having fertility problems.961 Type of Quercetin to Buy Quercetin as a nootropic is available in capsules and bags of powder. You’ll see several brands offering Quercetin + Bromelain because adding a digestive enzyme helps its bioavailability. And the latest is Quercetin Phytosome® which is Quercetin combined with lecithin-derived phospholipids from sunflower to cross the gut barrier more easily. Nootropic Expert® Recommendation

Quercetin 500 mg up to twice per day I recommend supplementing with Quercetin as a nootropic supplement. Your body does not make Quercetin on its own. So, to get its benefits you must take it as a supplement. Or rely on the small amount you get from food. Quercetin is especially helpful for those suffering from allergies, arthritis pain, muscle soreness after a workout, or a cold. Quercetin seems to be effective according to new clinical studies and several user reviews for reducing the severity of symptoms associated with COVID-19. NOTE: anecdotal evidence of using Quercetin to reduce COVID-19 symptoms requires dosages of 1,000 mg and up to 3,000 mg per day until symptoms are gone. Quercetin is non-toxic and is considered well-tolerated and safe when used at recommended dosages. See the “Side Effects” section for more precautions before supplementing with Quercetin. Since Quercetin in its pure form is not easily absorbed by your digestive system, choose a Quercetin supplement combined with Bromelain, Vitamin C, or Quercetin Phytosome®. Quercetin as a nootropic seems to be effective starting at 500 mg per day. Dosages above 1,000 mg per day is not recommended for long-term use. Unless specified by your doctor.

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Resveratrol Resveratrol is a potent antioxidant, boosts BDNF, increases cerebral circulation, improves energy and memory, and potentially promotes longevity Resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a polyphenol stilbenoid and phytoalexin that certain plants produce in response to stress, such as injury or fungal infection. Resveratrol is a naturally occurring compound found most famously in red wine. Some speculate that the Resveratrol found in red wine accounts for the “French Paradox”. And how the French can dine on baguettes, cheese, paté and pastries. While avoiding putting on weight and living longer. Recent research may soon lead the nootropics community to classifying Resveratrol as an Ampakine nootropic. With some rather profound neuroprotective effects in the brain. Resveratrol is gaining a reputation among neurohackers for controlling brain inflammation, boosting dopamine, helping reverse cognitive decline and fighting brain cell aging. Resveratrol helps Brain-Derived Neurotrophic Factor (BDNF). Higher levels of BDNF are associated with increased intelligence, mood, productivity and memory. And decreased risks of neurodegenerative diseases like Alzheimer’s and Parkinson’s. Resveratrol increases BDNF in your hippocampus. Resveratrol is a neuroprotectant. Resveratrol protects your brain by boosting the production of the enzyme heme oxygenase which protects against oxidative stress.962 Resveratrol shields mitochondria from injury during interruptions in blood flow such as a stroke.963 And Resveratrol prevents the release of toxic glutamate during a stroke.964 It even protected the brain when administered 6 hours after a stroke.965 Resveratrol improves cerebral circulation. Resveratrol increases blood flow in your brain. Improving your brain’s blood flow increases oxygen and nutrient levels. Providing your brain with the fuel it needs for optimized cognition. Initial research on Resveratrol led researchers to believe that the compound works by mimicking calorie restriction and decreasing chronic inflammation. As soon as word got out about the first clinical studies at Harvard Medical School, red wine and Resveratrol were soon christened the new “Fountain of Youth”. But Dr. David Sinclair who led the Harvard study says, “You would need to drink a hundred to a thousand glasses of red wine to equal the doses that improve health in mice.”966 However, more research has revealed some rather profound benefits to adding Resveratrol to your nootropic stack. Several human studies show that Resveratrol can increase cerebral circulation, protect against heart disease, and increase insulin sensitivity in diabetics.

Even more studies in animals have shown that Resveratrol can reduce depression, treat addictions, protect against memory loss, is anti-anxiety, reduces plaques in Alzheimer’s disease, improves learning, memory and mood, protects the brain from stroke and shields from hearing loss. Resveratrol is found in red wine, blueberries, cranberries, raspberries, bilberries, grapes, peanuts, pistachios, cocoa, and dark chocolate.967 Here we’re going to dig into how Resveratrol helps your brain. Some of this is going to get a little geeky, so stay with me here… How does Resveratrol work in the brain? Resveratrol boosts brain health in several ways. But two in particular stand out. 1. Resveratrol improves memory. Resveratrol is an inhibitor of enzyme PDE4 (Phosphodiesterase4). PDE4 inhibitors have been shown to be memory enhancers.968 Studies demonstrate that when you inhibit PDE4, you raise levels of cAMP in the brain.969 cAMP-dependent pathways in the brain activate AMPK (AMP-activated protein kinase).970 This effect of activating AMPK has a number of implications. First, this would make Resveratrol an Ampakine nootropic similar to some of the racetams. Second, studies show that AMPK is activated by increases in the cellular AMP/ATP ratio. This helps preserve cellular energy. And would account for at least some of Resveratrol’s neuroprotective properties.971 This same study at the Washington University School of Medicine in St. Louis, Missouri demonstrated that Resveratrol combined with the nootropic ALCAR increased neurite growth which would have a profound effect on boosting memory. And Resveratrol also stimulated mitochondrial biogenesis. The researchers concluded, “These findings suggest that neuronal activation of AMPK by Resveratrol could affect neuronal energy homeostasis and contribute to the neuroprotective effects of resveratrol.” 2. Resveratrol boosts BDNF. Brain-Derived Neurotrophic Factor (BDNF) has been called “Miracle-Gro for the brain” by Harvard Neuropsychiatrist John Ratey. When BDNF is released, nerve cells connect to other cells or their synapses. As brain cells “fire together”, they “wire together”. And this is how new neural networks are formed and consolidated to create memory. Researchers in Iran administered Resveratrol to rats for 30-days. The team was looking at the effects of Resveratrol on the abundance of mRNA encoding Brain-Derived Neurotrophic Factor in the hippocampus. The team measured levels of BDNF in the rat brains and found that Resveratrol elevated the level of BDNF in the hippocampus of these rats. And concluded that the neuroprotective effects of Resveratrol are due to its ability to boost BDNF mRNA.972 How things go bad

As we get older, the chemistry in our brain cells and energy metabolism changes. ↓ Neurons and synapses degenerate ↓ Recall, reaction time, memory, and mood diminish ↓ Cerebral circulation decreases ↓ Neurotransmitter levels decline ↓ Oxidation damages brain cells All of these age-related changes are contributing factors to the neurodegenerative diseases of aging including Alzheimer’s, Parkinson’s and dementia. But even if things haven’t degenerated to such a debilitating level, Resveratrol can help. Resveratrol benefits Resveratrol is an antioxidant polyphenol which are present in foods like red wine, green tea, apples, berries, pomegranates, and dark chocolate. Polyphenols are among the most effective natural ways to combat aging. And to prevent the health issues that often lead to cardiovascular and neurodegenerative disease. Resveratrol helps prevent free radical damage to brain cells. Oxidative damage to brain cell membranes causes deterioration. And eventually leads to premature cell death (apoptosis). Resveratrol has the unique ability to modulate cell apoptosis. And promotes cell death only in instances where your brain would be healthier with fresh, new cells. Resveratrol promotes neurogenesis. Resveratrol inhibits the PDE4 enzyme that raises levels of cAMP in your brain. Much like Luteolin (Artichoke Extract) in the CILTEP stack. cAMP-dependent pathways in the brain activate AMPK which in turn energize brain cells, and boost memory. Resveratrol helps boost cerebral circulation, and Brain-Derived Neurotrophic Factor (BDNF). BDNF helps new neural networks to form which is the basis for memory formation. How does Resveratrol feel? Research shows that Resveratrol can: • • • • •

Improve memory by inhibiting PDE4 in the brain (which boosts cAMP activity) Tame inflammation in the brain Boost cerebral blood flow for more oxygen and nutrients to fuel brain cells Increase BDNF helping new neural networks to form for memory consolidation Neuroprotective qualities that prevent damage to brain cells

Resveratrol quickly enters your brain after you take it. Once in your brain, it inhibits PDE4 which boosts cAMP activity. cAMP is involved in the Long-Term Potentiation process of preserving

memories. Inhibiting PDE4 and boosting cAMP also makes the effect of normal dopamine production more effective. Boosting processes in this stream of chemical reactions in the brain increases learning and memory. Without the side effects of stimulating dopamine production through the use of drugs like Adderall or Ritalin. Neurohackers report the effects of Resveratrol can be subtle. But you don’t want to take it later in the afternoon or it could affect your sleep. You may experience improved mood and motivation, increased ability to study, increased ability to retain information and improved long-term memory. The Research As a young neurohacker, you may not be concerned about the horrors of a disease like Alzheimer’s. Yet several clinical studies make the case for using Resveratrol to boost your memory. And to avoid ever having to be concerned about this debilitating disease. 84,767 Americans die every year from Alzheimer’s disease. And more than 230,000 suffer from dementia severe enough to require nursing home care.973 The Alzheimer’s Association estimates that more than 5 million Americans are living with this disease. And you have a 1 in 3 chance of developing Alzheimer’s or another dementia in your lifetime.974 Now that I have your attention, let’s look at some clinical studies on using Resveratrol to prevent Alzheimer’s and dementia. Resveratrol Protects Against Alzheimer’s Some of Resveratrol’s neuroprotective ability comes from its ability to interfere with the cascade of events arising from an accumulation of abnormal proteins called amyloid-beta. Amyloid-beta causes oxidative stress and inflammation that damages brain cells. Especially in memory centers in the brain. Hence the reason why Alzheimer’s causes such profound memory loss. A study conducted at the Litwin-Zucker Research Center for the Study of Alzheimer’s Disease in New York looked at the cascade of events leading up to Amyloid-beta accumulation that causes much of the problem with Alzheimer’s. The research team demonstrated how Resveratrol activates several metabolic sensors, including AMPK (AMP-activated protein kinase). AMPK signaling controls Amyloid-beta metabolism. So Resveratrol activates AMPK which reduces levels of Amyloid-beta deposits in the cerebral cortex.975 Another study in Italy showed how Resveratrol prevents β-amyloid aggregation by scavenging oxygen free radicals and inducing protective enzymes such as heme oxygenase. Again preventing the build-up of deposits causing Alzheimer’s.976 More recent studies show that Resveratrol can prevent Amyloid-beta proteins from clumping together

into small collections of individual molecules called oligomers. This action alone has a profound effect on preventing Amyloid-beta damage and preventing Alzheimer’s.977 And one more study, again about Resveratrol’s ability to activate AMPK and reduce Amyloid-beta build-up, shows that Resveratrol crosses the blood-brain barrier. And stays in the brain to do its magic. Verifying that using Resveratrol as a nootropic is an effective cognitive enhancer.978 Resveratrol Improves Memory The research team at the Max Planck Institute for Human Cognitive and Brain Sciences investigated the effect of Resveratrol on brain function and memory in healthy overweight older adults. 23 people aged 50 – 75, took 200 mg of Resveratrol daily for 26 weeks. The control group of 23 subjects took a placebo. Memory tasks, neuroimaging, microstructure, and functional connectivity of the hippocampus were measured before and after the trial. The study found that Resveratrol had a significant impact on subject’s ability to remember words. Subjects had a significant increase in functional connectivity in the hippocampus. And there was a decline in glycated hemoglobin (HbA1c), which indicates improved blood sugar control. The researchers concluded that Resveratrol can enhance memory along better hippocampus function.979 Resveratrol Improves Cerebral Circulation A study conducted at Northumbria University at Newcastle upon Tyne in the UK assessed the effects of Resveratrol on cognition and cerebral blood flow in healthy adults. In this double-blind, placebo-controlled study, 22 healthy adults received a placebo and 2 doses (250 and 500 mg) of trans-Resveratrol in counterbalanced order on separate days. The subjects performed a selection of cognitive tasks that activate the frontal cortex 45-minutes after taking Resveratrol. Near-infrared spectroscopy assessed frontal cortex changes in oxygenated and deoxygenated hemoglobin in order to evaluate blood flow and hemodynamics during the 36 minutes of task performance. The research team found that Resveratrol increased cerebral circulation. And this effect was entirely dependent on the size of the dose of Resveratrol. Blood flow was determined by measuring total hemoglobin concentrations. The researchers concluded that Resveratrol can increase cerebral blood flow even with a single dose of the supplement.980 Dosage Notes Resveratrol is found in small quantities in red wine, and some plant foods. Red wine contains about 1.5 – 3 mg of Resveratrol per liter of wine. So if you do the math, comparable amounts of Resveratrol from red wine for a 150 lb. person means 750 – 1,500 bottles of red wine a day. Resveratrol has a considerably shorter half-life than its cousin Pterostilbene. And is easily absorbed but

has poor bioavailability once digested.981 It’s half-life is 1 – 3 hours, and 2 – 5 hours following repeated dosing.982 Micronized Resveratrol, which has a much smaller particulate size, has been shown to have a 3.6-fold increase in bioavailability compared to standard Resveratrol.983 And many of the clinical studies done in animals suggest a human equivalent of 1 -2 grams for a 150 – 200 lb. person. Many supplement makers offer much smaller quantities in capsules or tablets. (I do not advise taking such high doses of Resveratrol). But even in small amounts, Resveratrol is believed to provide some of the benefits talked about in this chapter. Based on all of the published studies, the recommended daily dose of Resveratrol is 20 mg for heart health, insulin sensitivity and longevity. For cognitive benefit, and increasing cerebral blood flow, recommended dose is 250 – 500 mg of Resveratrol. It’s better to dose on the lower end of recommended doses of Resveratrol. And see how your body reacts. Side Effects Resveratrol is non-toxic and supplementation is well-tolerated by most people. We do not have many human studies on Resveratrol and must rely on user reviews. Resveratrol has mild estrogenic activity in the body. So if you’re estrogen is low you should avoid supplementing with Resveratrol. This is a potentially serious side effect. And short of getting your labs done, it may show up as joint pain or arthritis-like symptoms. Some neurohackers report having trouble sleeping or staying asleep. Particularly if taken in the afternoon or evening. If you are dealing with a blood disorder which causes bleeding, you should avoid Resveratrol. If you are taking aspirin, warfarin or clopidogrel you should not use Resveratrol. Long term side effects reported by some neurohackers include diarrhea, discolored urine, dizziness, insomnia, jitters, joint pain, stomach pain and tendinitis. Available Forms Resveratrol comes in tablet, capsule or powder form and is available by several well-known supplement makers. Most Resveratrol supplements are made from Japanese Knotweed. And some from grape skin extract. The bioactive form used in clinical studies and found in supplements is ‘Trans-Resveratrol’. ‘CisResveratrol’ is a cis isomer and still bioactive but has a very different chemical structure. Purity of Resveratrol is extremely important. Most Resveratrol is made from Japanese Knotweed. A

poor-quality extract can contain high amounts of Emodin which can act as a laxative and cause stomach cramps. High purity Resveratrol extract (99%+) from Japanese Knotweed contains insignificant amounts of Emodin. And should cause far fewer side effects. Your safest bet when choosing a Resveratrol supplement is an extract from grapes or red wine which contain no impurities. Nootropics Expert® Recommendation Resveratrol 20 - 250 mg per pay I recommend using Resveratrol as a nootropic supplement. Your body does not make Resveratrol on its own. You can get some Resveratrol from red wine and a few other fruits. But studies have shown we may not get an adequate supply of Resveratrol from food sources in our diet. Especially if you don’t eat a lot of fruit containing Resveratrol every day. Or don’t drink red wine. I recommend choosing a Resveratrol supplement that is 99% pure from Japanese Knotweed. Or a pure extract from grapes or red wine. Resveratrol is unique among antioxidants because it easily crosses the blood-brain barrier. And helps protect your brain from free radical damage. Resveratrol helps improve memory by influencing the cAMP-dependent pathways in your brain that activate AMPK. And Resveratrol boosts cerebral blood flow which increases the amount of oxygen and nutrients your brain cells need for optimized cognition. Resveratrol is especially helpful for those concerned about developing Alzheimer’s or dementia. Because it helps prevent the accumulation of abnormal proteins like amyloid-beta. I suggest starting with a dose of at least 20 mg daily. And Resveratrol is a great compliment to a stack including any nootropic. One study showed Resveratrol worked synergistically with ALCAR to boost memory. And Resveratrol works particularly well when combined with Pterostilbene.

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Rhodiola Rosea Rhodiola Rosea is known for improving alertness, energy, memory and mood, is anti-anxiety and antidepressant, reduces fatigue, and boosts cognition and concentration Rhodiola Rosea L. (Golden Root, Roseroot) has been used for several thousand years in traditional medicine. It grows in primarily dry sandy ground at high altitudes in the arctic areas of Europe and Asia. The plant is 12 – 30 high and produces yellow blossoms. The Greek physician, Dioscorides, first recorded the medicinal applications of ‘rodia riza’ in 77 C.E. in De Materia Medica.984 In Russia, Rhodiola Rosea is widely used as a remedy for fatigue, poor concentration, and decreased memory. It’s also believed to make workers more productive. The Journal of the American Botanical Council reported on 180 studies done on Rhodiola Rosea since 1960. The bulk of the research shows how this herb works in treating physical endurance, fatigue, depression, impotence, infections, fertility, cold and flu, tuberculosis, cancer, and anxiety.985 German researchers describe the benefits of Rhodiola Rosea for pain, headache, scurvy, hemorrhoids, as a stimulant, and as an anti-inflammatory.986 This ancient remedy has remarkable stress-relieving and anti-anxiety properties. And stands shoulder to shoulder with some of the most potent drugs used to treat depression and anxiety. This ancient herbal adaptogen has remarkable anti-depressant and anti-anxiety qualities. And has been shown to be as good as many prescription pharmaceuticals in treating depression and anxiety. In total, Rhodiola Rosea contains 140 compounds in the roots and rhizome. The critical components include rosavin, rosarian, and rosin, collectively known as rosavins. Certain chemicals must be present for Rhodiola Rosea to work. And these include rosavin, rosarin, rosin, salidroside, and tyrosol. The first 3 of these compounds are found only in Rhodiola Rosea. It takes a synergistic combination of these chemicals for this herb to be effective. To ensure the supplement you choose works and contains pure Rhodiola Rosea, it needs to be standardized to contain at least 3% rosavins and 1% salidroside. This is the ratio found in the natural root. (See more about selecting the right Rhodiola Rosea supplement in “Available Forms” later in this chapter). Studies on organs, tissues, cells, and enzymes show that Rhodiola Rosea extracts exhibit adaptogenic effects that are neuroprotective, cardio protective, anti-fatigue, anti-depressive, anxiolytic, nootropic, and has life-extension qualities.987 Rhodiola Rosea is known as an adaptogen. Which means it helps your body adapt to stress, both mental and physical.

How does Rhodiola Rosea work in the Brain? Rhodiola Rosea boosts brain health and function in several ways. But two in particular stand out. 1. Rhodiola Rosea enhances mood. Reports from the nootropics community, and data from clinical trials show that Rhodiola Rosea encourages a balanced mood. One double-blind, placebo-controlled trial worked with male and female subjects aged 18 – 70 years. All were diagnosed with mild to moderate depression. One group received two 340 mg tablets of Rhodiola Rosea extract (SHR-5) daily. A second group received double the dose of the first group per day. And the third group received a placebo daily. The efficacy of SHR-5 extract for depression complaints was assessed on the first day. And again on day 42 of the trial. The research team reported that Groups A and B saw significant improvements in depression, insomnia, emotions and overall quality of life. The team concluded that Rhodiola Rosea extract has potent anti-depressant qualities in those with mild to moderate depression. When administered in doses of either 340 or 680 mg per day over 6weeks.988 2. Rhodiola Rosea improves mental performance under stress. Mental fatigue can cause brain fog, and make it hard to focus. It can affect your performance at school, and on the job. Rhodiola Rosea stimulates your nervous system to fight fatigue that stifles mental clarity. And studies show it even saves injured neurons. And encourages the growth and development of brain cells. One animal study in China explored the effects of Rhodiola Rosea on the number of neurons in the hippocampus of rats with depression induced by chronic stress. This study has a direct correlation on how Rhodiola Rosea works in the human brain. And its value as a nootropic. In this study, 50 rats were divided into 5 groups: normal control, untreated, negative control, positive control and Rhodiola Rosea-treated groups. The research team found that the number of neurons in the hippocampus in the Rhodiola Roseatreated group were increased and recovered to normal level. The study concluded that Rhodiola Rosea promotes the proliferation and differentiation of neural stem cells in the hippocampus. And may play a role in saving injured neurons of the hippocampus.989 How things go bad Chronic stress and cortisol can damage your brain. Neuroscientists at the University of California, Berkeley, found that chronic stress triggers long-term changes in brain structure and function.990 Chronic stress changes neural networks. Cortisol creates a domino effect that hard-wires pathways between the hippocampus and amygdala. (The amygdala (lizard brain) is the area responsible for your fight-or-flight response).

This hard wiring caused by stress is not the way the brain was designed. But chronic, ongoing stress tricks the brain into rebuilding circuits and hunkering down for the long haul. This re-wiring appears to be permanent. Unless you intervene with something like Rhodiola Rosea. Chronic stress seems to ‘flip a switch’ in stem cells in the brain. And turns them into a type of cell that prevents connections to the prefrontal cortex. Preventing improved learning and memory. And laying down the scaffolding linked to anxiety, depression and PTSD (Post Traumatic Stress Disorder). ↓ Chronic stress reduces levels of serotonin and norepinephrine ↓ Chronic stress reduces the number of neurons ↑ Anxiety and depression increases ↓ Chronic stress induces brain fog and memory loss Under conditions of chronic stress and excess cortisol you experience mental and physical fatigue. Rhodiola Rosea benefits Rhodiola Rosea undoes damage to your brain caused by chronic stress. It helps keep it healthy. And even improves your body and brain’s response to stress. Rhodiola Rosea relieves stress by balancing your body’s stress-response system. And helps your body return to a relaxed state by influencing key brain chemicals like serotonin, norepinephrine and betaendorphins (opioid neuropeptides).991 Rhodiola Rosea can also help prevent and repair damage caused by C-reactive protein and free radicals. Rhodiola Rosea even provides protection and regeneration of neurons during periods of stress. It helps in the synthesis and re-synthesis of ATP. The main fuel source for the mitochondria in your cells. Any kind of fatigue you experience – regardless of source – Rhodiola Rosea is like your “magic bullet”. Mood, energy, stamina and concentration can all increase with a dose of this herb. Many neurohackers even report improved libido and sexual performance when using Rhodiola Rosea. If you get an effective dose of real standardized Rhodiola Rosea extract, you should experience an effect. How does Rhodiola Rosea feel? The time required to begin feeling the effects of Rhodiola Rosea depends on your genetics, mental and physical condition, environment, behavior and lifestyle. Some neurohackers report feeling its effects in just a few days. While others require as much as 3 weeks. Clinical studies show that most people experience the full benefits of Rhodiola Rosea in 30 – 40

days. If you don’t notice a change within 40 days, Rhodiola Rosea may not be effective for you. Many report that Rhodiola Rosea provides a pronounced anti-anxiety effect. Depression lifts and overall quality of life improves. Rhodiola Rosea should give you an energy lift. It could improve your mood, focus, level of concentration and alertness. The Research Rhodiola Rosea has a reputation in the nootropic community for its energizing and anti-fatigue qualities. One double-blind, placebo-controlled trial was carried out with 161 cadets aged from 19 – 21 years. The intent was to measure the effect of a single dose of Rhodiola Rosea extract (SHR-5) on capacity for mental work against a background of fatigue and stress. An additional objective was to try two different doses of the extract. The other dose being 50% higher. So the cadets were given either 2 or 3 capsules of Rhodiola Rosea extract. The study showed a “pronounced anti-fatigue effect” in the cadets. With no significant differences between the two dosage groups. But there was a “possible trend in favor of the lower dose” in the cognitive tests.992 Rhodiola Rosea as a nootropic The aim of this study was to investigate the effect of repeated low-dose treatment of Rhodiola Rosea extract (SHR-5) on mental performance with fatigued physicians. The researchers recruited a group of 56 healthy, young physicians working night duty at the Armenian State Medical University. Tests involved overall level of mental fatigue, associative thinking, short-term memory, calculation, ability of concentration, and speed of audio-visual perception. Tests were done before and after night duty during 3 periods of 2 weeks each. The young doctors received Rhodiola Rosea extract tablets or a placebo for the first 2 weeks. Followed by a 2 week ‘washout’ period. And finishing with another 2 weeks of Rhodiola Rosea extract tablets or a placebo. The research team found a statistically significant improvement in cognitive tests during the first 2 weeks. No side effects were reported. And the young doctors had a reduction in general fatigue under stressful conditions.993 Rhodiola Rosea as an anti-depressant One study published in Phytomedicine was run as a “proof of concept” trial to evaluate the efficacy of using Rhodiola Rosea compared to the anti-depressant ‘sertraline’ for major depressive disorder. Sertraline (Zoloft®) is a pharmaceutical SSRI used to treat depression, anxiety, panic attacks, and

obsessive-compulsive disorder (OCD). And it comes with a host of side effects including fatigue, diarrhea, anorexia, convulsions, confusion, decreased libido, and ejaculation failure. This trial recruited 57 people diagnosed with depression. They were given standardized Rhodiola Rosea extract, sertraline, or a placebo for 12 weeks. 3 different depression scoring tests were used during the trial. The researchers concluded that Rhodiola Rosea produced less antidepressant effect than sertraline, but it also resulted in “significantly fewer adverse events and was better tolerated.” The research team concluded that even though Rhodiola offered slightly less anti-depressant benefits, it possessed “a more favorable risk to benefit ratio for those with mild to moderate depression”.994 Dosage Notes Recommended dose of Rhodiola Rosea is 150 – 200 mg per day. Look for an extract that is standardized to contain rosavins and salidrosides in a 3:1 ratio. This mimics the ratio of these compounds that naturally occur in Rhodiola Rosea root. No additional benefit seems to come from taking more than 1,000 mg per day. Side Effects Rhodiola Rosea is a natural adaptogen and herb that has been used successfully for thousands of years. It’s considered non-toxic and safe. And very few side effects have been reported. Considerably higher than recommended doses could result in dry mouth, nausea, upset stomach, headache, insomnia and weight loss. Since Rhodiola Rosea acts as a Monoamine Oxidase Inhibitor (MAOI), you should not use it if you’re taking MAOI meds. MAOI’s are a type of anti-depressant drug used to treat bipolar disorder, panic disorder, social anxiety disorder and PTSD. MAOI meds influence serotonin levels in the brain. So taking MAOI’s in combination with Rhodiola Rosea has the potential to cause serotonin syndrome. Available Forms Rhodiola Rosea is available as a powder, capsules, tablets, and tea. Active ingredients of Rhodiola Rosea include rosavins and salidrosides. Make sure you look for the percentage of active ingredients listed on the bottle or package. Ideally, you’re looking for a 3:1 ratio of rosavins and salidrosides. This mimics the ratio of these compounds naturally occurring in the Rhodiola Rosea root. Now this is where it gets tricky. And probably the reason why some forum threads and user reviews report no effect from using Rhodiola Rosea.

In the late 1980’s, demand for Rhodiola Rosea-based phytomedicines dramatically increased. The wildgrown, raw material was over-harvested, resulting in a steady decline in the quality and effectiveness of Rhodiola Rosea. Studies revealed that other species of genus Rhodiola were being substituted for Rhodiola Rosea. While some of these mixed batches were highly variable in quality, others had no pharmacological or nootropic effect.995 So do your best to find out where the supplement maker gets their raw Rhodiola Rosea. Hostile environments like Siberia seem to produce higher quality Rhodiola Rosea. The active ingredients for most nootropic benefit include Rosavin, Rosaridin, Rosarin, Rosin, Salidroside, and Tyrosol. The first 3 are collectively referred to as “rosavins”. And the other big one is “salidroside” which has several iterations. Avoid supplements that list “other ingredients” on the label. And look for Certified Organic to ensure the root used to make your Rhodiola Rosea supplement is free of heavy metals, pesticides and herbicides. Nootropics Expert® Recommendation Rhodiola Rosea Extract 150 – 200 mg per day I recommend using Rhodiola Rosea as a nootropic supplement. Your body does not make Rhodiola Rosea on its own. So to get its benefits you must take it as a supplement. Rhodiola Rosea is especially helpful for those suffering from anxiety and stress. Studies show it helps stop and reverse the devastating effects of stress in your brain, and body. This nootropic helps repair the damage to neurons caused by chronic stress. Rhodiola Rosea is a powerful adaptogen. Which means it helps increase the effect of certain hormones when activity is low. And will block excess stimulation when activity is too high. Rhodiola Rosea as an adaptogen helps balance norepinephrine in the body caused by chronic stress. It also boosts serotonin and the feel-good opioid chemical beta-endorphins. Using Rhodiola Rosea can help eliminate brain fog, increase concentration during brutal periods like exams or business presentations, boost energy by increasing the ATP fueling your mitochondria, and protect your brain cells from free radical damage. Rhodiola Rosea helps alleviate mental and physical fatigue, improves stress response, and provides better quality of sleep. It can even help out your sex life. Rhodiola Rosea is especially helpful for those suffering from anxiety and panic disorders. Studies have shown the calming effect of this herb was equal to some popular antidepressant and anti-anxiety drugs. Without the side effects.

You can safely take up to 600 mg of Rhodiola Rosea extract daily if needed. Most get all the benefit they need with 150 - 200 mg. Half of the dose in the morning, and another early afternoon. And make sure your getting genuine Rhodiola Rosea extract with a 3:1 ratio of rosavins and salidrosides. Read the user reviews and labels.

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Rosemary Rosemary is known for boosting alertness, memory, mood, reducing anxiety, reducing inflammation, and may be effective for reducing the symptoms of Alzheimer’s Rosemary (Rosmarinus officinalis) is an evergreen herb belonging to the mint family Lamiaceae which is native to northern Asia and the Mediterranean. And is used world-wide as a culinary spice and medicine. Rosemary’s medicinal use dates back to the ancient Greeks and Romans in 500 B.C. Greek students wore garlands of Rosemary on their head to help stimulate memory during exams. Its genus name, Rosmarinus, is derived from the Latin word for ‘dew’ (ros), and ‘belonging in the sea’ (marinus). Legend says the Virgin Mary took shelter next to a Rosemary bush as she fled from Egypt. She threw her blue cape on a Rosemary bush, and the white flowers turned blue. This is how Rosemary or ‘rose of Mary’ got its name.996 Rosemary with its pleasant flavor and aroma, and bitter taste is used in many traditional dishes. Rosemary can be used in the form of fresh leaves, powder, or as an essential oil. Rosemary has also been used traditionally to relieve pain, improve memory, increase immunity, and promote hair growth. Rosemary is an excellent source of calcium, iron, and Vitamin A, Vitamin B6, and Vitamin C. And provides potent antifungal and antibacterial properties.997 Compounds found in Rosemary oil have been shown to increase memory. The compound 1,8-cineole acts as an acetylcholinesterase inhibitor which boosts acetylcholine levels in your brain. In the same way as drugs prescribed to treat dementia.998 A study conducted at Mahidol University in Thailand in 2013 tested Rosemary essential oil and its effects on the human central nervous system. 20 healthy subjects ages 18 – 28 years were asked to inhale the aroma of Rosemary essential oil. An EEG found that alpha brain waves decreased, and beta brain waves increased after inhalation of the oil. This change in brain wave activity boosted alertness and improved thinking performance. The study confirmed the stimulant effects of inhaling the aroma of Rosemary essential oil.999 Rosemary essential oil is also a proven stress-reliever. It acts by lowering cortisol levels. Research shows that Rosemary has stimulatory effects on brain wave activity, autonomic nervous system activity, and mood. How does Rosemary work in the brain?

Rosemary boosts brain health and function in several ways. But two in particular stand out. 1. Rosemary improves memory – Rosemary has traditionally been used to improve cognitive performance and mood. And these reports have been verified in recent clinical studies. A study conducted at the University of Northumbria in the UK worked with 144 volunteers. In this study, the group who inhaled Rosemary essential oil demonstrated an overall improvement in memory and mood.1000 In 2013, Jemma McCready and Dr Mark Moss from the University of Northumbria conducted a study with 66 adults. The focus of this trial was on prospective memory, which involved remembering things that were bound to happen in the future, or simply remembering things that were critical for everyday functioning. The test group were put into a room infused with Rosemary essential oil, and the control group in a room with no scent. The study found that the group in the Rosemary scented room performed 60-75% better on the prospective memory tasks than the control group.1001 In 2017, the same researchers presented their findings to the British Psychological Society Annual Conference in Brighton. In a follow-up study, they recruited 40 children age 10 – 11 to find out if Rosemary produced a similar benefit in the young. Once again, the test group were put into a Rosemary oil infused room, and the control group in a room with no scent. The researchers found that children in the Rosemary scented room performed 5 to 7% better in working memory scores than the kids in the control group.1002 2. Rosemary is neuroprotective – Rosemary’s bioactive compounds including phenolic diterpenes and triterpene acids are known to be potent neuroprotectors. Animal research demonstrates the phenolic compounds in Rosemary reduce oxidative stress. Animals pre-treated with Rosemary experienced far less brain damage during an ischemic stroke. And recovered with higher neurological scores because of an intact blood-brain barrier.1003 Rosemary extract has been used traditionally and in modern times to relieve pain. Studies show that terpenoids, and to a lesser extent rosmarinic acid significantly reduce pain sensitivity. Rosemary protects nerve fibers and prevents reduction in both myelin thickness and axon diameter. And helps maintain the plasticity of glial cells and astrocytes involved in pain maintenance. In turn preventing feelings of pain and alterations of the nervous system induced by nerve injury.1004 Its anti-neuropathic properties can be attributed to rosemary binding to nicotinic acetylcholine receptors which are polypeptides that respond to the neurotransmitter acetylcholine. When rosemary binds to

these receptors it reduces neuropathic hypersensitivity and protects nerve tissue.1005 How things go bad As we get older, our brain chemistry and energy metabolism changes. ↓ Concentration, attention, and mental agility decline ↓ Brain cell membranes degenerate ↓ Acetylcholine levels decline ↓ Free radicals and oxidative stress damage brain cells All of these age-related changes are contributing factors to the neurodegenerative diseases of aging, including Alzheimer’s and dementia. But even if you’re not concerned with the effects of aging, Rosemary can help. Rosemary benefits Rosemary has been used for millennia to protect and support brain function. Rosemary is a potent anti-inflammatory and antioxidant. Rosemary can boost concentration and memory. Simply smelling Rosemary can help you remember things better. 20 healthy volunteers performed subtraction and visual processing tasks in a cubicle diffused with the aroma of Rosemary. Mood was assessed before and after the test. And blood samples were taken during the study. The study showed improved performance and concentration related to how much 1,8-cineole was absorbed following exposure to Rosemary aroma. Speed and accuracy improved and there was a significant reduction in feelings of contentment as blood levels of 1,8-cineole declined.1006 Reductions in acetylcholine is implicated in neurodegenerative diseases such as Alzheimer’s and dementia. Rosemary inhibits acetylcholinesterase activity which increases acetylcholine levels in the brain. Amyloid-β proteins clump to form amyloid plaques and neurofibrillary tangles (NFT) causing memory loss in Alzheimer’s and dementia. The carnosic acid in Rosemary has been shown to suppress the formation of amyloid-β plaques.1007 Additional nootropic benefits from consuming or inhaling Rosemary, include enhanced cognitive performance, elevated alertness, and less anxiety.1008 How does Rosemary feel?

Many users of Rosemary report more energy and better clarity when thinking after taking the supplement. When used as a nootropic, Rosemary works as a cognitive stimulant and helps improve memory, alertness, and focus. People who use Rosemary essential oil report improved mood, lower stress levels, and fewer episodes of cortisol imbalance. Some report better immunity and blood circulation after supplementing with Rosemary. Likely due to its rich antioxidant and anti-inflammatory properties. Some neurohackers also like to include Rosemary in their diets as an herbal tea, or as a seasoning agent in food. It has a lovely flavour and aroma that can energize you instantly. Rosemary Clinical Research Rosemary boosts cognitive performance Researchers at Northumbria University, Newcastle upon Tyne wanted to find out how the aroma of essential oils affected human behavior. In this study, 20 healthy volunteers performed serial subtraction and visual information processing tasks in a cubicle infused with 4 drops of Rosemary essential oil. Mood was assessed pre- and post-testing, and blood samples were drawn at the end of the session. The study authors discovered that performance on cognitive tasks were related to the concentration of 1,8-cineole from Rosemary absorbed in blood from simple exposure to Rosemary aroma. Performance improved as concentrations of 1,8-cineole increased. This performance boost was reflected in speed and accuracy. Mood changes were not as significant. But the researchers did notice that feelings of contentment declined as 1,8-cineole levels in blood decreased. The researchers concluded that compounds absorbed from Rosemary aroma had a positive effect on cognition and mood.1009 Rosemary increases alertness A study at the University of Miami School of Medicine recruited 40 adults to observe the effects of aromatherapy on alertness and mood. Participants were exposed to the aromas of Lavender (considered a relaxing odor) or Rosemary (considered a stimulatory odor) for 3 minutes each. Participants were also given simple math computations before and after the therapy. A study at the University of Miami School of Medicine recruited 40 adults to observe the effects of

aromatherapy on alertness and mood. Participants were exposed to the aromas of Lavender (considered a relaxing odor) or Rosemary (considered a stimulatory odor) for 3 minutes each. Participants were also given simple math computations before and after the therapy. The Lavender group showed increased beta power suggesting increased drowsiness, and less depression. The adults in this group also reported feeling more relaxed and performed the math computations faster and more accurately following aromatherapy. The Rosemary group on the other hand showed decreased frontal alpha and beta power suggesting increased alertness. The Rosemary group on the other hand showed decreased frontal alpha and beta power suggesting increased alertness. The Rosemary adults also had lower anxiety scores. They reported feeling more relaxed and alert. They were faster doing math computations but unlike the Lavender group were not more accurate.1010 Rosemary Recommended Dosage The recommended dosage of Rosemary leaf for nootropic benefit is 750 mg per day. Rosemary extract (standardized to 20% rosmarinic acid, 20% diterpenes, and 9% carnosic acid) is 275 mg per day. Rosemary essential oil in a diffuser 1 mL (10 – 40 drops) as needed. Rosemary Side Effects Rosemary as a nootropic is considered non-toxic and safe when used as recommended. Rosemary as been used by humanity for millennia as a food condiment. So as a nootropic should be well tolerated by most people. Rosemary has been shown in animal models to reduce sperm count in male rats, and abort fetuses in female rats. But keep in mind that the dosage size of Rosemary in rats was 250 and 500 mg/kg of body weight. Much higher doses than we would use as a nootropic. Authors of this study attributed these side effects to reductions in testosterone caused by high-dose Rosemary.1011 Do no use Rosemary if you are using blood-thinning medication. Or ACE inhibitors used to treat high blood pressure. Do NOT take Rosemary essential oil internally because it could cause vomiting, uterine bleeding, kidney irritation, increased sun sensitivity, skin redness, and allergic reactions.

Do not use Rosemary as a nootropic supplement if you are pregnant because it may cause a miscarriage. And if you’re breastfeeding you should use Rosemary in moderation. If you are diabetic, pre-diabetic or suffer from insulin resistance you should avoid using Rosemary as a nootropic.1012 Avoid using Rosemary if you are undergoing chemotherapy. Type of Rosemary to Buy Rosemary is available as a nootropic supplement in capsules, tablets, and as bags of powder. As an extract, look for Rosemary standardized to 20% rosmarinic acid, 20% diterpenes, and 10% carnosic acid. Rosemary essential oil can be used in aromatherapy or for topical application on your skin. Nootropics Expert® Recommendation Rosemary extract up to 750 mg per day. I recommend using Rosemary extract as a nootropic supplement. Either in capsule form or as aromatherapy. Your body does not make Rosemary on its own. So, to get its benefits you must take it as a supplement or use it in aromatherapy. Rosemary as a nootropic can be taken as a supplement in capsules or powder or steeped as Rosemary tea 2 or 3-times a day. Rosemary seems to be especially helpful for those dealing with Alzheimer’s and other neurodegenerative diseases. Rosemary increases acetylcholine, inhibits Amyloid-β plaques and tau tangles, reduces inflammation and eliminates heavy metals. Rosemary has been shown to help reduce anxiety and improve mood. And works quickly when used as an essential oil in aromatherapy. Simply the scent of Rosemary has been proven to boost alertness and memory. Purity and dosing are important when selecting a Rosemary extract supplement or essential oil. Choose a product where the manufacturer can verify their production and testing methods. And user reviews can be very helpful for choosing the best vendor and brand of Rosemary.

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Saffron Saffron is used for depression, PMS symptoms, post-partum depression, memory, appetite suppression, energy & stamina in athletes, and preventing neurodegenerative diseases like Parkinson’s and Alzheimer’s Saffron (Crocus sativus) as a nootropic is the dried crimson stigma of the C. sativus flower cultivated primarily in Iran. And is the world’s most expensive culinary spice largely due to the way it must be grown and harvested (by hand). The earliest reference to Saffron goes back to around 2,300 BC from Sargon, founder of the Akkadian empire. Sargon was born in a village on the shores of the Euphrates called Azupiranu (city of Saffron).1013 Since then, documentation of Saffron use over the last 4,000 years for at least 90 illnesses has been uncovered. Saffron takes a long time to germinate from seed and 3 years for the plant to flower. Once it blooms in mid-Autumn, the flowers must be picked carefully by hand within 1 – 2 weeks. Each Crocus sativus plant produces 3 – 4 flowers per season. Each flower produces a 3-pronged style, each prong terminating in a vivid crimson stigma. Saffron is the dried stigma of Crocus sativus. This labor-intensive production method makes Saffron the most expensive culinary spice in the world. Saffron contains the metabolites crocin, picrocrocin, safranal, and the antioxidants lycopene and zeaxanthin as well as Vitamin B12 all which provide its medicinal value.1014 As a nootropic, Saffron may be used for depression, PMS symptoms, post-partum depression, memory, appetite suppression, and preventing neurodegenerative diseases like Parkinson’s and Alzheimer’s. How does Saffron work in the brain? Saffron boosts brain health and function in several ways. But two in particular stand out. 1. Saffron boosts mood. Recent studies suggest that brain-derived neurotrophic factor (BDNF), Nerve Growth Factor, and cAMP Response Binding Protein (CREB) all play a role in anxiety and depression. Further research shows that Saffron has a significant effect on BDNF, NFG and cAMP levels in the brain.1015 Which likely explains why Saffron is so effective in treating teenage anxiety and depression. One study in 2018 had 80 participants aged 12 – 16 years with anxiety and depression try Saffron extract (Affron®) 14 mg or a placebo for 8 weeks. The study concluded that Saffron extract was effective in relieving the symptoms of separation anxiety, social phobia and depression compared to placebo.1016

Researchers in the psychology department at Murdoch University in Perth conducted a systematic analysis of every clinical trial they could find for high-quality, randomized, double-blind studies using Saffron, a placebo and antidepressant meds as controls in humans (not animals). The team concluded that clinical trials support the use of Saffron for the treatment of mild to moderate depression.1017 2. Saffron for preventing Alzheimer’s. One of the most common symptoms in Alzheimer’s patients is depression. And doctors commonly prescribe antidepressants for treatment. Including drugs like sertraline (Zoloft®).1018 Despite the fact that these meds don’t work for Alzheimer’s disease and come with a host of side effects.1019 An alternative treatment is obviously needed. So researchers set up a double-blind, placebo-controlled trial with 46 Alzheimer’s patients. The patients were given 15 mg of Saffron twice daily or placebo for 16 weeks. The results of this trial showed Saffron produced a significantly better reduction in behavioral and psychological symptoms than placebo. And concluded, “Saffron is both safe and effective in mild to moderate Alzheimer’s”.1020 The acetylcholinesterase inhibitor donepezil (Aricept®) is also prescribed to Alzheimer’s patients. For increasing acetylcholine which has been found to be low in these patients. A 22-week, randomized, double-blind trial with 54 Alzheimer’s patients was conducted to compare donepezil with Saffron. Patients received either 15 mg of Saffron twice per day or 5 mg of donepezil twice per day for the extent of the trial. This phase II study found Saffron extract was as effective as donepezil in the treatment of mild to moderate Alzheimer’s. But Saffron did not produce the side effect of vomiting.1021 How things go bad Depression is a growing health problem. With over 10% of Americans taking prescription antidepressants. Of whom 90% experience at least one adverse effect. Ranging from sexual dysfunction to convulsion to bleeding disorders. Antidepressant use can result in: ↓ Abnormal bleeding ↓ Agitation, aggression, anxiety, and delirium ↓ Confusion, convulsions and even death ↓ Decreasing memory, delusional thinking ↓ Hallucinations, headaches, and heart attacks

↓ Insomnia, lethargy, nightmares, and panic attacks ↓ Sedation, impaired driving, slow speech ↓ Sexual dysfunction, priapism ↓ Panic attacks, paranoia, suicidal thoughts, violent behavior ↓ Serotonin Syndrome, withdrawal symptoms A growing database of studies and user reviews show that Saffron helps treat depression without the risky side effects of prescription antidepressants. Saffron has also been shown to be effective with other conditions for which antidepressants are prescribed. Including anxiety, Alzheimer’s, and obsessive-compulsive disorder (OCD). We even have reports of Saffron reversing the sexual dysfunction caused by using prescription antidepressants. Saffron benefits To experience Saffron’s nootropic value you’ll need to use more than a sprinkling of the spice from your local supermarket. Studies show Saffron could be an alternative to some popular antidepressant meds.1022 And for anxiety.1023 Another study with 18 – 45-year-old women suffering from post-partum depression showed Saffron effective in reducing depression.1024 And a group of women aged 18 – 45 dealing with Premenstrual Syndrome (PMS) found that Saffron was effective in relieving depression during two menstrual cycles (cycles 3 and 4).1025 Saffron is a smooth muscle relaxant and helps lower blood pressure. Likely because of its inhibitory effect on histamine H1 receptors, stimulatory effect on ß2-adrenoceptors, and antagonist effect on muscarinic receptors.1026 Saffron inhibits acetylcholinesterase which increases acetylcholine in your brain. Improving brain signaling and helping learning and memory.1027 Saffron inhibits the deposition of amyloid β-peptide (Aβ) fibrils which has been implicated in Alzheimer’s.1028 Several human studies show Saffron as effective as some popular antidepressants in treating mild to moderate anxiety and depression.1029 Some of the symptoms of Parkinson’s Disease originate from under-utilization of dopamine in the substantia nigra area of the brain. Studies show Saffron helps protect the substantia nigra dopamine neurons associated with Parkinson’s.1030

Newly published studies show Saffron helps protect your eyes from ultraviolet blue light radiation (UVB). And flicker sensitivity from glaring monitors and headlights.1031 Saffron improves the oxygen and nutrient supply required for healthy eyes. By boosting blood flow in the retina and choroid of your eyes.1032 How does Saffron feel? Many neurohackers report supplementing with Saffron has helped them stop eating junk food, avoid nighttime snacking, and they’re no longer obsessed with thinking about food all the time. Saffron has been proven to help with Age-Related Macular Degeneration (AMD). Vision may be sharper. And you can see a line or two further down the Snellen chart at your next eye appointment. Glare from headlights during nighttime driving and flicker from monitors is no longer a problem. You may experience an improvement in mood when supplementing with Saffron. No longer overreacting, and work-related stress now feels like you are again in control. Many neurohackers report an increase in energy and better libido with Saffron. Feeling tired and emotional is a thing of the past. You’re back to your bright, positive, happy self! Saffron Clinical Research Clinical research into the efficacy of Saffron is encouraging. But trial lengths have typically been limited to 4 – 6 weeks. And sample sizes are relatively small (30 – 40 people). And keep in mind of the potential for bias because most clinical trials with humans have been conducted in Iran. Which produces nearly 90% of saffron for the world market. But these are still highquality studies. Saffron as good as Prozac A double-blind, randomized trial with 40 adult outpatients suffering from major depression was conducted at the University of Tehran. The study compared Saffron petals with fluoxetine (Prozac®) for the treatment of depression. Patients were given 15 mg of Saffron petals in the morning and evening, or 10 mg fluoxetine morning and evening for 8 weeks. The study concluded that Saffron petals were as effective as fluoxetine in the treatment of mild to moderate depression. The remission rate was 25% in both groups with no significant differences in side effects.1033 Saffron for Alzheimer’s Disease There is increasing evidence to suggest that Saffron could be used in the management of Alzheimer’s Disease.

In one Iranian study, 54 adults aged 55 year or older with Alzheimer’s participated in a 22-week, double-blind trial. Patients were randomly assigned 30 mg per day of Saffron (15 mg twice per day) or 10 mg per day of donepezil (Aricept®) (5 mg twice per day). The study found that Saffron was as effective as the drug donepezil in the treatment of mild to moderate Alzheimer’s after 22 weeks.1034 Other research shows that Saffron may inhibit the aggregation of amyloid-β in the human brain and may therefore be useful in Alzheimer’s.1035 46 patients with Alzheimer’s volunteered for a 16-week, double-blind trial. Patients were randomly assigned 15 mg of Saffron twice per day or a placebo for the 16-week study. After 16 weeks, Saffron produced a significantly better outcome on cognitive function than placebo. The study concluded, “This double-blind, placebo-controlled study suggests that at least in the shortterm, Saffron is both safe and effective in mild to moderate Alzheimer’s.”1036 Saffron for ADHD A randomized double-blind study was conducted with 54 children 6-17 years old who were diagnosed with ADHD. The children received 20 – 30 mg methylphenidate or 20 – 30 mg Saffron per day for 6 weeks. Symptoms were assessed using the Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6. The researchers found no significant difference in reduction of ADHD symptoms between the two groups. And concluded, “Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate.”1037 Saffron Recommended Dosage Recommended dose of Saffron is 25 – 30 mg twice per day for mild to moderate depression. Clinical studies have evaluated doses ranging from 20 – 400 mg per day of Saffron. Dosages up to 1.5 g per day of Saffron are thought to be safe.1038 With toxic effects reported for 5 g doses. As with many nootropics, more is NOT better when using Saffron. Some research shows that dosages above 1.5 g of Saffron can be extremely toxic. Saffron Side Effects Genuine Saffron is non-toxic and well-tolerated by most people when used at the recommended dosage. Some reported side effects of Saffron include headaches, nausea, dizziness, vomiting, and mania (esp. if

you are bipolar). Saffron can aggravate asthma symptoms. 5 g of Saffron are associated with toxic effects. And very high doses of Saffron (10 – 20 g) can be deadly. No drug interactions have been reported. But interactions with anti-aggregating drugs are theoretically possible. Do NOT use Saffron if you have a bleeding disorder. Type of Saffron to buy Saffron as a nootropic is typically sold in capsules. Most individual Saffron supplements on the market are standardized (for 0.3% safranal) usually with 88.5 mg ‘Saffron extract’. For nootropic use, look for supplements guaranteed to contain a patented version of Saffron extract. Otherwise, you’ll not likely experience the cognitive benefits of this nootropic for reasons I’ll go into in a minute. Affron®: Manufactured by PharmActive Biotech Products in Madrid, Spain and not easily found in Saffron products sold in the USA. Satiereal®: Made by PLT Health Solutions in Morristown, NJ and included in select Saffron products. Safranal®: Manufactured by Sigma-Aldrich and included in some Saffron supplements. Saffron is also included in much smaller amounts in some vison/eye formulas. While extremely effective for vision health, it’s not enough for much cognitive benefit. Keep in mind that Saffron is the most valuable medicinal food plant on the planet. Which makes it a primary target by unscrupulous marketers for adulteration. Common adulterants include mixing Saffron with things like beet, pomegranate fibers, and red-dyed silk fibers to decrease the cost of Saffron. Sometimes the flowers of other plants, including safflower, marigold, arnica and tinted grasses are fraudulently mixed with genuine Saffron stigmas. The common mislabeling of turmeric (curcuma longa) as “Indian saffron”, “American saffron”, or “Mexican saffron” can easily be mistaken as genuine Saffron. When Saffron is used for therapeutic purposes such as a nootropic supplement, adulteration will make it completely useless or even harmful.1039 Before you buy your Saffron supplement make sure you check that it’s a reputable supplement manufacturer who tests all their raw ingredients and encapsulated product. This is a classic case of discounted or cheap Saffron is not a bargain. But something else entirely. Buyer

beware! Nootropics Expert® Recommendation Saffron 25 – 30 mg twice a day I recommend using Saffron as a nootropic supplement. Your body does not make Saffron on its own. So to get its benefits you must take it as a supplement. Saffron is especially helpful for suffering from anxiety and depression. Studies show Saffron to be as effective as some popular antidepressants but without the side effects. If you are currently using antidepressants, Saffron may help alleviate the sexual dysfunction caused by these drugs. Saffron seems to be an effective way to control appetite. No snacking between meals and you’re no longer obsessed about food. Saffron has the added benefit of more energy and stamina to help you through your day. You can safely take up to 200 mg of Saffron daily if needed. But dosed 100 mg at a time. Be familiar with the associated side effects of higher doses of Saffron. For nootropic use, choose a patented form of Saffron supplement such as the ones I’ve described above under “Type of Saffron to Buy”. Saffron is also a very effective vision supplement. Driving at night is easier on your eyes. And the flicker caused by screens and monitors won’t leave you with eye fatigue later in the day. For nootropic benefit look for genuine, verified pure Saffron or Saffron extract (standardized to 0.3 or 0.1% safranal).

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SAM-e SAM-e has been shown to relieve depression, anxiety, brain fog, and pain including arthritic and fibromyalgia pain, improve memory, mood and sociability, and support liver health SAM-e (S-Adenosyl Methionine, Ademethionine, Adomet) is the naturally occurring amino acid methionine bound to an ATP molecule. And is found in nearly every cell in your body. SAM-e helps produce and breakdown the neurotransmitters acetylcholine, dopamine, serotonin, norepinephrine and melatonin in your brain. SAM-e maintains cell membranes and plays a role in a healthy immune system. Studies show that SAM-e is very effective in treating depression without the side effects of prescription antidepressants. And while pharmaceutical antidepressants can take from 6 to 8 weeks to begin working, SAM-e can work much faster. The latest research shows that SAM-e can be anti-anxiety, reduces pain including in fibromyalgia, and can improve learning, memory and mood. SAM-e is made from methionine and ATP (adenosine triphosphate) during a cycle that recycles the amino acid homocysteine. This cycle requires Vitamin B6 and B12 and folate (B9) to work properly. SAM-e is a precursor to the crucial antioxidant glutathione which is used in your brain and liver. When glutathione levels drop in your body, liver damage from oxidative stress begins within seconds of exposure to alcohol or toxins. SAM-e is a methyl donor that contributes to several essential processes in your brain. As a methyl donor, SAM-e is involved in the production and recycling of hormones, cytokines, and the neurotransmitters acetylcholine, dopamine, norepinephrine, and serotonin. This methyl donor process is call ‘methylation’ and contributes to gene expression. Affecting how your cells work and communicate including your cell DNA. SAM-e modifies important molecules in cell membranes that control communications within and between brain cells. SAM-e boosts the number of muscarinic receptors in certain parts of your brain which are critical to this cellular communications network. SAM-e is used to treat depression, anxiety, osteoarthritis pain, fibromyalgia, and liver disease. SAM-e is sold as an OTC supplement in the United States and Canada. And as a prescription drug in several European Union countries, and Russia. SAM-e is marketed under the brand names Adomet, Gumbaral, Samyr, Heptral, Agotan, Donamet, Isimet and Admethionine. How does SAM-e Work in the Brain? SAM-e boosts brain health and function in several ways. But two in particular stand out.

1. SAM-e helps alleviate depression. SAME-e is one of the main building blocks your brain needs to produce the neurotransmitters acetylcholine, dopamine, serotonin, norepinephrine and melatonin. By raising the levels of dopamine in your brain, SAM-e helps enhance memory, motivation and learning. Researchers at the West Los Angeles VA Medical Center studied the antidepressant effect of oral SAMe in a randomized, double-blind, placebo-controlled trial for 15 patients with major depression. The researchers found that SAM-e is a safe, effective antidepressant with few side effects and a rapid onset of action. And may be useful for those who cannot tolerate prescription tricyclic antidepressants.1040 2. SAM-e directly influences neuronal signaling. SAM-e increases the number of muscarinic receptors in the hippocampus. We have two kinds of acetylcholine (ACh) receptors in our brain. 1) Nicotinic receptors and 2) Muscarinic receptors. Most of the nootropics we investigate here in Head First influence nicotinic receptors and ACh. Muscarinic receptors have a very different mechanism of action. They are part of a large family of Gprotein-coupled receptors (GPCRs) which are used as an intracellular secondary messenger system. Your brain has a very complex system of control to regulate different processes going on in different cells at different times. For this to work, there must be a sophisticated means of communication between cells. GPCRs and their G proteins provide this intercellular communication. And form one of the most important signaling systems in your brain. They are involved in nearly every aspect of your physiology and behavior. G proteins work by binding neurotransmitters, hormones, growth factors, cytokines, odorants and photons at the cell surface to the GPCR, and activate that receptor. Everything you see, hear, smell, or taste goes through this signaling process. And SAM-e increases the number of these muscarinic receptors in parts of your brain, including your hippocampus. In one study, aged rats were given SAM-e for 30 days. Supplementation with SAM-e restored the number of muscarinic receptors to levels found in the same areas in young animals.1041 Supplementing with SAM-e to increase muscarinic receptors in your brain can boost neuroplasticity and increase learning, memory, mood and even smell and vision. How things go bad You have healthy levels of SAM-e throughout your body when you’re young. But as you age, your body makes less of it. This is why young people bounce back from difficult experiences more easily. They’ve got higher levels of dopamine and a higher pain threshold than adults. SAM-e is a major methyl donor in your body. It is involved in the biosynthesis of hormones, neurotransmitters, proteins and phospholipids.1042

SAM-e participates in a sequence of events involving folic acid (folate) and Vitamin B12. Folate converts to 5-MTHF (5-methyltetrahydrofolate) which converts freely circulating homocysteine back into the amino acid Methionine (using Vitamin B12). L-Methionine then binds to an Adenosine group from ATP to create SAM-e. SAM-e is then able to donate methyl groups (called methylation) to a variety of reactions including the production and breakdown of the neurotransmitters dopamine, serotonin, norepinephrine and melatonin in your brain. This methylation process degrades SAM-e into S-Adenosylhomocysteine. Which is then fed back into this cycle from the beginning. This process is referred to as a ‘one-carbon cycle’. If you don’t have enough folate or Vitamin B12 available, this SAM-e methylation process breaks down. And the result can be depression, brain fog, poor recall and memory, and pain. This lack of folate and Vitamin B12 can affect you regardless of age. This is a big enough problem that the Canadian government mandated folate fortification of all flour, and some corn and rice products to address this issue in 1998.1043 Low levels of SAM-e, folic acid, Vitamin B6 and B12 can lead to all kinds of problems. And genetic defects that don’t allow the use of these important vitamins can result in the same symptoms. ↓ Cognition, memory, recall, and mood diminish ↓ Folic acid, Vitamin B6 & B12 absorption declines ↑ Homocysteine levels rise ↑ Pain levels rise ↓ Mental health, language and fine motor skills decline All of these changes in brain energy metabolism are contributing factors to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, ALS, epilepsy, and dementia. But even if you’re not concerned with genetic defects, a lack of B-Vitamins, or the effects of aging, SAM-e can help. SAM-e benefits Stress-related disorders like anxiety, major depression and PTSD are some of the most debilitating illnesses known to man. And if you’re reading this, and dealing with any of these, supplementing with SAM-e may help. To cope with stress requires changes in the expression of “immediate-early genes” in your hippocampus. The same area of your brain you use for learning and memory. Stressful events result in epigenetic (gene) modifications within ‘immediate-early genes’ in your

hippocampus neurons. DNA methylation acts to suppress the expression of these genes. This is where SAM-e comes in… SAM-e is a methyl donor for the enzyme that methylates your DNA. When SAM-e levels are high enough, a stressful event will not result in DNA de-methylation. Instead, a stressful event enhances DNA methylation of ‘immediate-early genes’. Which suppress their expression and allows you to adapt in a healthy way to this stressful situation.1044 SAM-e is a powerful antidepressant. In 2005, researchers combed through the databases of Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register. And collated the findings of randomized, controlled trials studying SAM-e for depression through to September 2001. The team concluded after analyzing all the clinical evidence that SAM-e was effective in treating major depression in adults.1045 SAM-e is also a potent pain-killer. A recent study looked at 56 people with arthritis in their knees. One group took the COX-2 inhibitor Celebrex while the other took SAM-e for 16 weeks. Researchers found that SAM-e was as effective as Celebrex at eliminating pain. And without the potential side effects of heart attack or stroke that can be caused by using Celebrex.1046 Another study on the effect of SAM-e with 17 fibromyalgia patients confirmed a close relationship between primary fibromyalgia and psychologic problems including depression. SAM-e treatment improved the depressive state of these patients. And SAM-e was found to be an effective and safe therapy in the management of fibromyalgia.1047 How does SAM-e feel? For some, supplementing with SAM-e can be life-changing. SAM-e can have a profound effect on emotions, depression, and feelings of anxiety. You may experience improved concentration, energy, alertness, and feelings of well-being. Even vision can become clearer. Once you start supplementing with SAM-e, you should experience at the very least, a general sense of well-being. SAM-e works particularly well for those who deal with depression or anxiety. Neurohackers report that they no longer have panic attacks. And the feeling of doom is gone. Adding SAM-e to your nootropic stack can improve sociability, and not feeling overwhelmed by life. Brain fog lifts and thinking is clearer and faster. Others say that the “dark cloud has lifted”, and all the negativity and stress is gone. Things that normally would irritate are just brushed off, and you move on.

One big word of caution: SAM-e needs Vitamins B6 & B12 and folate to work. Or SAM-e will elevate your homocysteine levels. High homocysteine can cause heart attacks. You’ll notice reference to B-Vitamins several times in this chapter on SAM-e. It is that important. Use Vitamin B6 & B12 and folate every day that you supplement with SAM-e. Or use a B-Complex formula that contains folate (B9). The Research SAM-e Lifts Mood We have made significant progress in the last 100 years in diagnosing and treating depression. And yet, 10’s of millions still suffer from depression. In 2014, an estimated 15.7 million adults in the United States had at least one major depressive episode in the previous year.1048 In the United States, one in ten Americans are using antidepressants.1049 I don’t have statistics from other countries but I suspect many have similar problems. Unfortunately, antidepressants only work 30 – 50% of the time. And come with a host of side effects. One reason that many people continue to suffer from depression is that most doctors are not aware of the link between homocysteine and depression. If you’re dealing with depression and have had little success with antidepressants, you may have something as simple (and as serious) as a folate deficiency. Or low levels of Vitamin B12. Studies show a link between folate deficiency and impaired metabolism of serotonin, dopamine, and norepinephrine. One study looked at 46 patients with severe depression. 24 of these patients had raised levels of homocysteine. And significantly lower levels of folate, SAM-e, and other metabolites. The researchers concluded that looking at total homocysteine levels could be a measure of depression. Caused by folate deficiency, impaired methylation (SAM-e), and neurotransmitter metabolism (SAMe). And a potential benefit to simply using vitamin replacement to treat severe depression.1050 Or supplementing with SAM-e to treat depressive symptoms. SAM-e to Treat Adult ADHD Ritalin and Adderall are thought to be the most effective treatment in children and adults with ADHD. These stimulants work by potentiating both dopamine and norepinephrine at the synaptic cleft. But stimulant meds for ADHD come with side effects. SAM-e acts as a methyl donor and is involved in many metabolic pathways. It has both adrenergic and dopamine receptor agonist activity. A research team at the University of California used SAM-e with subjects diagnosed with Adult ADHD in a 9-week double-blind, placebo-controlled trial. The research team found that 75% of the patients had a significant improvement in ADHD symptoms

while using SAM-e. And the 25% who did not respond to SAM-e, did not respond to Ritalin either.1051 SAM-e Treats Depression Scientists at the US Department of Health and Human Services conducted an analysis of 102 individual studies in 25 databases on SAM-e and depression in 2002. The report distilled data gleaned from published studies conducted around the world up to 2002. This comprehensive report is called, ““S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease.” The researchers found that SAM-e is just as effective as standard antidepressant drugs at treating depression. The agency concluded, “Treatment with SAM-e was equivalent to standard therapy for depression”.1052 Dosage Notes Recommended dosage of SAM-e for nootropic benefit is 400 mg per day. SAM-e for depression: 400 – 1600 mg daily in divided doses SAM-e for bone and joint health: 200 – 1200 mg daily in divided doses SAM-e for liver problems: 1600 mg daily in divided doses Some research and many user reports suggest that once positive effects are achieved, SAM-e doses can be reduced. Some report benefit with as little as 100 mg of SAM-e daily. Studies show that SAM-e should be consumed with B-Vitamins. When SAM-e donates its methyl group, it breaks down into homocysteine. Elevated homocysteine levels are associated with increased heart disease, birth defects and depression. In order to prevent homocysteine accumulating, sufficient levels of B-Vitamins must be present to convert homocysteine into the potent antioxidant glutathione. Take SAM-e on an empty stomach and an hour before eating any food. SAM-e is best digested in your intestines and not your stomach. Not letting SAM-e settle into your digestive tract could cause stomach upset. Side Effects SAM-e is produced naturally in your body. So is considered well-tolerated and safe. If you have bipolar disorder, you could develop mania when supplementing with SAM-e. So check with your doctor before using SAM-e. If you’re on antidepressant medication, you should check with your doctor before supplementing with SAM-e. High doses of SAM-e can cause gas, upset stomach, diarrhea, constipation, dry mouth, headache, dizziness, anxiety or skin rashes. SAM-e may also trigger an allergic reaction in some people.

Available Forms SAM-e is available in 200 and 400 mg tablets. For optimal effects with SAM-e, stable, enteric-coated tablets are recommended. SAM-e should be taken on an empty stomach, either one hour before or two hours after meals. SAM-e is highly unstable so check expiration dates. And you should get tablets that are packed in sealed, gel-packs for freshness. Avoid SAM-e in powder form as you’ll likely be unsatisfied with the results. Nootropics Expert® Recommendation SAM-e 400 mg per day I recommend using SAM-e as a nootropic supplement. Your body does make some SAM-e on its own. But SAM-e levels decrease as we age. And you cannot get SAM-e from food. SAM-e is critical for the methylation process needed for making important neurotransmitters including acetylcholine, dopamine, serotonin, norepinephrine and melatonin. SAM-e is also involved in the cycle which produces the critical antioxidant glutathione. And it’s involved in maintaining brain cell membrane integrity and fluidity. SAM-e increases muscarinic receptors in your hippocampus which boosts the activity of acetylcholine and other critical neurotransmitters in your brain. Leading to improved learning, memory and mood. SAM-e is especially helpful if you’re dealing with depression. Or having difficulty coping with any kind of stress. I suggest a dose of 400 mg daily. It may take a while for SAM-e to build up in your system. So be patient. Once you’re achieving the affects you want from SAM-e, you can eventually try scaling back your dose to 100 or 200 mg.

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St. John’s wort St. John’s wort has been shown to relieve depression as well as some prescription antidepressants St. John’s wort (hypericum perforatum) is regarded as a wildflower, herb and weed. As a nootropic, St. John’s wort is considered a powerful antidepressant. St. John’s wort is native to Europe. But can be found growing wild throughout Asia, Africa, North and South America and Australia. Greek physicians Galen and Dioscorides prescribed St. John’s wort as a diuretic, for healing wounds and treating menstrual disorders. In the Middle Ages, it was used as a talisman for warding off evil spirits. St. John’s wort is best harvested on St. John’s Day (June 24) when the herb is in peak bloom. Legend has it that if you placed a sprig of the herb under your pillow on St. John’s Eve, St. John himself may appear in a dream, and bless you for another year. (Not sure if this applies when you put a bottle of St. John’s wort extract under your pillow, but worth a try). St. John’s wort first crossed the radar of modern herbalists and naturopaths in 1997. A study published in the British Medical Journal entitled, “St John’s wort for depression--an overview and meta-analysis of randomized clinical trials” pushed it to superstar herbal antidepressant status. This meta-analysis of 23 previously published studies on St. John’s wort was drawn from foreign medical journals. The analysis showed that overall, St. John’s wort was significantly superior to placebo. And was as effective as pharmaceutical antidepressants.1053 The British Medical Journal published another study in 2005 showing that St. John’s wort was equally effective in treating depression and better tolerated than the widely prescribed antidepressant paroxetine (Paxil).1054 The two major active constituents of St. John’s wort are hypericin (a naphthodianthrone) and hyperforin (a phloroglucinol). The plant contains a total of seven groups of medicinally active compounds.1055 Researchers have extensively documented St. John’s wort as having antidepressant, antiviral, antioxidant, anti-cancer, and antibacterial effects.1056 The most recent clinical studies show that hyperforin is the constituent in St. John’s wort that has the most antidepressant action. If you’ve had limited success using St. John’s wort for depression and anxiety, your choice of supplement may be the problem. Go to “Dosage Notes” in this chapter to learn what extracts work best. How does St. John’s wort Work in the Brain? St. John’s wort boosts brain health and function in several ways. But two in particular stand out.

1. St. John’s wort reduces depression. Hyperforin is the major antidepressive constituent of St. John’s wort. Hyperforin inhibits the uptake of serotonin, dopamine and norepinephrine in the brain.1057 By making more of each of these neurotransmitters available in the brain, mood is elevated and depressive symptoms decline. Clinical trials also demonstrate that the level of antidepressant effect of St. John’s wort extract is entirely dependent on the concentration of hyperforin.1058 A study in Berlin compared the efficacy of using St. John’s wort extract (WS 5570) to paroxetine (Paxil) in treating moderate to severe depression. In this multicenter, randomized, double-blind study, 130 patients who received 900 mg or 1800 mg per day of St. John’s wort, or 40 mg of paroxetine were included. The study showed that St. John’s wort and paroxetine were equally effective in preventing relapse in continuation of treatment after recovery from moderate to severe depression. And that St. John’s wort was an important alternative treatment option for long-term prevention of depression.1059 2. St. John’s wort reduces stress. St. John’s wort is licensed in Germany to treat anxiety, depression and sleep disorders. But scientists and researchers are still working on what in this plant provides the anxiolytic effects. The anti-anxiety effects of St. John’s wort have been attributed to the binding affinity of at least 10 different extracts of the herb. Including naphthodianthrones like hypericin, flavonoids, xanthones, and bioflavonoids for adenosine triphosphate (ATP). GABAA, GABAB and glutamine receptors, as well as the inhibition of monoamine Oxidase-A and -B activity. And synaptic uptake of serotonin, dopamine and norepinephrine.1060 All we know for sure at this point is that St. John’s wort works to help alleviate some forms of anxiety. One German study ran a multicenter, randomized, placebo controlled, 6-week trial comparing the efficacy of St. John’s wort extract LI 160 (600 mg/day), and placebo in 151 out-patients suffering from anxiety. The data from the trial shows that St. John’s wort extract (LI 160) has superior effectiveness in controlling anxiety symptoms. And tolerability of the extract was excellent.1061 How things go bad Depression can be experienced at any age. Imbalances in neurotransmitters including serotonin, dopamine, and norepinephrine can affect everything from cognition to mood. ↓ Memory, recall, reaction time and mood diminish ↓ Neuroreceptors decline ↓ Neurotransmitters levels decline ↓ Anxiety, panic attacks, stress and insomnia rise

↓ Neuroplasticity declines degrading long-term potentiation Under conditions of depression and chronic stress your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition, and decision-making all suffer as a result. St. John’s wort benefits St. John’s wort inhibits synaptic uptake in your brain of serotonin, dopamine, and norepinephrine with approximately equal affinity. Research shows that St. John’s wort also has an affinity for adenosine (ATP), GABA and glutamate receptors. And in the lab, scientists discovered it downregulates beta-adrenergic receptors and upregulates serotonin receptors.1062 Adrenergic receptors are a class of G protein receptors that are targets of the catecholamines like norepinephrine and epinephrine (adrenaline). This upregulation and downregulation of neurotransmitter concentrations are in areas of the brain implicated in depression. And finally, neuroendocrine studies show that St. John’s wort is involved in the regulation of genes that control HPA-axis function. Also contributing to the antidepressant action of this herb.1063 Much of the therapeutic activity is attributable to St. John’s wort active phytochemical ingredients hypericin, hyperforin and several flavonoids.1064 This novel mechanism of action is unlike any other single pharmaceutical antidepressant or nootropic. And underlies St. John’s wort’s profound effect on depression. St. John’s wort also has strong antibacterial1065 and antiviral1066 properties. And St. John’s wort inhibits tumor cell growth.1067 Research shows that St. John’s wort extracts decrease oxidative stress and prevent neurotoxicity, and inflammation. And may be an effective treatment for oxidative stress-related neurodegenerative disorders like Parkinson’s and Alzheimer’s.1068 St. John’s wort shows promise as an anti-inflammatory.1069 Thousands of years of clinical use shows St. John’s wort works as a wound-healing agent. And St. John’s wort even helps reduce the effects of opium dependence by reducing withdrawal symptoms.1070 Handy if you’re coming off of opiates. How does St. John’s wort feel? If you have had problems with using SSRI prescription antidepressants, St. John’s wort extract may be a good option for you. St. John’s wort does not produce the same side effects as pharmaceutical antidepressants. Sex drive is not affected. No withdrawal symptoms when you stop taking St. John’s wort. Users of St. John’s wort extract say it often works sooner than expected and gets better over time.

St. John’s wort extract helps provide better focus, and fewer Obsessive-Compulsive Disorder (OCD) symptoms. Users report an end to procrastination, less irritation, and better mood. St. John’s wort extract takes the edge off situations that would normally stress you. Feelings of anxiety are less or non-existent. Women going through menopause report feeling more emotionally stable when using St. John’s wort extract. Mood swings are no longer an issue. If you deal with PTSD you may find that St. John’s wort extract will put a stop to the rage. And longterm depression could be a distant memory. If you are sure your depression is caused by a serotonin imbalance, you should feel the mood-lifting effects of St. John’s wort. But neuroscience is a complicated subject. And everyone’s body and wiring are different. St. John’s wort does not work for all types of depression or anxiety. If your depression is caused by a hormone imbalance, a depleted microbiome, an issue with dopamine levels or other neuroreceptor issue, you may not experience the benefit of St. John’s wort. And please, please do not combine St. John’s wort with prescription antidepressants! Serotonin Syndrome is real and could kill you. Literally. The Research The Politics of Treatment for Depression Most clinical studies using St. John’s wort for depression have been conducted in Europe. And were targeted in cases of mild to moderate depression. And then came a study done at Vanderbilt University in the US in 2001 which made headline news and created a ton of controversy. This study discredited the herb’s use in treating patients with major depression. I’m including this study to draw your attention to why we cannot always rely on “clinical studies” to study a nootropic’s efficacy in brain optimization. And why the nootropics community often resorts to personal experience, and the reviews of other neurohackers. This double-blind, placebo-controlled trial worked with 200 adult outpatients (mean age 42.4 years) who were diagnosed with major depression. Patients were randomly assigned to receive 900 mg per day of St. John’s wort extract or a placebo for 4 weeks. And if they did not respond, the dose was raised to 1,200 mg per day (or a placebo) for another 8 weeks. The researchers concluded that there was no significant change in patient depression scores. And that St. John’s wort was no better than placebo for treating major depression. Their conclusion was, “St. John’s wort was not effective for treatment of major depression”.1071

I bring this study up for one reason: the study was funded by Pfizer, the pharmaceutical manufacture of Zoloft. The leading synthetic antidepressant medication. In 2015, the FDA in the US pushed Pfizer Inc. to modify the safety warning for Zoloft. Linking Zoloft to causing heart defects in newborns. This in response to hundreds of lawsuits by women who say they weren’t adequately warned that Zoloft could cause defects in their newborns. Zoloft sales for Pfizer made the company $3.3 billion in 2005.1072 It seems to me that having a major pharmaceutical company funding the study of an herb that is in direct competition to one of their main profit-centers is a direct conflict of interest. And there was no way Pfizer was going to have a clinical trial show that St. John’s wort was as good as, or better than Zoloft. It’s also interesting that sales of St. John’s wort annual USA sales reached a peak of $315 million in 1998. But had declined to about $60 million by 2006.1073 Bad press strongly affected the sales of this natural antidepressant. And yet the sales of pharmaceutical antidepressants continue to rise. St. John’s wort as a Treatment for Mild-to-Moderate Depression A study at St. John’s Episcopal Hospital in New York compared St. John’s wort to the SSRI sertraline (Zoloft) in the treatment of depression. In this double-blind, randomized study, 30 outpatients (mean age 45.5 years) with mild to moderate depression received 600 mg per day of standardized St. John’s wort extract or 50 mg per day of sertraline for 1 week. This was followed by 900 mg per day of St. John’s wort extract or 75 mg per day of sertraline for another 6 weeks. The severity of depression symptoms was significantly reduced in both treatment groups. Clinical response was noted in 47% of patients receiving St. John’s wort. And 40% in patients receiving sertraline. The researchers concluded that St. John’s wort extract was at least as effective as sertraline in the treatment of mild to moderate depression.1074 St. John’s wort for Major Depression I include this study done in 2008 for using St. John’s wort as treatment for major depression as a response to the questionable study sponsored by Pfizer in 2001. This study done in Munich, Germany investigated whether extracts of St. John’s wort are more effective than placebo in treating major depression. And as effective with fewer side effects than standard antidepressant drugs. This study was a review of 29 trials including a total of 5,489 patients. It included 18 comparisons with placebo and 17 comparisons with synthetic “standard antidepressants”. The standard antidepressants

included tricyclic and SSRI antidepressants. The author’s conclusions reported that the available evidence suggests that St. John’s wort extracts were superior to placebo in patients with major depression. St. John’s wort extracts were similarly effective as standard antidepressants. And St. John’s wort extracts had fewer side effects than standard antidepressants.1075 St. John’s wort helps Obsessive-Compulsive Disorder A study done at the Dean Foundation for Health Research and Education analyzed 12 patients who had been diagnosed with OCD. Patients received 450 mg of St. John’s wort twice daily for 12 weeks. The study included weekly evaluations using three different Obsessive-Compulsive scales. And a monthly evaluation with the Hamilton Rating Scale for Depression. Changes in obsessive compulsive behavior occurred within one week of supplementing with St. John’s wort. And changes continued to improve over the course of the 12-week trial. 5 of the 12 patients were rated “much” or “very much” improved, 6 patients were rated “minimally” improved, and 1 person had no change in symptoms. The researchers concluded that St. John’s wort could be an effective treatment for ObsessiveCompulsive Disorder (OCD).1076 Dosage Notes St. John’s wort is available from local health food and vitamin stores and online. St. John’s wort comes in capsule, tablet, and powder form. It’s also available as tinctures, teas and oil-based lotions. Most St. John’s wort supplements are standardized to contain 3% hypericin. But the most recent clinical studies show that hyperforin is the constituent in St. John’s wort that has the most antidepressant action. Researchers say that the benefits of St. John’s wort are only applicable to standardized extracts such as LI 160, WS 5570/2, and ZE 117.1077 Check the labels and look for: • • •

Perika® which is WS 5570 extract Kira® which is LI 160 extract New Chapter SC27 who produce their own extract

There are reports and some clinical data which suggest that the photosensitivity caused by hypericin can cause cataracts and blindness. All the more reason to play it safe and go with a high quality St. John’s wort extract containing hyperforin.1078 Recommended doses for St. John’s wort extract: • •

St. John’s wort for anxiety: 900 mg twice daily St. John’s wort for mild to moderate depression: 300 mg 3-times daily

• • • • •

St. John’s wort for severe depression: 900 – 1800 mg daily St. John’s wort for OCD: 450 – 1800 mg daily for 12 weeks St. John’s wort for PMS: 300 – 900 mg daily for 2 menstrual cycles St. John’s wort for irritable bowel syndrome: 450 mg twice daily for 12 weeks St. John’s wort for nerve pain: three 900 mcg hypericin tablets for 2 treatment periods of 5 weeks each

Side Effects Side effects with St. John’s wort are generally mild and can include stomach upset, hives, skin rashes, fatigue, restlessness, headache, dry mouth, dizziness, and confusion. St. John’s wort can interfere with getting pregnant, or make infertility worse. It can make ADHD symptoms worse. Particularly if you’re taking Ritalin. St. John’s wort may increase the risk of psychosis in those with schizophrenia and may contribute to dementia in those with Alzheimer’s. St. John’s wort can interact with medications used during surgery. So if you’re anticipating surgery avoid St. John’s wort. Do not take St. John’s wort if you have bipolar disorder. Some St. John’s wort extracts can make your skin and eyes overly sensitive to sunlight. You should avoid sunlamps, tanning booths and tanning beds while using a St. John’s wort product containing hypericin. There is some clinical data showing that St. John’s wort products that contain hypericin may cause blindness.1079 St. John’s wort and Serotonin Syndrome Cytochrome P450 3A4 (CYP3A4) is a liver enzyme whose job is to oxidize small, foreign organic molecules and toxins so they can be removed from your body. Some substances, including St. John’s wort and grapefruit juice, affect the enzyme CYP3A4. And can amplify or weaken the action of those drugs and nootropics.1080 St. John’s wort interacts with tricyclic, SSRI and MAOI antidepressants. Taking St. John’s wort with these medications increases their action and could lead to serotonin syndrome which can be deadly. Do not take St. John’s wort with antidepressants including: • • •

Tricyclic: Amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil) SSRI: Citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil), fluoxetine (Prozac), sertraline (Zoloft) MAOI’s (Phenelzine (Nardil), tranylcypromine (Parnate)

St. John’s wort can reduce levels of antihistamines in your body. It can increase the risk of bleeding

when combined with Plavix and birth control pills. Do not use St. John’s wort with Warfarin as it can reduce its effectiveness. Drugs that suppress the immune system can lose their effectiveness with St. John’s wort. It should not be used with drugs that treat HIV and AIDS. St. John’s wort can increase the sedative effect of barbiturates, benzodiazepines (Valium), and triptans that treat migraines. St. John’s wort also interacts with antifungal drugs, statins, calcium channel blockers, and any other medication that is broken down by the liver. Which covers a lot of drugs and nootropics. Serotonin Syndrome is not to be messed with. An overload of serotonin in your brain can make you very sick. And can ultimately kill you. I’m not kidding here. If you suspect anything could cause problems if it’s increased or decreased in your system, do not use St. John’s wort. If your goal is to treat depression and mood issues, you have many other safer options available to you. Available Forms St. John’ wort is available in tablet, capsule, and powder form. Most are standardized to contain 0.3% hypericin. But the most recent clinical studies show that hyperforin is the constituent in St. John’s wort that has the most antidepressant action. Researchers say that the benefits of St. John’s wort are only applicable to standardized extracts such as LI 160, WS 5570/2, and ZE 117.1081 Check the labels and look for a product containing: • • •

Perika® which is WS 5570 extract Kira® which is LI 160 extract New Chapter SC27 who produce their own extract

St. John’s wort is also available in tinctures, teas, and oil-based skin lotions. Nootropics Expert® Recommendation St. John’s wort extract up to 900 - 1,800 mg per day I recommend using St. John’s wort extract as a nootropic supplement. But with the strongest warning I’ve issued for any nootropic mentioned in this book. Do not combine St. John’s wort with prescription antidepressants because the combination puts you in serious danger of Serotonin Syndrome. St. John’s wort may also nullify or amplify the effects of other drugs including nootropics in your stack. This is caused by the suppression or induction of certain enzymes in your liver. Check the “Side Effects” portion of this chapter. And do your research before using St. John’s wort if

you are taking any other medication or nootropic. Your body does not make St. John’s wort on its own. So to experience its antidepressant effects, you must take it as a supplement. St. John’s wort is especially helpful for those suffering from depression, anxiety and stress. Studies show it may help stop and reverse the devastating effects of stress on your brain, and body. St. John’s wort stacks well with SAM-e. You can safely take up to 1,800 mg of St. John’s wort daily if needed. Half the dose first thing in the morning. And the other half early afternoon. St. John’s wort can cause insomnia. So avoid taking it too late in the day.

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Sulbutiamine Sulbutiamine has been shown to boost motivation, improve focus, enhance memory and alleviate depression Sulbutiamine (isobutyryl thiamine disulfide) is a synthetic derivative of Vitamin B1 (thiamine). Thiamine was the first B Vitamin to be discovered by researchers. That’s why it’s called B1. Sulbutiamine is simply two vitamin B1 molecules joined together. This chemical bond helps thiamine more easily cross the blood-brain barrier. Japanese scientists first synthesized Sulbutiamine in an attempt to quell a health crisis within the Japanese population. After WWII, the Japanese diet largely consisted of rice. This left them deficient in several key nutrients including thiamine. Insufficient thiamine led to a central nervous system disorder called Beriberi. But supplementing with thiamine alone didn’t help. Because of its poor bioavailability. And a lot of thiamine was needed to cure Beriberi symptoms. Sulbutiamine is far more bioavailable than standard thiamine. It is fat-soluble (thiamine is watersoluble) which helps it more easily cross the blood-brain barrier. The discovery of Sulbutiamine cured the Japanese population of a life-threatening disease. And it has since been tested and used throughout the world with much success. Throughout this chapter I’ll refer to Sulbutiamine interchangeably with thiamine. Sulbutiamine is the stronger of the two, so it’s affects are amplified compared to standard thiamine. Thiamine is a coenzyme used by your body to metabolize food for energy. And to maintain proper heart, nerve, and brain function. Thiamine also helps digest and extract energy from food. It turns nutrients into adenosine triphosphate (ATP). ATP is the fuel used by your cell’s mitochondria. And thiamine helps convert carbohydrates into glucose. The energy your body uses for your brain and nervous system. One more thing about this miracle B-vitamin. Thiamine contributes to the development of myelin sheaths which wrap around the axons of neurons to protect them from damage and boost brain cell signaling. Your body does not produce thiamine on its own. So you must get it from food including beef, brewer’s yeast, legumes (beans, lentils), milk, nuts, oats, oranges, pork, rice, seeds, wheat, whole-grain cereals, and yeast. But thiamine has poor bioavailability. By synthesizing thiamine and producing Sulbutiamine you end up with a fat-soluble compound that is easily digested. And readily crosses the blood-brain barrier.

Sulbutiamine vs. Thiamine: What’s the Difference? Sulbutiamine is a synthetic version of Vitamin B1 (Thiamine). It is two B1 molecules chemically bonded together. Thiamine is water-soluble and does not easily cross the blood-brain barrier. Sulbutiamine is a fatsoluble compound that easily crosses the blood-brain barrier. Sulbutiamine functions in the body just like thiamine. But because it’s more bioavailable, it’s more effective than thiamine. How does Sulbutiamine Work in the Brain? Sulbutiamine boosts brain health and function in several ways. But two in particular stand out. 1. Sulbutiamine is a fat-soluble molecule that crosses the blood-brain barrier more readily than thiamine. Once in your brain, it increases levels of thiamine pyrophosphate (TPP). Thiamine pyrophosphate (TPP) is directly involved in the citric acid cycle (KREBS) in the brain. This cycle breaks fatty acids, amino acids and monosaccharides into smaller molecules that produce adenosine triphosphate (ATP) energy for your mitochondria. And provide the building blocks of the molecules needed to produce brain cells. A deficiency of TPP can eventually show up as Wernicke encephalopathy and Korsakoff syndrome. In our society this syndrome is typically caused by chronic alcoholism. But it can also occur after obesity (bariatric) surgery, Crohn’s disease, anorexia and if you’re on kidney dialysis. Symptoms of Wernicke-Korsakoff syndrome include confusion, inability to form memories, loss of memories and muscle coordination, confabulation (making up stories) and vision changes. And can ultimately (and very rapidly) lead to coma and death.1082 Less severe cases of thiamine deficiency include fatigue, weight loss, irritability and confusion. 2. Sulbutiamine also contributes to the production of the enzyme PDH which is essential in making the neurotransmitter acetylcholine. And for the synthesis of myelin, which forms a sheath around the axons of neurons. Ensuring these neurons can conduct signals.1083 The citric acid cycle and enzyme α–KGDH play a role in maintaining optimal levels of the neurotransmitters glutamate, and gamma–aminobutyric acid (GABA). When thiamine levels decrease, the activity of these enzymes are reduced.1084 How things go bad We depend on our diet for thiamine. Very little thiamine is stored in your body. And depletion can occur within 14 days. Thiamine deficiency can be caused by alcoholism, Alzheimer’s Disease, anemia, athletes who reduce

food intake, cancer, clogged arteries, Crohn’s disease, diabetes, diarrhea and kidney disease. And even a poor diet. ↓ Low thiamine levels can slow creation of ATP ↓ Low thiamine levels can cause problems with memory, learning, recall and perception ↓ Acetylcholine levels decline All of these changes can happen at any age. And are a product of the food we eat, what we drink, lifestyle habits, the air we breathe and more. So Sulbutiamine can help age-related cognitive decline, as well as a student looking to do better in school. By boosting acetylcholine, dopamine and GABA in the brain. And increased brain energy by fueling cell mitochondria with ATP. And building myelin sheaths that protect our neurons. Sulbutiamine benefits Sulbutiamine is directly involved in the citric acid cycle that creates adenosine triphosphate (ATP) energy within your mitochondria. Sulbutiamine also plays a role in maintaining optimal levels of the neurotransmitters glutamate, and gamma–aminobutyric acid (GABA). And contributes to the production of the enzyme PDH which is essential in making the neurotransmitter acetylcholine. Sulbutiamine will boost cognition, memory and decision-making. And has very effective anxiolytic (anti-depressant) qualities. How does Sulbutiamine feel? Sulbutiamine is a fat-soluble form of thiamine which crosses the blood-brain barrier. It has been shown to improve glutamatergic, cholinergic, and dopaminergic neurological transmissions. It may also increase the density of D1 dopamine receptors.1085 Nootropics users report: •

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Sulbutiamine as a study aid. On its own, Sulbutiamine seems to increase attention span for many neurohackers. And when combined with caffeine or any one of the racetams, many report being able to work effortlessly for hours on end. Study and work seems less stressful. Boost motivation. Sulbutiamine boosts motivation and many report gives them the drive they need for study or work. Increased focus. Sulbutiamine helps provide laser-like focus at work and school. Some report even with the most tedious of tasks. While staying in a very good mood. Sociability. Many users report being able to articulate thoughts, and improved speaking ability. Language and your vocabulary seem to flow effortlessly. Thoughts and ideas come with less effort. Improved mood. Personally, I’ve found Sulbutiamine to be more effective than any prescription

anti-depressant I’ve ever tried. And without the side effects. You should be able to experience the effects of Sulbutiamine soon after you take it. The Research Sulbutiamine Improves Mood A study at the University of Wales Swansea in the UK worked with 120 young adult females. Study participants took either a placebo or 50 mg thiamine for 2 months. Mood, memory and reaction times were monitored before and after taking the tablets. The results indicate that after 2 months of thiamine supplementation, the young females: • • • •

Were more clearheaded Felt more composed and energetic Reaction times improved Improved mood.1086 Sulbutiamine for Chronic Fatigue

If you deal with chronic fatigue, Sulbutiamine may be a better option than another cup of coffee. Or a stimulant. Researchers at the Hospital Saint-Antoine in Paris studied 326 patients. All suffering from chronic fatigue. Patients were given 400 mg or 600 mg of Sulbutiamine daily. Or a placebo in this double-blind, parallel-group study. Patients were tested on the 7th and 28th days of the trial. Those that used 600 mg of Sulbutiamine had less fatigue.1087 Sulbutiamine Improves Memory Poor memory is associated with low levels of choline activity in the brain. Choline is a precursor to the neurotransmitter acetylcholine (ACh). ACh transmission between neurons helps in memory formation. Scientists decided to find out if Sulbutiamine could help boost choline uptake. They gave a group of mice Sulbutiamine for 10 days, and then tested their memory. The findings suggested Sulbutiamine improved memory formation. And it was due to an increase in choline activity in the brain.1088 Another study in France involved giving Sulbutiamine or a saline solution to rats for 9 weeks. The results of this study concluded Sulbutiamine provided better working and episodic memory.1089 Sulbutiamine Improves Athletic Performance Many neurohackers use Sulbutiamine for a boost in physical energy. And it’s created some controversy in professional sports. The Moscow Anti-Doping Center analyzed 16,000 blood samples in a Russian lab in 2009. They were looking for anabolic steroids in athletes.

They found that 100 samples contained Sulbutiamine. These samples were collected in-competition. Indicating that Sulbutiamine was intentionally administered for its “ergogenic and mild stimulating properties”.1090 Sulbutiamine Improves Erectile Dysfunction One small study was conducted with 20 patients suffering from psychogenic erectile dysfunction. This type of ED is defined as the inability to achieve or maintain an erection because of psychologic factors. The men were given a prescription form of Sulbutiamine ‘Enerion’ for 30-days. 16 of the men showed significant improvement based on the international index of erectile function (IIEF). 3 of 6 men with arterial disorders in their penis showed that Sulbutiamine corrected the problem. The study concluded that erectile dysfunction can be effectively treated with Sulbutiamine.1091 Dosage Notes Recommended Sulbutiamine dosage is 400 mg to 1,000 mg per day. Higher doses should be split with one dose in the morning, and the other early afternoon. Some neurohackers warn about dosing Sulbutiamine too late in the day. It’s mild ‘stimulant’ qualities could interfere with sleep. If you’re just starting out with Sulbutiamine, I suggest starting with a low dose and see how your body reacts. Tolerance can be a problem with Sulbutiamine. So when taking it for extended periods, you may find it beneficial to cycle on and off the supplement. For example, take Sulbutiamine for 5 days, and take 2 days off before your next dose. Sulbutiamine powder tastes nasty. So you’d be advised to take it in capsule form. You can save on the cost of Sulbutiamine by making your own capsules. And Sulbutiamine is fat-soluble so take it with a tablespoon of unrefined coconut, or extra virgin olive oil for better absorption. Side Effects Sulbutiamine non-toxic. So is considered well-tolerated and safe. Side effects are rare but can include skin rashes and eczema-like outbreaks and higher doses. Sulbutiamine can also create mood swings. Particularly if you’re bipolar or are taking bipolar medication. If you take Sulbutiamine late in the day you may find it interferes with sleep. Some find it has mild stimulant effects. There are some reports that Sulbutiamine can be addictive. If you have addiction-like tendencies, you may want to be cautious about using this supplement. It does affect dopamine levels in the brain.

Available Forms Sulbutiamine is sold in tablet, capsule, and powder form. Tablets and capsules are usually 750 mg each. It’s sold as a prescription medication in some countries under the brand names Arcalion, Enerion, Bisibuthiamine, and Youvitan. Nootropics Expert® Recommendation Sulbutiamine 1,500 mg per day I recommend using Sulbutiamine as a nootropic supplement. Your body does not make Sulbutiamine on its own. So to get its benefits you must take it as a supplement. Sulbutiamine is especially helpful for those suffering from depression. Experience shows it helps stop and reverse the symptoms associated with depression. Likely because this nootropic helps boost the activity of dopamine, serotonin, GABA and glutamate in the brain. Personally, I’ve found Sulbutiamine to be more effective (and safer) than any prescription antidepressant I’ve ever tried. Sulbutiamine is also particularly helpful to students and executives who want to boost cognition, learning and memory. Sulbutiamine can produce a noticeable increase in mental clarity. And give you a significant energy boost physically and mentally. You’ll feel more awake and alert. Without the side effects you’d get from stimulants like caffeine. Sulbutiamine also stacks very well with racetams like Piracetam and Aniracetam.

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Sulforaphane Sulforaphane is known for helping with autism, recovery from Traumatic Brain Injury (TBI), preventing the progression of Alzheimer’s and Parkinson’s, and is anti-cancer Sulforaphane (1-isothiocyanato-4-methylsulfinylbutane, SFN) is a potent phytochemical. Phyto is the Greek word for plant. In other words, Sulforaphane is a phytochemical made by plants. Sulforaphane is found in cruciferous vegetables such as cabbage, kale, cauliflower, and radishes in the form of glucoraphanin and myrosinase. But it’s most plentiful in broccoli. Sulforaphane is synthesized in your gut through a hydrolysis reaction that involves the enzyme myrosinase and glucoraphanin. Sulforaphane is needed to ensure your body gets enough sulfur. A mineral critical for the synthesis of cysteine and methionine which are needed to produce your master antioxidant glutathione. Sulforaphane is one of the most frequently studied plant-derived isothiocyanate organosulfur compounds. And has been reported to provide a wide range of effects. It is antioxidant, antiinflammatory, antimicrobial, anticancer, anti-aging, neuroprotective, and antidiabetic.1092 A major area of research on sulforaphane is its effect on autism. Studies have shown that sulforaphane improves behavior in young people with autism.1093 Sulforaphane can help reduce cognitive impairment associated with Alzheimer’s disease. It helps prevent potential damage that can be caused by the β-Amyloid aggregation associated with Alzheimer’s and Parkinson’s.1094 Sulforaphane easily crosses the blood-brain barrier. And is a powerful defense against oxidative stress and neuronal damage caused by traumatic brain injury (TBI).1095 Studies show that if Sulforaphane is taken within one hour of traumatic brain injury it will improve spatial learning and memory and reduce working memory dysfunction.1096 Studies have also found that sulforaphane may protect against changes in gene expression that if left unchecked could lead to prostate cancer progression.1097 How does Sulforaphane Work in the Brain? Sulforaphane boosts brain health and function in several ways. But two in particular stand out. 1. Sulforaphane reduces oxidative stress. Mitochondrial dysfunction has been associated with the accumulation of Reactive Oxygen Species (ROS) within cells, which, when not properly scavenged, may lead to oxidative stress. Your immune system is designed to produce enzymes that scavenge ROS which prevents oxidative stress.

Immune system dysfunction has been observed in autism spectrum disorder (ASD). And high levels of ROS which causes oxidative stress are present in those with autism.1098 Sulforaphane boosts your body’s antioxidant defense mechanism, which protects against oxidative stress and maintains normal and healthy cellular function. Those with ASD who boost their intake of sulforaphane show improvement in social communication, unusual behavior, and self-regulation behavior. 2. Sulforaphane is anti-aging. Neurological disorders are the leading cause of death and disability worldwide. And most of these disorders share mutual causes such as oxidative stress, mitochondrial dysfunction, neuroinflammation, protein misfolding, ecotoxicity, and neuronal damage. All these disorders are common targets of the nuclear factor erythroid 2 related factor 2 (Nrf2) signaling cascade. Nrf2 is the main regulator of redox balance and cellular detox responses and stimulates your cellular defense mechanism.1099 And Nrf2 blocks oxidative stress and production of reactive oxygen species (ROS). Sulforaphane protects against these neurological disorders by regulating the Nrf2 pathway.1100 So, using Sulforaphane as nootropic supplement, you get the anti-aging protection against oxidative stress, which if left unchecked can lead to Alzheimer’s, Parkinson’s, multiple sclerosis, and other neurodegenerative diseases.1101 How things go bad Sulfur is the 3rd most abundant mineral in your body. You need sulfur to build and repair your DNA. And for healthy skin, ligaments, and tendons. And sulfur protects your cells from oxidative stress. Sulforaphane from your diet or as a nootropic supplement provides the sulfur you need to maintain healthy cognitive function. Providing ongoing protection against neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. If you do not consume sulforaphane, it can be difficult to get enough sulfur. Putting yourself at risk for: ↓ Low levels of antioxidants which lead to free radical damage ↓ Poor signaling of antioxidant defense systems ↓ Decreased cognitive function ↑ Increase risk for neurodegenerative disease

↑ Increased oxidative stress ↑ Increased inflammation ↑ DNA damage Supplementing with Sulforaphane can help maintain healthy brain function throughout your life. Sulforaphane benefits Turns out that when your mother told you to eat your broccoli because it is good for you, she was right! Sulforaphane can protect your brain from oxidative stress that if left unchecked can lead to Alzheimer’s or Parkinson’s. Sulforaphane acts as an antioxidant which help scavenge free radicals and support a healthy immune system. And has the potential to improve some domains of cognitive function in patients with schizophrenia. Sulforaphane is used by men worldwide to protect against and even reverse prostate cancer. And its anti-cancer functions are now recognized as effective for possibly preventing other types of cancer as well.1102 Sulforaphane has been shown to provide protection against ultraviolet (UV)-induced skin damage making it an anti-aging compound. And has potential for use in anti-aging drugs and cosmetics.1103 And studies have demonstrated the use of Sulforaphane for providing protection from Traumatic Brain Injury (TBI). And is a potential candidate for therapy for Traumatic Spinal Cord Injury.1104 How does Sulforaphane feel? Neurohackers report feeling energized when they take Sulforaphane. People who have been diagnosed as pre-diabetic say it helps them feel less fatigued, more energetic. Others say using Sulforaphane as a nootropic helps their mental health. They feel an improvement in their overall feeling of wellbeing. Many people say that Sulforaphane boosts cognitive function. They say it helps them think more clearly. Parents of autistic children report that Sulforaphane helps their children stay calm and focused. They report improved behavior. People with rheumatoid arthritis report that their symptoms are reduced when they consistently use Sulforaphane as a nootropic. Sulforaphane also offers better gastric health. Some people report that it provides relief from the symptoms of GERD/acid reflux. Neurohackers with traumatic brain injury say Sulforaphane helps reduce their feelings of anxiety.

And most report that taking Sulforaphane as a nootropic supplement is a great alternative if you don’t like eating broccoli or Brussels sprouts! Sulforaphane Clinical Research Hundreds of clinical studies have been conducted with Sulforaphane. Researchers found benefits that range from improvement in autism symptoms to cancer prevention. And from improvement of Alzheimer’s symptoms to the reduction of diabetic complications. Sulforaphane for autism A clinical trial done by researchers in Massachusetts showed that Sulforaphane improved behavior in young men with autism spectrum disorder (ASD). In a placebo-controlled, double-blind, randomized trial, 29 young men (aged 13-27) with moderate to severe ASD received Sulforaphane derived from brussel sprouts or a placebo daily for 18 weeks. Parents and caregivers evaluated their behavior using the Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS). Study doctors evaluated them using the Clinical Global Impression Severity scale (CGI-S). The young men who received Sulforaphane showed a substantial improvement in behavior. There was a 34% improvement on the ABC, and a 17% improvement on the SRS. Using the CGI-I measure, 46% showed significant improvement on social interaction. 54% on aberrant behavior. And 42% on verbal communication.1105 In another study, the same researchers looked at 57 children with ASD, aged three to 12 years old. 28 children were given Sulforaphane for 15 weeks, followed by no treatment for six weeks. The other 29 children received a placebo. Researchers in this study found that Sulforaphane improved the behavior of children using the ABC measure. But improvement on the SRS measure was not as dramatic as in the first study. They didn’t measure the CGI-I in the second study. The researchers pointed out that Sulforaphane is very safe. And it has been shown to lower oxidation levels, improve antioxidant action in the body, increase glutathione production, and lower neuroinflammation. All abnormalities that are associated with autism. Researchers concluded that Sulforaphane shows promise for helping people with autism.1106 Sulforaphane for Alzheimer’s Researchers are starting to propose human trials for Sulforaphane’s effect on Alzheimer’s disease. They haven’t been completed yet. But several studies involving animal subjects have been done. In one study, 48 mice were divided into three groups. One control group, one group with Alzheimer’s disease (AD), and one group with AD being treated with sulforaphane.

The Alzheimer’s group receiving sulforaphane had lower levels of harmful β-Amyloid deposits in their brain. They also had higher levels of glutathione peroxidase that helps protect the brain from free radical damage. The mice treated with sulforaphane had better performance in a water maze and open field test. This showed that their brains were functioning better than the mice who didn’t get sulforaphane. Researchers concluded that sulforaphane should be considered for use in preventing Alzheimer’s disease. And in therapy for those who already have it.1107 Sulforaphane helps prevent cancer The diagnosis of prostate cancer has increased because of increased PSA testing and an aging population. And up to 48% of cases may exhibit PSA progression after a subsequent follow up exam. But because of the risks associated with cancer treatment many men choose a program of “active surveillance” until there is evidence of cancer progression. The problem is there is no medical intervention for men who have chosen active surveillance that could reduce their risk for cancer progression. Thankfully, we have a natural solution that is proving to be highly effective. And that solution uses natural nootropic supplements like Sulforaphane. A study called the Effect of Sulforaphane on Prostate CAncer PrEvention (ESCAPE) was a randomized, double-blinded 3-arm parallel trial conducted in the UK. The study looked at how Sulforaphane affects prostate cancer. In this study involving 49 patients, they gave broccoli soup to men with low-risk or intermediate-risk prostate cancer. Patients were split into three groups. All groups were required to eat 300 mL of broccoli soup every week for 12 months. Broccoli contains high levels of glucoraphanin, which is a precursor to Sulforaphane. Each group ate soup with a different level of glucoraphanin concentration. Then researchers measured gene expression in biopsied prostate tissue at the beginning of the trial. And at the end of the trial. A change in gene expression could indicate a progression in cancer development.1108 Patients in the group that ate the highest levels of glucoraphanin had the healthiest gene expression. And showed higher levels of Sulforaphane in their circulation. Researchers concluded that Sulforaphane helps reduce the risk of cancer progression.1109 Sulforaphane Recommended Dosage Recommended Sulforaphane dosage is 35-60 mg per day. But Sulforaphane supplements vary so check the label or manufacturer’s website for dosage specific to the supplement you are using.

Sulforaphane Side Effects Sulforaphane is non-toxic and safe when consumed in its raw form from broccoli, broccoli sprouts, or kale. When taken as a nootropic supplement, Sulforaphane has few if any side effects if it’s taken at recommended dosages. More is NOT better and may be toxic. Sulforaphane rarely causes increased gas, constipation, or diarrhea. Sulforaphane is safe during pregnancy or breastfeeding when taken from a whole food source. The safety of Sulforaphane as a supplement is not known during pregnancy and breastfeeding so should be avoided. Sulforaphane is a source of Sulphur so your supplement may smell nasty depending on how it is manufactured. Type of Sulforaphane to Buy Sulforaphane is available in tablets, capsules, or powder. Dosage for each capsule varies widely, so read the label to know how many you need to take to get the recommended dose of 35 - 60 mg. Many formulations include the enzyme myrosinase. The glucoraphanin in broccoli combines with myrosinase in your gut to form Sulforaphane. TrueBroc® is patented form of glucoraphanin extracted from broccoli seeds using a hot water process. This patented Sulforaphane supplement is manufactured in Baltimore and licensed to supplement manufacturers for use in their product. Avmacol® by Nutramax Laboratories is a patented broccoli seed extract (Glucoraphanin) & Myrosimax® (active Myrosinase enzyme) which when digested produces Sulforaphane in your gut. Manufactured in Maryland and licensed to major supplement manufacturers. BrocColinate® by Numedica uses a patented CO2 extraction method to get Sulforaphane Glucosinolate from broccoli with added Myrosinase which is a key enzyme needed to convert Sulforaphane Glucosinolate into Sulforaphane in your small intestine. Nootropics Expert® Recommendation Sulforaphane 35-60 mg per day I recommend using Sulforaphane as a nootropic supplement. Your body does not make Sulforaphane on its own. You can get glucoraphanin from cruciferous vegetables or a nootropic supplement so your body can synthesize Sulforaphane using the enzyme myrosinase. Sulforaphane plays a powerful role in cell detoxification and the regulation of a healthy antioxidant defense system.

Sulforaphane may be especially helpful in you are dealing with autism. Sulforaphane provides antioxidant, anti-inflammatory, antimicrobial, anticancer, anti-aging, and antidiabetic benefits. Sulforaphane as a nootropic boosts cognition, helps support recovery from traumatic brain injury (TBI), and helps regulate mood. Sulforaphane protects against neurodegenerative diseases such as Alzheimer’s and Parkinson’s. And helps prevent cancer cell growth. It’s safe to use 35 – 60 mg of Sulforaphane per day. But some labels may be confusing because it will include much higher doses of the precursor glucoraphanin which makes Sulforaphane. So always check the label for dosage recommendations from the manufacturer of the supplement.

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Taurine Taurine is anti-anxiety, relieves chronic fatigue, promotes mitochondrial health, supports cellular energy, helps you sleep, and is anti-aging Taurine (2-aminoethane-sulfonic acid) is one the most abundant amino acids in your brain, spinal cord, eyes, and nearly every tissue in your body. Every region of your brain including the retina in your eyes contains or takes up taurine. You may be familiar with taurine only because it’s a featured ingredient in popular energy drinks like Red Bull, Rock Star, NOS, Amp, Full Throttle, and Monster. Occasionally we’ll see a story about sudden death or seizure from consuming as few as 3 – 4 cans of some energy drink. And because taurine is the featured ingredient many assume that taurine is the problem. Turns out that adding taurine to your nootropic stack is perfectly safe. The hidden issue often missed in the news is energy drink caffeine content ranging from 80 – 300 mg per can.1110 Everyone from athletes to exhausted soccer moms grab a Red Bull® to improve performance and make it through their day. But a better option is to avoid the sugar-laden energy drink. And stack a taurine supplement with a cup of coffee or green tea. For a similar effect. Without the negatives. Taurine functions as a neurotransmitter and neuromodulator in your brain. Activating GABA and glycine receptors which affects memory and mood and prevents seizures.1111 Taurine protects brain cells by reducing intracellular free calcium (Ca2+) concentrations.1112 It is a potent antioxidant, protects from mitochondrial dysfunction, modulates energy metabolism within cells, modulates genes to induce longevity, inhibits cellular stress associated with Alzheimer’s, acts as ‘quality control’ in brain cell health, and protects against stroke.1113 Taurine increases stem cells and progenitor cells (neural precursor cells) in your brain including the aging hippocampus and increases the survival of newborn neurons (neurogenesis).1114 Taurine is synthesized in your body from methionine and cysteine via cysteinesulfinic acid decarboxylase (CSD).1115 Taurine is a “conditional” amino acid because some of this amino acid is synthesized naturally in your body. And you get the remaining taurine your body requires from eating seafood, meat, poultry, and eggs. Taurine was discovered by German scientists Friedrich Tiedemann and Leopold Gmelin in 1827 who first extracted it from ox bile. It’s named after the Latin taurus which means bull or ox.

Since taurine is found almost exclusively in animal-based foods, many vegans and vegetarians are at risk for taurine deficiency.1116 Science also shows that taurine levels decline with age.1117 Possibly because the aging body and brain cannot supply enough of the precursors required to synthesize taurine.1118 The structure of taurine has two primary differences from essential amino acids. First, taurine’s amino group is attached to a beta-carbon instead of an alpha-carbon. And second, the acid group in taurine is sulfonic acid, instead of carboxylic acid like in other amino acids.1119 Because of this distinctive structure, taurine is not used in the synthesis of proteins in your body and brain. Instead, it provides a host of other benefits which we’ll cover in this review. The more we learn about taurine, the more we realize it is one of the most essential substances in the human body. After extensive animal studies showing all the benefits of taurine, scientists in Japan were curious if there was a correlation in human health. Using data from a WHO study covering 61 populations in 25 countries they confirmed that populations with the highest levels of taurine in their system lived the longest.1120 As a nootropic, taurine is essential for minimizing damage from beta-amyloid proteins associated with Alzheimer’s, protecting against environmental toxins, preventing mitochondrial dysfunction, and supporting the inhibitory GABA system. Taurine is needed for promoting long-term potentiation for memory formation, reducing brain inflammation, stimulating growth of new neurons (neurogenesis), and protecting your brain from the damaging effects of stroke. How does Taurine work in the brain? Taurine boosts brain health and function in several ways. But two in particular stand out. 1. Taurine may help anxiety and depression. If you deal with anxiety or depression, you know the negative effects on learning, work and your quality of life. Supplementing with taurine as a nootropic may help.1121 Research shows that taurine may help alleviate depression by changing depression-related signaling cascades in the hippocampus.1122 One human study with 121 bipolar patients aged 18 – 25 demonstrated a reduction in manic episodes when supplemented with taurine.1123 And several animal studies have shown taurine nootropic supplementation may help in the clinical treatment of anxiety. By modulating the GABA and glycine receptors in the brain. And preventing neurotoxicity and mitochondrial energy failure.1124

2. Taurine is anti-aging. Studies show that taurine levels fall as you get older. And supplementing with taurine seems to slow the brain aging process.1125 Taurine protects brain cells from pesticides and heavy metals such as lead.1126 It helps prevent mitochondrial dysfunction and regulates calcium levels.1127 And taurine prevents toxicity by reversing declines in the inhibitory GABA system.1128 Taurine supplementation reduces inflammatory processes caused by excessive iron accumulation that can lead to Alzheimer’s and Parkinson’s.1129 And it stops Amyloid-β from damaging mitochondria by activation of Sirtuin 1 (SIRT 1) which helps prevent Alzheimer’s.1130 Taurine also plays a critical role in creating new brain cells (neurogenesis). Research has found that taurine activates dormant stem cells in the brain.1131 And boosts the survival of new neurons which results in an increase in adult brain cells. How things go bad Some taurine is produced in your body from methionine and cysteine. But the remainder must come from your diet. If you are vegan or vegetarian, chances are high that you are not getting enough taurine. Diseases such as diabetes, cancer, liver disease, kidneys or heart can also deplete taurine. As can deficiencies in Vitamin B6 (P-5-P), zinc, magnesium, and Vitamin A. And eating food containing monosodium glutamate (MSG). Insufficient taurine means: ↓ reduced GABA can lead to anxiety and depression ↓ vision problems ↓ oxidative stress destroys neurons and synapses ↓ insulin resistance ↓ Brain-derived neurotrophic factor (BDNF) declines Taurine is one of the least expensive nootropic supplements there is. So if there the slightest doubt you are getting enough taurine then add it to your nootropic stack. Taurine benefits Taurine is the most abundant amino acid that you’ve never heard of. Strong evidence suggests taurine could be the secret factor in the world’s longest-living populations.1132 Studies show taurine: • • •

Critical for normal human brain development1133 Prevents mitochondrial dysfunction within brain cells Supports GABA in your brain preventing neurotoxicity & stress

• • • • • •

Reduces inflammation that can lead to Alzheimer’s and Parkinson’s Stimulates neurogenesis which is anti-aging Shields brain cells from stroke-induced brain cell damage Prevents beta-amyloid damage that could lead to Alzheimer’s Protects brain cells from heavy metals and pesticides Needed along with NMDA and dopamine receptors for long-term potentiation needed for longterm memory formation1134

And here we’re only investigating taurine’s effects on your brain. This essential amino acid can also restore insulin sensitivity, mitigate diabetic complications, reverse symptoms of heart disease, prevent and treat fatty liver, and reverse tinnitus. If you are interested in living a longer, healthier, and more active life, consider adding taurine to your nootropic stack. How does Taurine feel? Neurohackers report that supplementing with taurine is a simple way to support energy levels. Sleep is better, and taurine may be a safe alternative to prescription sleep meds. Most people using taurine report sharper eyesight. Muscle pain is reduced, less depression, and no more insulin resistance. Some report that adding taurine to their nootropic stack helped relieve chronic fatigue syndrome. Supplementing with taurine is effective for lowering blood pressure and reducing the occurrence of atrial fibrillation. If you have issues after eating food containing monosodium glutamate (MSG), taurine can help eliminate the headache and nausea. Taurine Clinical Research Taurine for autism Autism spectrum disorder is thought to be associated with oxidative stress caused by reactive oxygen species (ROS). So oxidative stress could be a potential target for therapeutic intervention for autism. Methylation capacity, sulfate levels, and total glutathione levels are decreased in autism. On the other hand, oxidative glutathione, and the ratio of oxidative to reduced glutathione are increased. So decreasing oxidative stress might be a potential treatment for autism.1135 Taurine is a well-known antioxidant and regulator of inflammation. Researchers in New York tested 66 children aged 1.5 – 11.5 years who were diagnosed with autism. And the controls in this study were the kids’ healthy siblings and parents. The study found that 21 out of 66 autistic children had low taurine concentrations. The researchers

concluded the data implied that taurine may be a valid biomarker for at least some with autism.1136 Taurine may help ADHD Studies have shown low dopamine in the prefrontal cortex and striatum segments of the ADHD brain. A very recent study conducted in Taiwan revealed that high-dose taurine calmed hyperactive behavior and brain signaling in ADHD rats. Taurine significantly affected dopamine transporter levels, dopamine uptake and brain-derived neurotrophic factor (BDNF) expression.1137 Mounting evidence in ADHD research also suggests a strong relationship between inflammation and ADHD. Elevated levels of inflammatory cytokines such as interleukin (IL)-1 and C-reactive protein are turning out to be diagnostic markers of ADHD. These cytokines induce changes in dopamine and norepinephrine in the prefrontal cortex. A recent study in Taiwan showed that high-dose taurine significantly reduced interleukin (IL)-1 and Creactive protein which in turn reduced hyperactive behavior.1138 Taurine for OCD Studies show that patients with OCD have increased glutamate activity and decreased GABA in the brain. And it could be genetic. One specific gene (SLC1A1) codes for transporters to clear glutamate from synapses, and boost GABA production.1139 If you are missing this gene, you’ll have problems with glutamate and GABA and likely experience symptoms of OCD. GABA plays a critical role in regulating excitability in neuronal networks in your brain. Taurine has been proven to activate GABA receptors and even boost GABA levels in your brain.1140 Helping to reduce symptoms of OCD. Taurine for epilepsy Read the reviews of taurine supplements and now and again you’ll see someone mention that consistent use of taurine reduces the severity and number of seizures they experience. Imbalances between excitatory and inhibitory neurotransmitters appear to be the mechanism of epileptic seizures. And taurine serves as an inhibitory neuromodulator. GABA is the primary inhibitory neurotransmitter in your brain. So the regulation of GABA plays a prominent role in preventing excitability and seizures. Taurine is a GABAA receptor agonist. High-doses of taurine activate this receptor as well as the glycine receptor which both suppress neuronal firing. Several clinical studies have been conducted to test the efficacy in using taurine to control epilepsy.

Reviews are mixed as only about 1/3 of patients respond favorably to taurine therapy.1141 So if you’ve tried everything else with little success you may want to give taurine a try. Taurine Recommended Dosage Recommended taurine nootropic dosage is 500 mg – 2 gm per day. The safe upper limit for taurine is 3 gm per day.1142 Instead of getting your taurine from an energy drink, try a taurine supplement with a cup of coffee or tea, and a high-quality B-Complex supplement. You’ll feel better and get the same benefit. Taurine is rapidly absorbed and used in your body and brain. But studies show that a single dose won’t do much in providing a benefit you can feel. Continual, daily, long-term nootropic usage of taurine builds and the maintains adequate levels of taurine in your system.1143 With very few exceptions, high doses of taurine are well tolerated without adverse side effects.1144 Taurine Side Effects Taurine is well-tolerated and safe for most people. And should not cause any side effects. High taurine dosage should be avoided if you are dealing with bipolar disorder because it could make your symptoms worse. Type of Taurine to buy Taurine is available in capsules and powder form. Taurine capsules are usually 500 or 1000 mg each. Avoid trying to get your taurine from energy drinks because the dose is too low for any nootropic benefit. And they are loaded with sugar, caffeine, and other ingredients that are contrary to good health. Nootropics Expert® Recommendation Taurine 500 mg – 2 gm per day I recommend using taurine as a nootropic supplement. Your body does make some taurine on its own. But the rest must come from meat, poultry, seafood, or dairy. Or a nootropic supplement. Taurine is especially helpful for relieving anxiety and stress. If you haven’t had much luck with prescription anti-anxiety meds or antidepressants, or other nootropics for anxiety, you may want to try taurine. For antiaging benefits, and a longer, healthier life you should add taurine to your nootropic stack.

Taurine is essential for a healthy brain, heart, muscles, eyes and hearing. Taurine is particularly effective for those using levodopa to treat Parkinson’s Disease because this drug depletes taurine in your body.1145 Doctors sometimes recommend dosages of taurine up to 6 grams per day for treating high blood pressure, diabetes, congestive heart failure, anemia, cystic fibrosis and after surgery. But for most neurohackers, up to 2 grams per day of taurine is adequate. Just avoid trying to get your daily taurine dose from energy drinks. The dose is too low and the risk from the other ingredients in these drinks is too high.

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Tryptophan Tryptophan has been shown to help alleviate anxiety, depression, ADHD, SAD, OCD, PMS, memory loss, and pain Tryptophan is an essential amino acid and precursor to serotonin, melatonin and niacin (Vitamin B3) in your body. The enzyme Tryptophan hydroxylase converts Tryptophan into 5-HTP (5-hydroxytryptophan). The decarboxylation of 5-HTP to serotonin is dependent on the presence of Vitamin B6, and pyridoxal 5’-phosphate (P5P). The further conversion of serotonin into melatonin requires the presence of SAM-e (S-Adenosyl-Lmethionine). Serotonin is often referred to as the “happiness molecule”. Low serotonin levels can result in pain, insomnia, depression, seasonal affective disorder, and chronic fatigue. For your body to manufacture serotonin, it needs an adequate supply of the natural amino acid Tryptophan. As a nootropic supplement, Tryptophan is used for anxiety, ADHD, depression, insomnia, memory loss, pain, and eating disorders.1146 Tryptophan is found in abundance in oats, bananas, dried prunes, milk, tuna, cheese, bread, chicken, turkey, peanuts, and chocolate. Eating food containing Tryptophan will increase levels of this amino acid in your body. But not necessarily boost serotonin levels in your brain. Here’s why… Tryptophan is one of 8 essential amino acids and has the lowest concentration in the body of all the amino acids. Tryptophan requires and competes for active transport to the brain. And competes for the same receptors as the other amino acids. Research has also found that serotonin levels are enhanced by carbohydrates in your meals because insulin release accelerates the serum removal of some of the amino acids that Tryptophan is competing with. And if your meal has a higher percentage of proteins, it also slows serotonin elevation in your brain.1147 Since Tryptophan from food has issues working its way to your brain to make serotonin, why not skip that step and supplement with 5-HTP instead? Tryptophan and 5-HTP both penetrate the blood-brain barrier. And 5-HTP is the intermediate step in serotonin synthesis. See my chapter on 5-HTP for more on why supplementing with 5-HTP instead of Tryptophan is not such a good idea. A lack of bioavailable Tryptophan in your body can have a big impact on your life. Low levels of

Tryptophan and serotonin imbalances in the brain are associated with ADHD. Studies have found that children with ADHD have 50% lower than average levels of Tryptophan.1148 Low levels of Tryptophan can result in short- and long-term memory loss. Supplementing with Tryptophan has been found to improve memory in healthy adults. How does Tryptophan work in the Brain? Tryptophan boosts brain health and function in several ways. But two in particular stand out. 1. Tryptophan boosts memory. Tryptophan’s main nootropic mechanism of action is as a precursor to the neurotransmitter serotonin. Other neurotransmitters such as melatonin, dopamine, norepinephrine and beta-endorphin increase following Tryptophan supplementation.1149 Research shows that Tryptophan and serotonin play a significant role in memory. Enhanced brain serotonin has been shown to improve cognitive performance in animals and humans. And decreasing levels of serotonin through Tryptophan depletion impairs cognition. A study done in Pakistan assessed memory in rats following Tryptophan administration. The rats received Tryptophan doses of 50 and 100 mg/kg of body weight for 6 weeks. The study showed significant improvement in memory of rats following both doses of Tryptophan.1150 2. Tryptophan enhances mood. As a precursor to serotonin, Tryptophan can have a significant effect on mood. Supplementing with Tryptophan has been found to increase not only serotonin, but growth hormone and prolactin as well. Researchers infused 11 healthy male subjects with doses of 5, 7.5 and 10 grams of Tryptophan. And then monitored their hormonal and behavioral responses. Tryptophan produced significant effects on mental and physical sedation but did not increase levels of tranquilization. Tryptophan provided a calming effect without knocking these guys out even at high doses.1151 How things go bad As we get older, our brain chemistry and energy metabolism changes. ↓ Tryptophan levels decline ↓ Tryptophan hydroxylase levels decline ↑ Stress, insulin resistance and age increase ↓ Magnesium and Vitamin B6 levels decline ↓ Neurotransmitter levels decline ↓ Concentration, working memory and executive function decline ↓ Appetite regulation, energy and alertness decline

All of these changes can happen at an age. And are influenced by declining Tryptophan levels. Very little dietary Tryptophan is available for protein and serotonin synthesis. And for many people this can be a problem. Anxiety, depression, ADHD, memory loss, binge eating, and a host of other mental and physical issues have been correlated with low Tryptophan levels. Tryptophan benefits Just living in our modern society seems to leave us irritable, stressed-out, and anxious. Worst case is problems sleeping, depression, aggressive behavior, reduced motivation, pain and even suicidal thinking. And all have been traced to not enough serotonin in our brain.1152 Serotonin, the happiness molecule relies on an adequate supply of Tryptophan for synthesis. Researchers now recognize that the role serotonin plays in psychiatric and behavior disturbances comes from Tryptophan depletion.1153 Tryptophan hydroxylase is the rate-limiting enzyme needed for serotonin production. And is involved in the conversion of Tryptophan to 5-HTP (5-Hydroxytryptophan) needed to make serotonin. This enzyme (Tryptophan hydroxylase) can be inhibited by stress, insulin resistance, magnesium or Vitamin B6 deficiency or increasing age. Tryptophan and 5-HTP can penetrate the blood-brain barrier. But Tryptophan requires active transport and competes for the same receptors with other amino acids including tyrosine, phenylalanine, valine, leucine, and isoleucine.1154 To complicate things even more, serotonin levels are enhanced by carbohydrates in our diet because insulin release accelerates serum removal of the amino acids competing for Tryptophan transport. And high levels of protein in our diet slows increase in serotonin.1155 So now you know why it’s helpful to add supplemental L-Tryptophan to your nootropic stack. How does Tryptophan feel? Many try L-Tryptophan the first time to cure insomnia or as an alternative to prescription sleep meds. Dosing L-Tryptophan in the evening will typically ensure you’ll feel great the next day. You should have more energy for working out. Anxiety levels should decrease. Happiness levels should rise. Tryptophan could help with memory. Music will sound better. Feelings of self-esteem will improve. Some neurohackers report being able to taper off prescription antidepressant meds by supplementing with L-Tryptophan. The Research

5-HTP and Tryptophan are natural alternatives for the treatment of depression. And often used as alternatives to prescription antidepressant treatments because they don’t come with the side effects associated with antidepressant drugs. But as neurohackers we don’t have a lot of research to help us decide if supplementing with Tryptophan makes sense. (If we base our decisions on clinical trials). Much of the research looks at finding out if low levels of Tryptophan are associated with depression and poor cognition. But there is very little clinical evidence that supplementing with Tryptophan will help reverse low Tryptophan levels. And if adding this nootropic to our stack will boost mood and cognition. Researchers at the University of Queensland in Australia decided to comb through the research to find out if clinical trials supported the natural health claims of using 5-HTP and/or Tryptophan for depression. The team located 108 trials of which only 2 studies involving a total of 64 people had sufficient data to qualify. The team concluded that the very limited data showed 5-HTP and Tryptophan better that placebo for alleviating depression. But that larger and more studies were needed before their widespread use could be recommended.1156 Low Tryptophan = Depression and Poor Cognition 20 patients in remission or partial remission from depression were studied in a double-blind, crossover design trial. Tryptophan was artificially depleted in these patients so scientists could look at the effects on cognition and mood. The research team found what we see in real life. Lower levels of Tryptophan had a negative effect on mood, their ability to process positive information, and attention.1157 Tryptophan Helps Manage Depression Serotonin has been recognized as the neurotransmitter that is key to managing depression for the last 30 years. Most of the prescription drug therapies for depression work by raising serotonin levels at the relevant synapses. We also know that Tryptophan is the immediate precursor to serotonin in the brain. So researchers, using a “what came first, the chicken or the egg” approach, decided to find out if low serotonin levels or low Tryptophan levels were to blame for depression symptoms. Researchers in China analyzed levels of Tyrosine, Tryptophan and serotonin in patients with major depressive disorder. And found that all three were decreased in depressed patients. (Note that Tyrosine is a precursor to dopamine in the brain).1158 The Center for Addiction and Health in Toronto conducted a randomized, double-blind, placebocontrolled trial with 30 depressed individuals. Treatment was fluoxetine (Prozac®) 20 mg per day, 2-4 grams of Tryptophan per day or a placebo for 8 weeks. Mood was assessed using the Hamilton Depression Rating Scale and the Beck Depression Index during

the trial. During the 1st week there was a significant decrease in depression in those who used fluoxetine or Tryptophan. At 4 weeks the research team recorded a disruption in sleep patterns for those using fluoxetine or a placebo. But not the Tryptophan group. The team concluded that combining 20 mg of fluoxetine with 2 g of Tryptophan was a safe protocol for treating depression. Patients experienced a rapid decrease in depressive symptoms. And the combination had a protective effect on sleep patterns.1159 DO NOT TRY THIS AT HOME. The trials combining Tryptophan with SSRI’s, SNRI’s and MAOI’s are all done under professional supervision. Remember, Tryptophan is a precursor to serotonin. And antidepressant meds also boost serotonin in the brain. When combined, serotonin levels are boosted even more. Herein lies the problem. If you increase serotonin too much, you put yourself in real danger of Serotonin Syndrome. Which can lead to all kinds of nasty side effects. Including death.1160 DO NOT combine Tryptophan with antidepressant meds unless you are doing so under the careful supervision of a doctor. It is much too dangerous attempting this on your own. Tryptophan Boosts Exercise Performance Ever wondered why you cut a workout session short even though physical fatigue wasn’t an issue? Researchers found it could be due to low Tryptophan levels. And its effects on serotonin in your brain. 20 healthy young men aged 21 years used a cycle ergometer at about 50% of their physical capacity for 10 minutes followed by maximum intensity exercise for another 30 minutes. This sequence was repeated 3-times, and after the 4th series, each participant continued at the highest speed they could sustain for 20 minutes. This protocol was performed twice: once with and once without Tryptophan. Researchers found peak power output during the last 20 minutes were higher on trials performed with Tryptophan than those who performed on a placebo.1161 Another trial in Spain recruited 12 healthy sportsmen who ran on a treadmill until exhaustion. Once while supplementing with Tryptophan and once with a placebo. Total exercise time, perceived exertion rate, maximum heart rate, peak oxygen consumption, pulse recovery rate, and excess post-exercise oxygen consumption were determined during the two trials. Total exercise time was nearly 50% greater after receiving Tryptophan than after receiving a placebo. Perceived exertion rate was lower when using Tryptophan. The researchers concluded that the longer exercise time could be due to increased pain tolerance as a result of Tryptophan supplementation.1162 Tryptophan Relieves Symptoms of Seasonal Affective Disorder

Seasonal Affective Disorder (SAD) is a form of depression experienced by many during the winter months. Symptoms include difficulty waking, decreased energy, weight gain, carbohydrate craving, difficulty concentrating, decreased libido, withdrawal, anxiety, depression and irritability. The first order of treatment is often light therapy. But many do not respond to light therapy typically because of a mutation in the melanopsin gene and the associated signaling pathway between the retina and the pineal gland.1163 The pineal gland in your brain is your source of melatonin which influences sleep cycles. Melatonin is synthesized from serotonin which is synthesized from Tryptophan.1164 So if light therapy doesn’t work, possibly supplementing with Tryptophan to stimulate production of serotonin and melatonin could be effective. Researchers at the University of British Columbia in Vancouver, Canada set out to find if Tryptophan could help those with Seasonal Affective Disorder (SAD) where light therapy failed. Patients were treated for 2 weeks using light therapy. Those who did not respond to light therapy were treated with 1 g Tryptophan 3-times per day for 2 weeks while continuing light therapy. The addition of Tryptophan resulted in a significant reduction in depression. 64% of the patients in this study showed very good clinical responses to the combined treatment with minimal side effects.1165 Dosage Notes Recommended dosage of Tryptophan is 500 – 1,000 mg per day for cognitive benefit or sleep. The University of Michigan Health Department recommends much higher doses for: • • • •

Lowering appetite and cravings: 500 mg – 2 grams per day Depression or Anxiety: 2 – 6 grams per day (with medical supervision) Chronic pain or migraines: 2 – 4 grams per day in divided doses (with medical supervision) Sleep disorders or insomnia: 500 mg – 1 gram before bedtime1166

Tryptophan is a precursor to the neurotransmitter serotonin in the brain. Tryptophan hydroxylase is the rate-limiting enzyme needed for serotonin production. And requires magnesium and Vitamin B6 to synthesize serotonin. Tryptophan is also a precursor to the synthesis of Vitamin B3 (niacin). So if you don’t have enough niacin in your body, supplementing with L-Tryptophan will not efficiently produce serotonin because it’s being used to produce niacin. Which also depletes stores of the vitamin cofactors B1, B2 and B6. So supplement L-Tryptophan with a B-Vitamin complex that includes Vitamins B3 and B6, and magnesium. Note that some of the clinical trials used in this post use much higher doses of Tryptophan. Which is not recommended and usually not necessary.

Too much Tryptophan will make you sleepy. And could produce excess levels of 5-HTP and serotonin which can lead to Serotonin Syndrome. Side Effects Tryptophan is a normal part of your diet and considered non-toxic and safe at recommended doses. But in the unlikely event that you already have adequate levels of Tryptophan in your body, supplementing with more could cause problems. As can dosing more that the recommended amount. Tryptophan could cause stomach upset, loss of appetite, nausea, heartburn, drowsiness, headaches, dry mouth and sexual problems. Start at the lowest dose to see how your body reacts. When first starting with L-Tryptophan take your dose in the evening to avoid possible drowsiness issues. Caution: Low to moderate doses of Tryptophan (30 mg per pound of body weight), or about 4.5 grams for the average 165 lb. adult is considered safe and free of side effects. However, most don’t need to dose at nearly these levels. DO NOT use L-Tryptophan if you are taking antidepressant medications including SSRI’s. Because these drugs delay normal degradation of serotonin in brain synapses leaving more serotonin circulating in your brain. Too much Tryptophan in combination with these drugs can produce Serotonin Syndrome which can lead to delirium, involuntary muscle contractions, high fever, and coma. And worse case and a very real scenario is death.1167 Available Forms L-Tryptophan is available in tablet and capsule form usually 500 – 1,000 mg. You also get Tryptophan in foods you eat including chocolate, oats, bananas, dried dates, milk, cottage cheese, meat, fish, turkey, and peanuts. Approximately 300 mg of Tryptophan is available in three ounces of turkey, lamb, beef, tuna, or peanuts. Fortunately, relative to other amino acids, small amounts are needed for a therapeutic effect. But there are all kinds of reasons why your body may not be making good use of the Tryptophan you’re getting from food. See “Tryptophan benefits” for more on why it may be a good idea for you add Tryptophan to your stack. Nootropics Expert® Recommendation Tryptophan 500 – 1,000 mg per day I recommend using Tryptophan as a nootropic supplement. Your body does get some Tryptophan from the food you eat. But this amino acid is competing with other amino acids for transport to your brain. It’s competing for the same receptors. And carbohydrates

vs. proteins in your meals can affect Tryptophan’s ability to synthesize serotonin in your brain. Supplementing with L-Tryptophan will make more of this amino acid available to synthesize serotonin and melatonin. L-Tryptophan is especially helpful for those with low serotonin levels. Boosting this crucial neurotransmitter can help alleviate insomnia, pain, depression and anxiety. Adding L-Tryptophan to your nootropic stack can also boost the neurotransmitters dopamine, norepinephrine and melatonin. Improving sleep, cognition, memory, mood and decision-making. Start with 500 mg of L-Tryptophan per day and take it in the evening. See how your body reacts and how you feel the next day. Increase the dose to no more than 2 grams per day as needed. And watch for side effects. L-Tryptophan requires adequate levels of Vitamin B3, B6 and magnesium for serotonin synthesis. So add a good B-Complex vitamin and magnesium to your stack when using L-Tryptophan.

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Turmeric Turmeric has been shown to increase Brain-Derived Neurotrophic Factor, fight depression, improve cognition, focus and libido, and protect the brain from inflammation Turmeric (Curcuma longa) is one of the most powerful natural remedies in Ayurvedic and Chinese medicine. This ancient herbal remedy has been used for at least 6,000 years.1168 It is one of the most studied herbs in Ayurvedic, Siddha, Unani and Chinese healing. Turmeric has remarkable nootropic properties. And stands far above many modern medicines used to treat neurodegenerative diseases like depression, Alzheimer’s and stroke. Turmeric is a perennial shrub native to southern Asia. It is a member of the ginger family (Zingiberaceae). And the Chinese name, jianghuang, literally means “yellow ginger.” Most of the turmeric we get is grown in India. But turmeric is also cultivated in China, Taiwan, Japan, Myanmar (Burma), Indonesia and throughout Africa. The major constituent of turmeric is curcumin (diferuloylmethane), which constitutes up to 90% of total curcuminoid content, with desmethoxycurcumin and bisdemethoxycurcumin comprising the remainder. Turmeric is used extensively in several countries as part of their system of national medicine. Turmeric is listed in the official Ayurvedic Pharmacopoeia of India. In the Pharmacopoeia of the People’s Republic of China. In the Japanese Herbal Medicines Codex. In Germany, turmeric is listed in the Drug Codex, approved in the Commission E monographs, and in the form of tea in the official German Standard License monographs. Curcumin and turmeric have been extensively researched for their anti-tumor, antioxidant, antiinflammatory and analgesic (pain-relieving) properties. In fact, a search of the U.S. PubMed database for research on turmeric returns 5,334 clinical trials on animals and humans.1169 And yet the National Center for Complementary and Integrative Health which is part of the same U.S. National Institutes of Health has this to say about turmeric: “There is little reliable evidence to support the use of turmeric for any health condition because few clinical trials have been conducted.”1170 That statement by an official medical resource in the USA tells you something about the American health care system. And its view of alternative medicines. And why books like “Head First” and websites like Nootropics Expert are so important for our nootropics community. So we can make our own decisions on how to boost our cognitive health. Turmeric, also known as “Indian Saffron”, has been used for thousands of years in traditional South Asian cuisine, and is the basic ingredient in curry. One recent study with 1,010 elderly Asian subjects found that those who ate curry “often” or “very

often” had significantly higher cognitive performance.1171 Turmeric has potent antidepressant qualities. And has been found to be more potent than the antidepressant Prozac. Researchers think Turmeric works by reducing the stress hormone cortisol while increasing levels of the neurotransmitter serotonin. Turmeric’s main active component curcumin provides protection against Alzheimer’s, major depression, epilepsy, and other neurodegenerative disorders. Scientists believe that much of this protective action comes from curcumin’s anti-inflammatory and antioxidant properties. Curcumin modulates neurotransmitter levels in your brain. And on a molecular level is a potent inhibitor of reactive astrocyte expression which prevents apoptosis (cell death) in your brain.1172 How does Turmeric Work in the Brain? Turmeric boosts brain health and function in several ways. But two in particular stand out. 1. Turmeric enhances neuroplasticity. Brain-Derived Neurotrophic Factor (BDNF) is a growth hormone responsible for the creation of new neurons (neurogenesis) in your brain. Higher levels of BDNF can increase mood, intelligence, memory and productivity. And can reduce risks for neurodegenerative diseases like Alzheimer’s and Parkinson’s. Using turmeric or its active compound curcumin can boost your intelligence and memory. And can elevate your mood especially if you’re prone to depression. Several studies have shown that turmeric or its active component curcumin significantly boosts BDNF.1173 Researchers found that curcumin activated extracellular signal-regulated kinases (ERKs) and p38 kinases, cellular signal transduction pathways known to be involved in the regulation of neuronal plasticity and stress responses. Administration of curcumin to mice in this study increased the number of newly generated cells in the hippocampus. Showing that curcumin enhances hippocampus neurogenesis. And that curcumin activity in the brain enhances neuroplasticity and repair of brain cells.1174 Another study using the turmeric volatile oil Ar-turmerone showed this compound also supported regeneration of brain cells. Scientists discovered that when neural stem cells were bathed in Arturmerone, up to 80% more stem cells grew into neurons or other cells. Scientists then injected this turmeric extract into a part of rat’s brains where these cells are located. And witnessed a similar increase in growth of stem cells into neurons.1175 2. Turmeric boosts dopamine and serotonin levels in the brain. These are the ‘feel good’ neurotransmitters in your brain. Turmeric and its active compound curcumin has been studied and used effectively as an anti-depressant for centuries. Researchers in India set out to establish how curcumin worked in the brain to provide this antidepressant action. In this study they investigated both curcumin and its ability to boost mood as well

as the effect of Piperine as a bioavailability enhancer. The scientists found that curcumin increased serotonin and dopamine levels in the brain. And inhibited monoamine oxidase enzymes (both MAO-A and MAO-B) just like popular prescription antidepressant MAOI’s. Curcumin even enhanced the effectiveness of popular SSRI antidepressants Prozac, Effexor, and Zyban. The team found no increase in norepinephrine when using curcumin to boost neurotransmitters. Avoiding the irritability and other symptoms of an over-amped fight-or-flight response. And the scientists found that stacking curcumin with Piperine significantly boosted bioavailability. They concluded that curcumin combined with Piperine was a “potent natural antidepressant approach to managing depression”.1176 How things go bad Chronic stress, anxiety and free radicals (oxidation) damage your brain. This damage can manifest in several ways including memory loss, brain fog, anxiety, depression, and even neurodegenerative diseases like Alzheimer’s and Parkinson’s. ↓ Chronic stress reduces memory ↓ Toxins kill brain cells ↓ Free radicals destroy neurons and synapses ↓ Serotonin and dopamine decline ↓ Brain-Derived Neurotrophic Factor declines Under conditions of chronic stress or depression your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition and decision-making all suffer as a result. Turmeric benefits A member of the ginger family of herbs, turmeric is the seasoning that gives curry powder its yellow color. It’s long been known for its anti-inflammatory and antioxidant properties. And is actively studied today for applications as a nootropic. Turmeric or anyone of its several active compounds including curcumin and Ar-turmerone undoes damage to your brain caused by depression or chronic stress. Turmeric and curcumin boost neuron regrowth (neurogenesis), increases dendrites, repairs DNA, reduces inflammation, counters free radical damage, and boosts neurotransmitters. Turmeric inhibits monoamine oxidase enzymes (both MAO-A and MAO-B) just like popular prescription antidepressant SSRI’s and MAOI’s. Research shows that curcumin or turmeric can boost the effects of some popular antidepressants.

Boosting the ‘feel-good’ neurotransmitters serotonin and dopamine can alleviate depression, improve mood, boost alertness, cognition, decision-making, memory and even libido. Curcumin, the most active component of turmeric, activates genes to produce a huge array of antioxidants that serve to protect your mitochondria. Curcumin also improves glucose metabolism, which is great for maintaining a healthy balance of gut bacteria. This critical microbiome in your gut directly influences how well your brain functions. How does Turmeric feel? Curcumin is the main active component of turmeric. So most of the positive reviews and studies have been conducted using curcumin. Curcumin is known to possess antimicrobial, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, anti-tumor, anti-cancer, anti-phlogistic, anti-diabetic, anti-psoriasis, anti-thrombotic, anti-hepatotoxic and a host of other useful properties. If you are in perfect physical and mental health, you may not feel the effects of supplementing with turmeric or curcumin. Turmeric’s neuroprotective qualities may not be felt if your brain is in perfect working order. But the effects of long-term supplementation will help you ward off diseases like Alzheimer’s and Parkinson’s. The most frequent comment from supplementing with turmeric comes from those dealing with chronic pain. Turmeric relieves the pain of osteoarthritis and fibromyalgia. Chronic pain usually results in insomnia or poor sleep quality, loss of memory, depression, and other stress-related symptoms. Adding curcumin or turmeric to your nootropic stack can help relieve chronic pain. You’ll sleep better and feel more alert the next day. Supplementing with turmeric or curcumin improves attention, working memory, and mood. And is reported to relieve the symptoms of migraine headaches. The Research Eat Your Curry Curcumin, from the curry spice turmeric, has been shown to have antioxidant and anti-inflammatory properties. And can reduce beta-amyloid plaques that are associated with Alzheimer’s Disease. But scientists were not satisfied with the evidence of turmeric’s benefits in real life. So in 2003, a research team in Singapore recruited 1,010 non-demented elderly Asian people aged 60 – 93 years. The authors of the study compared Mini-Mental State Examination (MMSE) scores for three categories and regular curry consumption. The scientist found that those who consumed curry “occasionally” and “often or very often” had much higher MMSE scores than those who “never or rarely” consumed curry. The study authors reported that regular curry consumption was evidence of better cognitive

performance. The bottom-line → eat your curry.1177 Turmeric as an anti-depressant A study conducted in India looked at the efficacy and safety of using curcumin, one of the active ingredients found in turmeric, for treating major depression. 60 patients diagnosed with major depressive disorder were chosen to receive either 20 mg of fluoxetine (Prozac), 1000 mg of curcumin, or a combination of both daily for 6 weeks. The study found that the best response (77.8%) was with the group of patients treated with a combination of curcumin and Prozac. The Prozac-only group experienced a 64.7% improvement in depression symptoms. And the curcumin-only group came in at 62.5%. The researchers concluded that curcumin could be used as an effective and safe treatment for patients with major depression.1178 Curcumin Reduces Stress Turmeric has long been used in traditional Chinese medicine to manage stress and depression-related disorders. Scientists had already figured out turmeric’s antidepressant effects in animal and human studies. So they imagined that curcumin may also alleviate stress caused by HPA (hypothalamicpituitary-adrenal) dysfunction. For this study the scientists used rats. They subjected the animals to stress for 20 days by putting them through several tasks known to stress a rat. Putting rats through this unfortunate (for the rats) series of events produced the kind of symptoms you would see in humans subjected to ongoing, chronic stress. The rats had abnormal adrenal gland weight, increased thickness in the adrenal cortex, elevated cortisol levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by giving the rats curcumin in their food. The research team also found that chronic stress down-regulated BDNF levels and reduced the ratio of cAMP to CREB levels in the hippocampus and frontal cortex of the rats. Giving the rats curcumin blocked all these stress-induced physical responses in their brains. The scientists concluded that these results provided compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, could be related to the modulating effects of curcumin on the HPA axis and neurotrophin expressions.1179 Dosage Notes You cannot get the immediate therapeutic and nootropic benefits of turmeric by simply eating more curry. Or adding turmeric to your food. Turmeric root contains only about 3% curcumin. The most convenient way to start experiencing the benefits of turmeric is to get a high quality, 100% organic turmeric extract that contains at least 95% curcuminoids.

But curcumin and turmeric on their own are poorly absorbed by your gut. You must boost the bioavailability and absorption of this potent nootropic. And the most efficient way to boost bioavailability is to combine turmeric or curcumin with Piperine. One study showed combining curcumin with 20 mg of Piperine increased bioavailability by 2000%!1180 Turmeric is fat-soluble so you must take it with a high quality fat for maximum absorption. You can use unrefined coconut or extra virgin olive oil. Standardized turmeric or turmeric extract (95% curcuminoids) 750 mg 3-times per day. Turmeric liquid extract (1:1) 30 – 90 drops per day. Tincture (1:2) 15 – 30 drops 4-times per day. Dried turmeric root powder 2.5 – 4 grams per day. Side Effects Turmeric is natural and considered non-toxic and safe when taken at recommended doses. Taking large amounts of turmeric for extended periods can cause stomach upset, and possibly ulcers. If you have gallstones or a bile passage obstruction you should not supplement with turmeric. Turmeric may lower blood sugar levels which could be a problem for diabetics. Pregnant and breastfeeding women should not supplement with turmeric. And because turmeric can act as a blood thinner, stop supplementing with turmeric 2 weeks before surgery. Turmeric can also strengthen the effects of blood thinning medications. Available Forms Turmeric is available as a powder, tablets, capsules, tincture, and tea. And is preferred over curcumin if you’re using it for inflammatory conditions like arthritis, tendonitis, or an autoimmune condition. Curcumin is a natural chemical found in and extracted from turmeric. Several companies have developed their own version of this powerful nootropic. Sabinsa’s Curcumin C3 Complex® boasts the most clinical studies of any of the patented forms of curcumin. This curcumin product is standardized to 95% Curcuminoids. Sabinsa also produces the standardized Piperine extract called BioPerine®. And supplement makers who feature Curcumin C3 Complex® from Sabinsa also typically include BioPerine® in their formula. BCM95® by DolCas Biotech is a standardized extract of turmeric containing curcumin-essential oil complex of 86% curcuminoids and 7-9% essential oils. As far as I can tell this is the only extract that includes turmeric volatile oils which is important to cognitive health. Recall from earlier in this article that turmeric volatile oil Ar-turmerone supported regeneration of brain cells

Longvida® is a standardized curcumin extract that the company claims is at least 67-285 times more bioavailable than standard 95% curcumin. But does not contain any of the volatile oils found in natural turmeric. One study showed that this extract increases synapses in mice.1181 Another study in humans showed Longvida® significantly improved attention, working memory, and mood compared to placebo.1182 Meriva® is another patented form of curcumin combined with soy lecithin. The two compounds are a 1:2 ratio with microcrystalline cellulose added. The company claims that the addition of soy lecithin improves bioavailability of curcumin. Total curcumin in each capsule is 20%. Much higher doses of this curcumin extract are needed for optimizing cognition. And is primarily targeted at bone, joint, eye and skin health. Active ingredients of Turmeric include curcuminoids and volatile oils. Look for the percentage of active ingredients listed on the bottle or package. Your best option is choosing a standardized extract of at least 95% curcuminoids. Unless the supplement contains a patented compound from the companies listed above, you can assume that the extract has been processed using toxic solvents to extract curcumin from turmeric (not good). And avoid supplements that list “other ingredients” on the label. Look for Certified Organic to ensure the root used to make your Turmeric supplement is free of heavy metals, pesticides and herbicides. Nootropics Expert® Recommendation Turmeric Extract (95% curcuminoids) 750 mg 3-times per day I recommend using Turmeric or Curcumin as a nootropic supplement. Your body does not make Turmeric on its own. So to get its benefits you must take it as a supplement. Turmeric is the anti-Alzheimer’s spice. Studies show that in parts of India where curries are eaten most often, Alzheimer’s disease is extremely rare. Turmeric is especially helpful for those suffering from depression or chronic pain. Turmeric has a combination of curcuminoids, volatile oils and proteins that make it anti-bacterial, anticancer, anti-inflammatory, and anti-septic. Some neurohackers maintain that turmeric or curcumin is the best nootropic. You can increase the bioavailability of turmeric by combining it with Piperine (black pepper extract) and a healthy fat like olive or coconut oil. You can safely take up to 3,000 mg of Turmeric extract daily if needed. Most get all the benefit they need with 750 mg. Dosed 3-times per day.

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Tyrosine Tyrosine enhances working memory, executive function, creative flow states, stress reduction, better mood, anti-anxiety and lessens symptoms of ADHD L-Tyrosine is the master precursor required to form all catecholamine neurotransmitters. Your brain converts L-Tyrosine to L-DOPA which then produces the neurotransmitter dopamine. The unused dopamine is then further converted into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). This triad of neurotransmitters are collectively referred to as “catecholamines”. “Tyrosine” is derived from the Greek word tyros, meaning cheese. It was first discovered by German chemist Justus von Liebig in 1846 in the protein casein from cheese. Tyrosine is considered a non-essential amino acid because it can be synthesized in your body from phenylalanine. Which is found in many high-protein foods such as poultry, fish, dairy, nuts, soy products, lima beans, avocados, and bananas. L-Tyrosine enhances working memory and executive function in the prefrontal cortex. It helps with creative flow states, is fuel for inspiration, cognitive flexibility, and the kind of “convergent thinking” you do in multiple choice exams. L-Tyrosine assists in the production of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) which are crucial in maintaining both overall physical and cognitive health. L-Tyrosine vs N-Acetyl L-Tyrosine (NALT): What’s the Difference? N-Acetyl L-Tyrosine (NALT) is the amino acid L-Tyrosine with an acetyl group added. When you take NALT as a supplement, it breaks down in your kidneys back into L-Tyrosine. So in theory, the two supplements offer the same benefits. There is some debate in the nootropics community on which is more effective. NALT or plain LTyrosine. NALT is a more soluble form of L-Tyrosine so it should be more bioavailable to your body. However, some studies report that in some cases, a sizeable percentage of supplemental NALT is excreted in urine before it’s converted into L-Tyrosine.1183 On a personal note, I haven’t had any issues using NALT as a source of L-Tyrosine. It gives me a dopamine and adrenal boost you’d expect from supplementing with a dopamine precursor. But when I haven’t any NALT around I successfully switch to L-Tyrosine although at a slightly higher dose. When dealing with ADHD/ADD, L-Tyrosine is particularly effective when stacked with ALCAR (Acetyl-L-Carnitine) and CDP-Choline. They both easily crosses the blood-brain barrier for boosting

acetylcholine levels. And seems to positively influence serotonin levels. And Tyrosine provides my brain with the dopamine it needs to mitigate symptoms of ADHD/ADD. I find that L-Tyrosine stacked with 20 mg of Ritalin twice a day works particularly well. Clearly, this brain doesn’t have the capacity to produce enough dopamine on its own. And needs the boost that comes from supplementing with Tyrosine. So like all nootropics, YMMV. Always consider how each nootropic works synergistically with others in your stack. And how they work with any meds you need to take. This is as much art as it is science. And experimentation is key for optimal cognition. How does L-Tyrosine work in the Brain? L-Tyrosine boosts brain health and function in several ways. But two in particular stand out. 1. L-Tyrosine improves memory and cognition under acute stress. Acute stress is defined as short-term stressors that can affect cognition. Examples are extreme heat or cold. Things like cold showers, extreme sports, car accidents, relationship problems, intense movies, business deals gone awry, exams and war zones. In one study done at the University of Bedfordshire in the UK, the effect of L-Tyrosine on cognitive performance was measured before an exercise task. Researchers recruited 8 soccer players. And had them complete a 90-minute soccer simulation performance test in an environmental chamber set at 77 degrees Fahrenheit. The soccer players were given either L-Tyrosine before exercise or a placebo. Cognitive performance was measured before the exercise task. Then again at “half-time”, following half time, and following the entire simulation. The cognitive performance task assessed dual-task and vigilance. The outcome revealed that cognitive vigilance and reaction time among soccer players significantly improved following administration of LTyrosine. Results showed that in warm-weather conditions, L-Tyrosine could enhance cognitive function and prevent cognitive impairment during exposure to exercise-heat stress.1184 2. L-Tyrosine boosts neurotransmitters. L-Tyrosine taken as a supplement converts into the neurotransmitter dopamine. Dopamine helps control movement in your body, is fundamental to memory, attention and problem solving. The unused dopamine can then convert into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Norepinephrine is important for attentiveness, emotions, sleeping, dreaming, and learning. Epinephrine drives your ‘flight-or-flight’ response. It’s what prompts your reaction to dangerous

circumstances, emergency situations, or in stressful situations or environments. In one study done in the Netherlands, researchers determined if L-Tyrosine would boost cognitive resources associated with cognitive control. They performed tests designed to measure “working memory” using the N-Back Test. Study participants were assigned to engage in a “1-back” condition of easy difficulty and then a 2-back condition of tougher difficulty. Those that used L-Tyrosine demonstrated superior performance in the 2back test, but not the 1-back test. The study authors suggested that L-Tyrosine provides greater cognitive enhancement when cognitive demand increases. The bottom-line; supplementation of L-Tyrosine may help you increase your IQ score due to maximizing catecholamine reserves.1185 How things go bad As we get older, our brain and body chemistry and energy metabolism changes. ↓ Dopaminergic neurons are damaged or die ↓ Neurotransmitter levels decline ↓ Thyroid hormones decline ↑ Stress levels increase ↓ Working memory and mood decline All of these changes are often attributed to aging. But could be a result of dietary and lifestyle choices. Unchecked, they could lead to neurodegenerative diseases like Parkinson’s, a drop-in quality of life and depression. L-Tyrosine benefits L-Tyrosine can boost levels of the neurotransmitters dopamine, norepinephrine, and epinephrine. And contributes to the production of thyroid hormones T4 and T3. Tyrosine can help boost cognition especially in stressful situations. It helps improve decision making, ‘flow state’ and creativity, cognitive flexibility, and working memory. L-Tyrosine converts into L-DOPA to produce dopamine. L-DOPA is also used to make melanin in your body. This conversion process helps in the removal of neurotoxic quinones. And chelates heavy metals like mercury and lead which can accumulate in and damage neurons. The dopamine that is not used by your brain is available to produce norepinephrine (noradrenaline) which is important for attentiveness, emotions, sleeping, dreaming, and learning.

L-Tyrosine can be an effective nootropic when stacked with ADHD/ADD meds like Ritalin or Adderall. It helps supply extracellular dopamine needed to improve the effectiveness of stimulants used to boost the uptake of dopamine in your brain. How does L-Tyrosine feel? Keep in mind that L-Tyrosine is a precursor to catecholamines. So if you’re not ‘low’ on dopamine, norepinephrine, or epinephrine – you may not ‘feel’ anything. Many neurohackers report a lift in mood, better focus, concentration, increased energy, and an overall sense of well-being. L-Tyrosine can help readjust your motivation levels. It can help lower anxiety levels, especially social anxiety. Supplementing with L-Tyrosine can help bring your blood pressure down if its elevated from a stressful situation or environment. Take it before the stressful event if you can. L-Tyrosine helps buffer the effects of stimulants like caffeine or amphetamines. It helps potentiate and prolong the effects of Ritalin or Adderall and reduces the crash. If you’re into athletics or do manual work, you’ll find that supplementing with L-Tyrosine before a workout or construction job will leave you feeling great afterwards. It helps mitigate many of the effects of acute stress caused by short-term stressors. And L-Tyrosine helps your body to produce melanin, so you may find it easier to get a tan while at the beach. L-Tyrosine Research L-Tyrosine to treat ADHD Several studies have investigated using L-Tyrosine for the treatment of ADHD. One informal study published in the 1980’s determined that L-Tyrosine resulted in short-term relief from ADHD symptoms. But subjects eventually reached tolerance and a diminished effect. This is important for neurohackers to keep in mind. It seems that L-Tyrosine on its own can benefit some more than others. Regardless of if you’re treating ADHD or are perfectly cognitively healthy. I’ve seen more than one report of nootropic users experiencing tolerance after just a week of supplementing with L-Tyrosine. But most peer-reviewed, published studies show positive results. One study published in Neuropsychiatric Disease and Treatment in 2011 looked at using amino acid precursors for the treatment of ADHD. Including L-Tyrosine for dopamine, and 5-HTP for serotonin. The study used 85 young people aged 4 – 18 years old, all with a clinical diagnosis of ADHD. They were treated for an initial period of 8 – 10 weeks. Urinary samples to determine serotonin and dopamine levels were collected within the first 4 weeks. If they didn’t reach adequate levels, subjects were moved to higher dosing levels 2 and then 3 until they got relief from symptoms.

Researchers found that the dopamine and serotonin precursors yielded similar results to Strattera and Ritalin. And “the amino acid protocol may be equal in efficacy to potent, pharmaceutical ADHD medications”.1186 L-Tyrosine reduces blood pressure under stress This study is particularly interesting for its nootropic application. It’s commonly understood that blood pressure rises when we’re under stress. The source of stress doesn’t really matter. Stress up = blood pressure up. A study in Amsterdam showed that L-Tyrosine administration decreased blood pressure about 15 minutes after ingestion. This study involved assessing task performance following acute stress. Acute stress is usually short-term and can be caused by driving, fighting, athletics, martial arts training, war, combat training, CrossFit, cold showers, loud music, intense movies, loud noises, business deals, relationships, school, exams and more. The point is this study is applicable to every one of us. The study found that L-Tyrosine reduced diastolic blood pressure within 15 minutes of taking the supplement. And blood pressure normalized within 1 hour. This study tells us that L-Tyrosine may promote a decrease in blood pressure caused by stress. And could be used to mitigate the effects of stressful situations if taken prior to the stressful event.1187 L-Tyrosine promotes cognitive flexibility Cognitive flexibility applies to those who can adjust their thinking quickly to adapt to novel situations and stimuli. A high degree of cognitive flexibility is associated with increased fluid intelligence, superior reading and comprehension, and a healthier brain. Recent research (2015) supports the idea that L-Tyrosine promotes cognitive flexibility. In this trial, researchers recruited 22 adults. And setup a double-blind, placebo-controlled study. All subjects were assigned a task switching procedure to measure their flexibility. The results showed that receiving L-Tyrosine supplementation increased cognitive flexibility compared to the placebo group. The researchers determined that “L-Tyrosine can facilitate cognitive flexibility by repleting cognitive resources”.1188 The team observed that increased cognitive flexibility was likely due to a boost in dopamine concentrations. They noted that L-Tyrosine enhanced usage of various cognitive resources. And one way to increase your cognitive flexibility would be to start supplementing with L-Tyrosine. It stands to reason that people who are close-minded, set it their ways, are resistant to change and can’t cope with unexpected stimuli or situations have “cognitive rigidity”. And it’s likely due to suboptimal dopamine levels.

L-Tyrosine Recommended Dosage L-Tyrosine suggested dosage for cognitive benefit is 500 mg – 2 grams per day. You may find your body responds to smaller doses. Or even more if you’re stacking it with stimulants like ADHD meds. Listen to your body and see how you react. If you find you do not experience the full benefit from L-Tyrosine, then try using it an hour before or two hours after a meal. Because L-Tyrosine taken as a supplement may compete with other amino acids in food for transport into your system. I personally stack 500 mg L-Tyrosine with my Ritalin dose twice per day. And a final dose of L-Tyrosine late afternoon to prevent a stimulant crash. NOTE: long-term use of L-Tyrosine can suppress serotonin. Symptoms include depression, fatigue or severe anxiety feeling much like a panic attack. You can easily counter this by supporting serotonin with a 250 – 500 mg L-Tryptophan about 60 mins. before bed. L-Tyrosine Side Effects L-Tyrosine is considered non-toxic and very safe. Most neurohackers don’t have any negative side effects from using L-Tyrosine. At higher doses there are reports of stomach issues and migraines. Migraine problems usually happen to those who already suffer from migraines. This may be an indication that your neurotransmitter levels are already optimal, and you don’t need to supplement with L-Tyrosine. L-Tyrosine can increase your thyroid hormones. So if you are hyperthyroid, you should use caution when supplementing with L-Tyrosine because it may change the way your thyroid meds work. And if you’re taking MAO inhibitors (MAOI’s) like selegiline, Azilect, Marplan or Nardil you should not use L-Tyrosine. MAOI’s work in your brain by blocking the enzyme monoamine oxidase. This enzyme normally removes excess dopamine. But when you block the enzyme, more dopamine is released. So using L-Tyrosine in combination with MAOIs could raise dopamine levels too high. Resulting in a rapid rise in blood pressure (hypertensive crisis). Causing severe headache, nausea and sweating, severe anxiety, rapid heartbeat, chest pain, vision changes, shortness of breath and confusion. A severe increase in blood pressure from this combo can lead to hemorrhagic stroke or a heart attack. Where to buy L-Tyrosine L-Tyrosine is available to buy in powder, capsule, and tablet form. Capsules and tablets are usually 300 – 500 mg. Some pre-made nootropic stacks and workout stacks also include L-Tyrosine as part of their formula.

N-Acetyl L-Tyrosine (NALT) is an alternative to regular L-Tyrosine. NALT has an acetyl group added to L-Tyrosine in an attempt to make it more bioavailable. Ensure you read labels carefully and stick with manufacturers who follow Good Manufacturing Practices (GMP). And are GMP-Certified. And do your best to avoid toxic “other ingredients” which are usually listed at the bottom of “Supplement Facts” labels. Nootropics Expert® Recommendation L-Tyrosine 500 mg 2 or 3-times per day I recommend using L-Tyrosine as a nootropic supplement. Your body does synthesize some L-Tyrosine from phenylalanine which comes from high-protein foods like chicken, fish, almonds, avocados, and bananas. But most of us don’t get enough L-Tyrosine from our diet. So supplementation will help. L-Tyrosine is helpful for most neurohackers to combat stress and sleep deprivation. It’ll boost dopamine, norepinephrine, and epinephrine levels. It’s particularly helpful if you take L-Tyrosine prior to a stressful situation, workout, or physically demanding job. L-Tyrosine is especially helpful to those dealing with ADHD/ADD. It’s a great compliment to stack with stimulant meds like Ritalin or Adderall. L-Tyrosine will provide the dopamine your brain needs. It will help smooth out and prolong the effects of stimulant meds. And help prevent the associated crash when they wear off. A good stack for ADHD each time you are using your usual med dose is L-Tyrosine 500 mg, Alpha GPC, or CDP-Choline 300 mg, and ALCAR 500 mg. You can safely use up to 2,000 mg of L-Tyrosine per day when stacking with ADHD meds. But in smaller divided doses throughout your day.

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Uridine Monophosphate Uridine Monophosphate has been shown to increase neuron and synapse density, dopamine and acetylcholine release, boost learning and memory, and decrease depression Uridine Monophosphate (UMP or 5′-uridylic acid) is a pyrimidine nucleoside found in all living organisms ranging from humans to bacteria. Uridine is one of 4 repeating units that make up RNA (Ribonucleic Acid). RNA and DNA (deoxyribonucleic acid) are the main information carrying molecules in each of your cells. Uridine is so important to brain development, that it is included in human baby formulas.1189 RNA works as a messenger molecule, carrying the blueprint provided by DNA to tiny cellular factories called ribosomes. Ribosomes are in charge of protein synthesis and use the blueprint sent over from DNA by RNA to produce the right protein for the job required. Uridine is essential for optimized cognition and memory throughout your life. When taken as a nootropic supplement, Uridine Monophosphate easily crosses the blood-brain barrier.1190 UMP has much better bioavailability than dietary sources of uridine. CDP-Choline levels are increased once uridine reaches your brain. CDP-Choline is required for the synthesis of phosphatidylcholine (PC). PC in turn is a precursor of the essential neurotransmitter acetylcholine (ACh). Increased levels of PC and acetylcholine improves cognitive function. Uridine is also a major building block for the synthesis of neurons and synapses. And uridine enhances the growth of dendrites, which are projections from neurons that facilitate connections with other neurons.1191 The bottom line is that without uridine to make up RNA, DNA couldn’t get the info out for proteins to be synthesized. And life as we know it would cease to exist. Our bodies create some uridine. And we get uridine from the RNA of foods we eat including beets, beer, broccoli, fish, mushrooms, oats, parsley, sugar cane, tomatoes, and brewer’s yeast. Beer provides some of the highest uridine content of all the foods tested. The problem is most of the uridine we get from food never makes it from our digestive system to our brain. So we need to supplement with uridine monophosphate (UMP) to experience the benefits of uridine. Uridine does much more than merely act as a building block of RNA. Uridine acts in the formation of neurotransmitters, and the creation of new synapses. Adding uridine monophosphate to your nootropic stack can help improve alertness, focus, memory, learning ability and mood. Researchers have found that Uridine Monophosphate alone can improve memory. But stacking UMP with DHA (Omega-3) and choline works in synergy, increasing the number of synapses. Resulting in

improved cognition.1192 How does Uridine Monophosphate Work in the Brain? Uridine Monophosphate boosts brain health and function in several ways. But two in particular stand out. 1. Uridine improves memory. Uridine helps boost learning and memory in several ways. Uridine helps the growth of new synapses in your brain, increases signaling between neurons, and assists in the formation of acetylcholine (ACh). Memory is largely dependent on neuroplasticity which is associated with the ability to learn and form memories. This process of turning experiences into memories relies on the growth of new neurons (neurogenesis), new synapses (synaptogenesis), dendrite formation, and network reorganization. New neurons (neurogenesis) are encased in a phospholipid layer made up partly of phosphatidylcholine (PC). PC is made from CDP-Choline which is produced with the help of uridine.1193 Supplementing with uridine gives your brain the ability to create more phospholipids by providing an abundance of CDP-Choline. Resulting in new and stronger neurons. Uridine is a precursor to the formation of CDP-Choline which is a precursor to the formation phosphatidylcholine (PC). PC separates into choline and sphingomyelin in your brain. Choline is then available to form acetylcholine (ACh). Optimal ACh levels is crucial for cognitive performance.1194 Uridine also helps increase synapse formation (synaptogenesis) by enhancing neurite growth. Uridine signals this outgrowth by activating the P2Y2 receptor which controls neuron differentiation and synaptic protein synthesis.1195 2. Uridine impacts mood. Uridine stimulates the release of the ‘feel-good’ neurotransmitter dopamine in your brain. Phospholipids like phosphatidylcholine (PC) are required for cellular growth and repair, and specifically for synaptic function. PC synthesis is controlled by levels of its precursor CDP-Choline which is produced from cytidine triphosphate (CTP) and phosphocholine. Researchers found that supplementing with uridine monophosphate boosted levels of CDP-Choline. By promoting the synthesis of uridine triphosphate (UTP), which was partly converted to CTP. Uridine also enhanced neurite outgrowth with the help of nerve growth factor (NGF). The research team found that dopamine release correlated with neurite outgrowth influenced by UMP.1196 Increased levels of dopamine has a significant effect on mood, learning and attention. How things go bad Uridine levels decline as we age. And if you were not breast-fed as a baby, you started life at a deficit. Breast milk provides the uridine required for optimal brain growth.

↓ Cognition, memory, recall, reaction time and mood diminish ↓ Brain cell membranes degenerate ↓ Neurotransmitter levels decline ↓ Neurons and synapses decline All of these changes in brain energy metabolism are contributing factors to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, ALS, epilepsy, and dementia. But even if you’re not concerned with age-related cognitive decline, or the effects of aging, Uridine Monophosphate can help. Uridine Monophosphate benefits Uridine plays a critical role in the pyrimidine metabolism in your brain.1197 In the simplest terms, uridine monophosphate promotes neuron and synapse growth and DNA repair.1198 Benefits reported by neurohackers include uplifting and stabilizing mood, reducing stress and OCD symptoms, a reduction in anxiety, and modulating and normalizing dopamine release. Adding uridine monophosphate to your nootropic stack helps: • • • • • •

Reduce general cognitive decline Increase free phosphatidylcholine (PC) Increase acetylcholine in your brain Increase receptor (neurogenesis), and synapse (synaptogenesis) densities Improve cellular phospholipid membrane health Boost learning and memory

How does Uridine Monophosphate feel? Neurohackers report the effects of uridine monophosphate (UMP) supplementation is most pronounced when stacked with DHA or Omega-3’s. UMP elevates mood and relieves depression. Feelings of “well-being’ are enhanced. And verbal fluidity, memory and focus are all noticed at doses as low as 150 mg of UMP. Those dealing with ADHD report that uridine monophosphate increases cognition without causing anxiety or mood changes. This is backed up by science that shows uridine reduces the side effects associated with medication that effects dopamine and GABA neurotransmission.1199 Others report that uridine monophosphate helps bring clarity of thought, resolving problems is faster and easier, math is easier, and making decisions from a clear emotional state simplifies life. The common thread through most reviews on uridine monophosphate is greater success when stacking UMP with a choline like Alpha GPC and Omega-3’s. This synergy is backed up by multiple clinical trials.

The Research We have plenty of research on uridine monophosphate. But most of the studies and trials have been done using animals. Likely because uridine is naturally found in every cell of the human body. It’s a key element in a chain of four molecules that make up the RNA chain. And since uridine is a natural element, it cannot be patented. So very little money can be made by the large pharmaceutical companies since UMP can’t be sold as a “drug”. The clinical evidence that we do have for uridine monophosphate strongly suggests that it is a powerful and useful nootropic. Uridine Monophosphate Boosts Intelligence Consumption of certain nutrients can influence brain function even if you’re not trying to “fix a problem”. We know that supplemental DHA (Omega-3) can improve cognition in humans. DHA makes up 60% of your brain and is most prominent in the phospholipid membrane of each of your brain cells. Adding DHA to your nootropic stack has also been shown to increase the density of dendritic spines in the hippocampus which enhances synaptic transmission.1200 Researchers have found that supplemental Uridine Monophosphate (UMP) also promotes synthesis of synaptic phosphatides. But scientists found that taking DHA with UMP has an even greater effect on synthesis of synaptic phosphatides. Greater than taking each nootropic on its own. Scientists also found that combining DHA with UMP and choline amplifies increases in dendritic density in the hippocampus. In one very detailed study with gerbils, researchers found that the combination of DHA, UMP and choline significantly increased learning and memory in the young animals.1201 Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal said of this study, “Now that we know how to make gerbils smarter, it’s not too far a stretch to hope that people’s intelligence can also be improved. Quite frankly, this can’t happen soon enough, as every environmentalist, advocate of evolution and war opponent will attest.” The synergy of these three nootropics (DHA, UMP and choline) in boosting learning and memory are powerful motivation for any neurohacker to add these supplements to their stack. Uridine Monophosphate Fights Depression Research has confirmed the antidepressant effects of omega-3 fatty acids. Associate Professor of Psychiatry William A. Carlezon Jr. of Harvard also found that uridine, a compound found in sugar beets and molasses, has similar effects. And when both Omega-3 and uridine were used in combination, there were found to be effective at lower doses of each. Professor Carlezon speculated that the antidepressant effects of Omega-3 and uridine were caused by affecting fats in the brain. Making membranes more resilient eased the flow of neurotransmitters.

An imbalance of neurotransmitters is thought to be a cause of depression. To test this theory, the Professor and his colleagues put rats through a 15-minute swim test during which the animals eventually stopped trying to climb out of the water tank and became largely immobile. Just enough to keep their heads above water. After the test, the rats were dried off with a towel, placed in a warm enclosure for 30 minutes and then returned to their cages. The next day, rats were retested for 5 minutes each. And the rats that hadn’t received enough omega-3’s or uridine became motionless much more quickly. The researchers equate the onset of immobility in rats to depression in humans. The animals that received either Omega-3 or uridine, or lower doses of both, continued to swim around. Professor Carlezon said of the study, “They seem to be protected from the ability of stress to cause depression”. Adding Omega-3’s or uridine monophosphate to your stack can help you avoid depression. For an even more pronounced antidepressant effect, combine Omega-3’s with uridine monophosphate, but at lower doses of each.1202 Uridine Monophosphate May Help Prevent Alzheimer’s Alzheimer’s researchers agree that cognitive decline seen in Alzheimer’s patients is caused by loss of brain synapses. Researchers at MIT had a theory that restoring some of these synapses could provide an effective treatment for Alzheimer’s. An MIT team reported in Brain Research that rodents given a cocktail of DHA (Omega-3), uridine and choline showed a greatly increased concentration of dendritic spines. These dendritic spines receive messages in postsynaptic neurons. The head of the research team Professor Richard Wurtman said of the study that synapse regeneration had occurred. To Alzheimer’s researchers, this synapse regeneration was very unusual and came as a surprise. In this study, some of the rats received all three compounds (Omega-3, uridine, and choline), and some received only one. The improvements in synapse growth and cognitive ability were greatest in the rats given all three.1203 Other research ongoing for at least the last 10 years shows that early treatment using “diet” could significantly slow the progression of Alzheimer’s disease. The research suggests that supplementing with Omega-3’s, uridine monophosphate and choline may help you avoid Alzheimer’s altogether. Published in the Journal of Nutritional Biochemistry, a study from the University of Eastern Finland and conducted throughout Europe proved you could reduce dementia risk. And reduce amyloid accumulation in Alzheimer’s mouse models.

The results of this study showed that even slight changes in the composition of the diet may, under a sufficiently long period of time and at an early stage of the disease, lead to significant changes in brain metabolism and improved memory performance.1204 The supplements used in this study included uridine-monophosphate, phospholipids, B-vitamins, and antioxidants. This combination has been put into a new supplement called “Souvenaid” which is undergoing clinical trials in Europe and the United States. Dosage Notes Recommended dosage of Uridine Monophosphate (UMP) for nootropic benefit is 150 - 250 mg per day twice per day. I recommend taking UMP with a good multivitamin that includes the B-Vitamin group and a broad range of trace minerals including magnesium. For best results stack UMP with Omega-3’s that include at least 700 mg of DHA and 300 mg of EPA. Introduce a good choline source after a couple of weeks of supplementing with uridine monophosphate. Start with 50 mg of Alpha GPC or CDP Choline. And increase your dose depending on response to 300 mg. If you find that choline supplementation increases depression, stop using choline and try using ALCAR as an alternative. Everyone’s body chemistry is different. To find the optimal dose of uridine monophosphate for you will take patience and some experimentation. Too little UMP and you won’t see any benefit for a long time. Too much uridine and you’ll feel emotionally dull and/or overly focused. Side Effects Uridine is produced naturally in your body. So is considered well-tolerated and safe. Taking uridine monophosphate with food may help avoid any side effects. Neurohackers report only minor side effects like a decrease in emotions (feeling like a robot). But this has only been noted at very high doses of uridine monophosphate. If you do not respond well to B-Vitamins or SAM-e, you may not enjoy the benefits of UMP. Especially if you have problems with methylation. Available Forms Uridine Monophosphate (UMP) is available in capsule and powder form. UMP is water soluble and can be taken sublingually. Sublingual doses are reported to be up to 7 – 10-times the equivalent dose compared to taking UMP orally. Triacetyluridine (TAU) comes in capsules and is fat soluble. TAU is up to 4 -7-times stronger when

taken orally compared to UMP. Neurohackers report that UMP is more effective, and a better value that TAU. Nootropics Expert® Recommendation Uridine Monophosphate 150 - 250 mg twice per day I recommend using Uridine Monophosphate (UMP) as a nootropic supplement. Your body does make some uridine on its own. And you get uridine from the food you eat. But research has shown that your body does not retain enough of a usable form of uridine for cognitive benefit. Uridine Monophosphate is critical for the formation of RNA (ribonucleic acid). The main messenger molecule needed to transfer DNA’s blueprints for protein synthesis. Uridine is a precursor in the synthesis of CDP Choline. Which is a precursor to the synthesis of phosphatidylcholine (PC). PC is required for the synthesis of acetylcholine (ACh). Uridine enhances the release of the feel-good neurotransmitter dopamine. And uridine enhances the growth of neurons and synapses. Uridine Monophosphate is especially helpful if you’re dealing with stress or depression. I suggest a dose of 150 - 250 mg of UMP twice daily. It takes a while to feel the effects of uridine monophosphate. But you can amplify the effects of UMP by stacking it with 300 mg of Alpha GPC or CDP Choline and 700-1,000 mg of DHA (Omega-3). Do not push it by taking much more than the recommended dose of UMP. You may experience unwanted side effects.

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Valerian Valerian is known for its anti-anxiety and calming effects and promoting restful sleep. Valerian (Valeriana officinalis) is an herb native to Europe and northern Asia. And is now grown in England, Holland, and the USA for nootropic supplement manufacturers. Valeriana officinalis belongs to the Valerianaceae family of plants which includes as many as 250 different types. Many are referred to as “Valerian”. Valeriana officinalis is the species used in Europe and the USA. Valerian edulis is used in Mexico and Valerian wallichii is used in India. V. edulis contains substantially higher concentrations of valepotriates (up to 8%). Here we are investigating the nootropic benefits of the most widely used Valerian supplement in the West; Valeriana officinalis.1205 The medicinal part of the plant used in nootropic supplements is the root or rhizome. The sedative effects of Valerian were first mentioned by Hippocrates several thousand years ago. And have since been confirmed in clinical trials by modern medicine. Valerian likely got its name from the Latin word valere meaning to be healthy or strong. The Greek physician Galen used Valerian for treating epilepsy and insomnia. It’s modern usage likely got its start in 1567 by Italian nobleman Fabio Colonna, who suffered from epilepsy. He found Galen’s reference and claimed it completely restored his health.1206 Valeriana officinalis contains over 150 compounds. But those identified of clinical importance are valepotriates, and their breakdown products baldrinals, valerenic acid, Valerenal, and valeranone.1207 Valerian also contains the amino acids arginine, GABA, tyrosine, and glutamine. As a nootropic, Valerian is used primarily to lower stress and promote a good night’s sleep. How does Valerian work in the brain? Valerian boosts brain health and function in several ways. But two in particular stand out. 1. Valerian improves sleep. Valerian is the most commonly used herbal nootropic to induce sleep in the USA and Europe. Research continues to establish accurately why this supplement works to help sleep. But so far, science has determined that the compounds valerenic acid and bornyl acetate found in Valerian account for its sleep-inducing qualities. These compounds inhibit the breakdown of GABA in the brain resulting in sedation. And the aqueous extracts (water-based) of Valerian roots contain significant amounts of GABA which could directly cause sedation.1208

Researchers at the University of California in San Francisco did a systematic review of all the sleep using Valerian studies they could find. To find out if Valerian really did improve sleep like everyone said it does. The team found 16 randomized, controlled trials totaling 1,093 patients that satisfied their criteria. Doses ranged from 225 to 1,215 mg of Valerian per day. Only 2 studies stated that the herb was standardized to a specific amount of valerenic acid. But the evidence overall was clear. Valerian is a more attractive option to other sleep agents because of the lack of a ‘hangover effect’ the next day. And overall, patients got to sleep faster and had better quality sleep.1209 2. Valerian reduces stress. A natural alternative to benzodiazepines, Valerian helps reduce anxiety. And helps you cope with stress. GABA is the primary inhibitory neurotransmitter known to counterbalance the excitatory neurotransmitter glutamate. And research shows that often, those suffering from anxiety disorders are dealing with a dysfunctional GABA system.1210 Of all the studies demonstrating Valerian’s ability to help control anxiety and stress is best shown in the following study. One of the most stressful and painful procedures in female medicine is hysterosalpingography. This procedure evaluates the uterine cavity and fallopian tubes and is typically performed on infertile women. In this study, 64 infertile women undergoing hysterosalpingography (HSG) were given a single dose of 1,500 mg Valeric capsules 90 minutes before starting the procedure. Valerenic acid is one of the active compounds found in Valerian. Anxiety severity was measured before and then again 90 minutes after the procedure. The researchers concluded that Valerenic acid (Valerian) significantly reduces anxiety in women undergoing HSG.1211 How things go bad Chronic stress, anxiety, poor blood flow and free radicals (oxidation) can damage your brain. And one of the ways this manifests is memory loss. It comes as no surprise that people with memory loss experience higher rates of anxiety and depression. As verified in one Australian research study.1212 ↓ Chronic stress reduces memory capacity ↓ Toxins kill brain cells from the inside ↓ Free radicals destroy neurons and synapses ↓ Neurotransmitter levels decline

↓ Brain-derived neurotrophic factor (BDNF) declines Under conditions of chronic anxiety your brain loses the capacity to transmit signals between neurons efficiently. Memory, cognition, and decision-making all suffer as a result. Valerian benefits Valerian extract helps relieve anxiety. The valerenic acid and valerenol in Valerian binds to GABAA receptors which provides its anxiolytic effect. Like the prescription drugs Xanax and Valium but without the side effects associated with these pharmaceuticals.1213 Studies show that valerenic acid also modulates serotonin and norepinephrine in the hippocampus and amygdala regions of your brain. Also providing an anti-anxiety effect.1214 Valerian helps reduce the time it takes you to fall asleep. And provides a better night’s sleep. One Swedish study showed Valerian provided ‘perfect’ sleep for 49% of the people in the study. And 89% reported ‘improved’ sleep while using Valerian.1215 Valerian seems to cause sedation by increasing GABA levels in your brain. Valerian provides GABA as one of its natural compounds, prevents reuptake of GABA in neurons, and inhibits the enzyme that naturally degrades GABA in your brain.1216 Valerian helps ease menstrual cramps in women which naturally provides an anti-anxiety effect.1217 Valerian helps reduce hyperactivity in those dealing with ADHD.1218 Valerian reduces symptom severity in those with restless leg syndrome. And improves sleep quality.1219 Valerian extract has been used for years in Iran to treat epilepsy. One study in rats showed that Valerian (aqueous) extract provides this anticonvulsant effect by acting on adenosine receptors. Note however that petroleum ether-based extract of Valerian did NOT provide this benefit in epilepsy.1220 So, make sure that if you are buying a Valerian extract for epilepsy that you know exactly what type of extract the manufacturer is using. And that is it NOT petroleum-ether based. And Valerian also helps reduce the symptoms of OCD.1221 How does Valerian feel? The effects of supplementing with Valerian (Valeriana officinalis) can help tame anxiety and help you sleep. Valerian for sleep doesn’t act like prescription sleeping aids which make you feel you can’t stay awake. Instead, Valerian before bed helps your body and brain relax and allows you to drift off to sleep naturally. Some report experiencing vivid dreams when they take Valerian extract before bed.

Neurohackers report that Valerian extract is better than Valium® or Xanax® for combating stress without the side effects. If you are dealing with ADHD, you may find that adding Valerian to your stack will help calm you. And turn off your mind enough so you can get some rest. Neurohackers report that Valerian helps tame the symptoms of Restless Leg Syndrome. A few say it even helps calm the symptoms of Parkinson’s. Some say using Valerian helps eliminate migraines. Low dose Valerian may help alleviate social anxiety for some people. Valerian Clinical Research Valerian for sleep Valerian has been used to treat insomnia since ancient times. In an open label case with 11,168 patients, over 70% reported that Valerian was effective in helping them fall asleep, reduced sleep disturbances and decreased restlessness and tension.1222 If you live in a noisy environment and it’s affecting your sleep, you’ll like this one. A study conducted in Germany with a stack containing Valerian and hops reduced sleep disturbances caused by noise in a high-traffic area. This combo increased slow-wave and REM sleep.1223 Valerian helps ADHD Hyperactivity, impulsivity, and inattention are symptoms of ADHD. Symptoms that can often be attributed to low levels of GABA in the brain. A 3-week, double-blind, placebo-controlled pilot study was conducted to determine the efficacy of Valeriana officinalis tincture (MT) on ADHD. 30 children between the ages of 5 and 11 years, prediagnosed with ADHD, were recruited. Valerian tincture or placebo was given to the kids 3-times per day for 3 weeks. The study found a statistically significant improvement in the kids’ behavior with particular reference to sustained attention, anxiety and impulsivity and/or hyperactivity.1224 Valerian for OCD 31 outpatients diagnosed with Obsessive-Compulsive Disorder (OCD) were recruited to participate in a double-blind, randomized trial. Patients were randomly assigned a capsule of Valerian extract (765 mg) once per day or a placebo for 8 weeks. The study showed a significant difference between the Valerian and placebo group by the end of the treatment. The researchers concluded that Valerian extract has “anti-obsessive and compulsive effects” in patients

with OCD.1225 Valerian for stress reduction During World War 1, Valerian was used to prevent and treat shell shock in front-line troops. And was used during World War 11 to help calm the residents of London during air bombing raids.1226 More recently, a double-blind, placebo-controlled trial with 24 healthy volunteers received 3 separate doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing Lemon Balm and Valerian officinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. The results showed the 600 mg dose of this stack reduced anxiety. But the highest dose did not work as well as the lower dose stack. The research team concluded that the combination of Lemon Balm and Valerian extract possessed anxiolytic properties.1227 Valerian Recommended Dosage Recommended Valerian nootropic dosage for: •

•

Stress reduction – 200 – 600 mg Valerian extract (aqueous, standardized to contain 0.8% valerenic or valeric acid) o Valerian tea – 1.5 – 3 grams Valerian root steeped in boiling water Insomnia – 300 – 900 mg of Valerian extract (aqueous, standardized to contain 0.8% valerenic or valeric acid) 60 – 90 minutes before bed o Valerian tea – 1.5 – 3 grams Valerian root steeped in 150 mg boiling water taken 60 –90 minutes before bed o Lemon balm – 120 mg Valerian extract with 80 mg lemon balm extract 60 – 90 minutes before bed

Studies show it may take a week or two of continuous daily usage before you’ll experience the full effects of using Valerian. Higher dosages of Valerian extract should be taken in smaller amounts 2 – 3 times per day. For example, 600 mg Valerian daily would be 3 doses of 200 mg each. Valerian Side Effects Valerian is well-tolerated and safe for most people. But side effects can occur and include headaches, dry mouth, excitability, uneasiness, heart palpitations, stomach upset and even insomnia in some people. Although it’s rare, some report feelings of sluggishness the next morning. A few have reported vivid dreams when using Valerian. If you are prone to nightmares, Valerian may cause you to dream more and have more nightmares. Valerian root smells particularly nasty and is offensive to most people. If you can’t stand the smell, make sure you get this supplement in capsule form.

Valerian can interact with and should not used while on prescription antidepressants and benzodiazepines. Type of Valerian to buy The dried root or rhizome of Valerian officinalis is primarily used for its nootropic benefits. Valerian root is available in capsules, tablets, liquid extracts and as a tea. Valerian officinalis extract is available in capsules, tablets and powder form. The pharmacopeia name for Valerian root is Valerianae radix. Research shows that there can be considerable differences in Valerian content including essential oil, valerenic acid and derivatives, and valepotriates depending on where the Valerian is grown and when it’s harvested.1228 Adulteration of Valerian supplements is a problem world-wide with unscrupulous manufacturers substituting other species of plants. Including from the Valerian species but not officinalis. So make sure you choose a trustworthy manufacturer who clearly tests their product. And tests every single batch that comes in to their facility and has a 3rd party test the product after encapsulation and before the product is offered for sale. Nootropics Expert® Recommendation Valerian 200 – 600 mg per day I recommend using Valerian as a nootropic supplement. Your body does not make Valerian on its own. So you must take it as a supplement. Valerian is especially helpful for those suffering from anxiety, chronic stress, and insomnia. Valerian is reported to work well for those dealing with Obsessive Compulsive Disorder (OCD). Taming racing thoughts, and helpful in dealing with stressful situations. Valerian is also helpful for those suffering from the hyperactivity associated with ADHD. You can safely take up to 900 mg of Valerian daily if needed. One dose first thing in the morning. One dose early afternoon. And the last dose in the evening. Valerian as a sleep aid seems to be particularly effective when stacked with Lemon Balm. The two work in synergy to help promote sleep. But when combined, use lower doses of each.

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Vinpocetine Vinpocetine is known for increasing cerebral circulation, taming inflammation and oxidative stress, and boosting alertness, cognition, concentration, memory and mood Vinpocetine (periwinkle extract, ethyl apovincaminate, Cavinton, Bravinton, Ceractin, Intelectol) is a semi-synthetic derivative of vincamine, an alkaloid derived from the lesser periwinkle plant (Vinca Minor L.). A flowering plant native to central and southern Europe and Turkey, Vinca Minor is also grown as ground cover in the United States. Vinpocetine was first isolated from the periwinkle plant in 1975 by chemist Csaba Szántay. Hungarian pharmaceutical company Gedeon Richter began manufacturing Vinpocetine in 1978. Vinpocetine continues to be one of the company’s top selling drugs world-wide.1229 Vinpocetine is used as a prescription drug in Japan, Europe, Mexico and Russia for the treatment of cognitive and cerebrovascular disorders. In the USA and Canada, Vinpocetine is sold as an OTC dietary supplement. Other uses include using Vinpocetine for the prevention of motion sickness, menopause symptoms, chronic fatigue syndrome, seizure disorders, hearing and eye disorders, and even as a topical application to increase female sexual response.1230 Since it was first released in 1978, Vinpocetine has earned a well-deserved reputation with the nootropics community for optimizing cognitive health. Primarily by boosting cerebral blood flow. But to understand how and why Vinpocetine boosts cognition and protects your brain, we need to dive in to how blood flows in your brain. An optimized adult brain gets about 1/7th of your heart’s output of blood every minute. Your brain needs this blood flow for a constant supply of glucose, oxygen and other nutrients to keep it functioning properly. Unlike other organs and muscles in your body, your brain cannot stand an interruption in this steady flow of blood. Two carotid arteries in the sides of your neck send blood to the front and top of your brain. Arteries in your vertebrae (spine) join with your carotid arteries at the base of your brain to form the Circle of Willis.1231 The Circle of Willis is critical because it is the only area of your body where all four major blood vessels join. Allowing blood to be sent to areas where it is needed. Even if one of the major blood vessels becomes blocked. We’ll take a look at “How things go bad” later in this chapter. The good news is that Vinpocetine can have a profound effect on maintaining and repairing your brain’s blood vessels, cerebral blood flowing

through the Circle of Willis, and to individual brain cells. Vinpocetine not only helps increase cerebral blood flow, it also works as a powerful antioxidant and anti-inflammatory in your brain. And Vinpocetine inhibits the enzyme PDE1 which can increase cAMP and cGMP levels. These cyclic nucleotides in turn activate a series of kinases that phosphorylate the transcription factors cAMP response element binding protein (CREB) and serum response factor (SRF), leading to the expression of plasticity-related genes.1232 Boosting neuroplasticity enhances cognition and memory. How does Vinpocetine work in the Brain? Vinpocetine boosts brain health and function in several ways. But two in particular stand out. 1. Vinpocetine boosts cerebral circulation. Your brain only accounts for about 2% of your bodyweight, but it consumes about 20% of the oxygen and nutrients circulating in your blood.1233 This is why strong, healthy cerebral blood flow is so critical to your brain health and cognitive performance. Vinpocetine inhibits an enzyme called PDE1 (phosphodiesterase type 1) while reducing calcium levels in brain cells. When both of these are elevated, the smooth muscle in blood vessels contract, narrowing the diameter of blood vessels. And restricting blood flow to that area of the brain. You may be familiar with PDE5 inhibitors like Viagra® which work to dilate blood vessels and maintain healthy blood flow to your penis. Vinpocetine has a similar mechanism of action in your brain. In two separate clinical studies, chronic ischemic post-stroke patients were treated with either a single infusion, or daily infusion of Vinpocetine for 2 weeks. Vinpocetine increased cerebral glucose uptake and glucose metabolism in both the stroke region of the patient’s brains as well as the intact brain tissue. Patients in the 2-week long treatment also showed increased cerebral blood flow especially in the thalamus, basal ganglia and visual cortex regions of the brain.1234 2. Vinpocetine is an anti-inflammatory. Vinpocetine prevents the upregulation of NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) by TNFα (tumor necrosis factor alpha). This sounds a little complicated but has serious implications in the development of Parkinson’s and Alzheimer’s Disease. Here’s how it works… NFκB is a protein complex that controls transcription of DNA, cytokine production (signaling protein) and cell survival. TNFα is a signaling protein (cytokine) involved in inflammation produced by neurons. Vinpocetine inhibits this action. Vinpocetine also reduces the TNFα-induced expression of the mRNA of pro-inflammatory molecules such as interleukin-1β, monocyte chemoattractant protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1).

Researchers have found that Vinpocetine prevents this inflammatory response at the cellular nucleus level. And this mechanism of action is independent of Vinpocetine’s action on PDE1. This is a very big deal because TNFα contributes to the neuronal cell death found in Parkinson’s Disease. And there is growing evidence that the accumulation of amyloid-β protein leads to an upregulation of interleukins and TNFα that contributes to neurodegeneration leading to Alzheimer’s Disease. Scientists are now working on trying to determine if Vinpocetine can reduce inflammation in the brain. And help protect the brain from developing Parkinson’s or Alzheimer’s.1235 How things go bad Poor cerebral blood flow, inflammation and free radicals (oxidation) can damage your brain. And one of the ways this manifests is memory loss. Left unchecked, it can develop into serious neurodegenerative diseases like Alzheimer’s and Parkinson’s Disease. ↓ Cognitive function declines ↓ Inflammation kills brain cells from the inside ↓ Free radicals destroy neurons and synapses ↑ Anxiety, depression and moodiness increase ↓ Concentration and memory declines Poor cerebral circulation causes a domino effect in the brain affecting many critical processes. Memory, cognition, and decision-making all suffer as a result. Vinpocetine benefits Vinpocetine is one of the most researched nootropics on the planet. It was introduced to clinical practice in Hungary in 1978 for the treatment of cerebrovascular (brain blood flow) disorders and related symptoms. Since then Vinpocetine has become a “reference compound” in pharmacological research of cognitive deficits caused by hypoxia (oxygen deficiency), ischemia (inadequate blood supply) and research into cyclic nucleotides (cAMP and cGMP). Vinpocetine’s mechanism of action in the brain includes: • • • • • •

Increasing brain blood circulation and oxygen utilization Increased tolerance for hypoxia and ischemia Anticonvulsant activity Inhibiting the PDE1 enzyme Increasing the pliability of red blood cells Inhibiting the aggregation of platelets (blood clots)1236

Hundreds of studies in animals and humans have shown Vinpocetine can repair and reverse the effects of damage caused by strokes. Vinpocetine can prevent the inflammation and damage by free radicals that can lead to neurodegenerative diseases like Parkinson’s and Alzheimer’s. Vinpocetine can improve glucose and oxygen supply to critical brain cells through increased blood flow. Improving cognition, concentration, mental agility, anxiety, depression and memory. How does Vinpocetine feel? You should be able to feel the effects of Vinpocetine within an hour of taking it. Neurohackers report that Vinpocetine reduces brain fog and mental fatigue. Most experience improved focus, memory and even an improved sense of well-being. Vinpocetine’s effect on short-, working- and long-term memory can be profound. Remembering names, numbers and life events becomes easier. At work or in school, Vinpocetine can assist in learning and helping your brain commit it to memory. You should feel a significant difference in your ability to focus at work. Like any nootropic, Vinpocetine is not going to turn back the clock 30 or 40 years. But it will help to keep your brain functioning more smoothly. The Research Vinpocetine Improves Memory 12 healthy female volunteers were treated with 40 mg Vinpocetine 3-times per day, or a placebo, for 2 days in this randomized double-blind crossover study. On day 3 of the study, and one hour following morning dosage of Vinpocetine, the women completed a battery of psychological tests. The study found that those who used Vinpocetine had a significant improvement in memory when compared to placebo.1237 Vinpocetine Repairs Long-Term Potentiation If you have been having problems with long-term memory lately, this study is for you. Researchers produced a “medial septal lesion” on rats in the lab. The medial nuclei are an area of the brain composed of medium-size neurons. These neurons receive signals from different areas of your brain including your hippocampus. A lesion cuts off communication with an important memory-formation area of your brain. The effect of a lesion in this study was on hippocampus function and the long-term potentiation pathway. The scientists found that damage in this area of the brain negatively affects long-term potentiation. The rats were then given either physostigmine, piracetam, Vinpocetine or Hydergine one hour after the lesion. And once-a-day for 6 days after the operation. The study found that all of the drugs used in this study produced complete restoration of long-term

potentiation. And shows that Vinpocetine is one of the most effective and least expensive ways to restore long-term potentiation and long-term memory formation.1238 Vinpocetine Enhances Cognitive Performance A placebo-controlled, randomized double-blind trial was conducted at the University of Surrey with 203 dementia patients using Vinpocetine. Patients received either 10 mg of Vinpocetine 3-times per day, 20 mg of Vinpocetine 3-times per day or a placebo 3-times per day for 16 weeks. The patients were assessed on cognitive performance and measure of quality of life, including depression. The subjects using Vinpocetine experienced a significantly improved cognitive performance score compared to placebo. The study concluded that Vinpocetine was useful in the management of patients with symptoms of dementia. And there was no statistical difference in cognitive scores with 10 mg or 20 mg of Vinpocetine.1239 Dosage Notes Vinpocetine has a reputation among neurohackers and in clinical trials for safety at recommended doses. The recommended dosage for Vinpocetine is 10 mg taken 3-times per day with food. Vinpocetine seems to be more effective when taken with a meal or high quality fat like coconut or olive oil. You can safely dose up to 60 mg of Vinpocetine per day total. But clinical trials and user experience nearly always report that higher doses provide no added benefit. Side Effects Vinpocetine is well-tolerated and safe for use by most people. But if you’re particularly sensitive to supplements and drugs, try a starting dose of 5 mg of Vinpocetine and see how your body reacts. If you’re dealing with low blood pressure you should avoid using Vinpocetine. This nootropic affects blood flow not only in your brain, but through your entire system. If you take Vinpocetine and feel light-headed or dizzy it could be a sign your blood pressure is low. Vinpocetine affects clotting factors in your blood. And may decrease red blood cell platelet aggregation. So if you are using blood thinners or high doses of aspirin you should avoid Vinpocetine. Stop taking Vinpocetine at least 2 weeks before surgery because of its effect on blood thinning and flow. Available Forms Vinpocetine usually comes in 5, 10 or 20 mg tablets. Vinpocetine is available as an OTC supplement in the United States and Canada. Many countries around the world require a prescription to purchase Vinpocetine. Nootropics Expert® Recommendation

Vinpocetine 10 mg 3-times per day I recommend using Vinpocetine as a nootropic supplement. Your body does not make Vinpocetine on its own. So you must take it as a supplement. Vinpocetine easily crosses the blood-brain barrier and is available within an hour of taking it. Vinpocetine works more effectively if taken with food. Vinpocetine is especially helpful for those suffering from brain fog and memory loss. Vinpocetine helps increase cerebral blood flow bringing more oxygen and nutrients to brain cells. Vinpocetine is helpful for those dealing with stroke recovery. This nootropic helps restore blood flow to damaged areas of the brain affected by stroke. And helps prevent damage caused by the increase in free radicals typically released during stroke recovery. Vinpocetine is also helpful for those suffering from Alzheimer’s. It has been shown to boost blood flow to areas of the brain affected by amyloid-β protein aggregation. Vinpocetine helps tame inflammation associated with the disease. And studies are now underway to determine if Vinpocetine can prevent Alzheimer’s from taking hold in the first place. You can safely take up to 60 mg of Vinpocetine daily if needed. One dose first thing in the morning. One dose early afternoon. And the last dose in the evening. And for memory, Vinpocetine is great to stack with most of the racetams. Neurohackers report good success stacking Vinpocetine with Gotu Kola.

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Vitamin B1 (Thiamine) Vitamin B1 is known as an effective mosquito repellant, boosts motivation, improves focus, enhances memory, alleviates chronic pain, depression and anxiety Vitamin B1 (Thiamine) is the first B Vitamin to be discovered by researchers. “Thio-vitamine” refers to its sulfur-containing content. It’s called B1 because it was the first of the B complex vitamins to be identified. It was Kanehiro Takaki, surgeon general of the Japanese navy back in 1884 that figured something was amiss. Sailors were dying on his ships from a disease called Beriberi. And Takaki surmised it had something to do with sailors eating only white rice. It wasn’t until 1897 that Christiaan Eijkman, a military doctor in the Dutch East Indies figured out that the bran removed from white rice was causing problems. Something was missing in the diet. In 1911, Polish biochemist Casimir Funk isolated what he called a “vitamine” from rice bran. Dutch chemists went on to isolate and crystallize the active agent in 1926. US chemist Robert Williams determined the structure of Vitamin B1. And synthesized it in 1936.1240 In Japan, it was found that insufficient thiamine led to a central nervous system disorder called Beriberi. But supplementing with thiamine alone didn’t help because of its poor bioavailability. A lot of thiamine was needed to cure Beriberi symptoms. So Japanese scientists created a derivative of Vitamin B1 called Sulbutiamine in an attempt to quell the health crisis within the Japanese population. Sulbutiamine is far more bioavailable than standard thiamine. It is fat-soluble (thiamine is watersoluble) which helps it more easily cross the blood-brain barrier. Advanced neurohackers add Sulbutiamine to their stack instead of standard Vitamin B1 (thiamine) because it’s better absorbed and used by your brain than B1. Thiamine is a coenzyme used by your body to metabolize food for energy. And to maintain proper heart, nerve, and brain function. Thiamine also helps digest and extract energy from food. It helps turn nutrients into adenosine triphosphate (ATP). ATP is the cellular fuel used by your cells and synthesized in your mitochondria. And thiamine helps convert carbohydrates into glucose. The energy your body uses for your brain and nervous system. One more thing about this miracle B-vitamin. Thiamine contributes to the development of myelin sheaths which wrap around neurons to protect them from damage. Your body does not produce thiamine on its own. So you must get it from food including beef, brewer’s

yeast, legumes (beans, lentils), milk, nuts, oats, oranges, pork, rice, seeds, wheat, whole-grain cereals, and yeast. Thiamine vs. Sulbutiamine: What’s the Difference? Sulbutiamine is a synthetic version of Vitamin B1 (Thiamine). It is two B1 molecules chemically bonded together. Thiamine is water-soluble and does not easily cross the blood-brain barrier. Sulbutiamine is a fatsoluble compound that easily crosses the blood-brain barrier. Sulbutiamine functions in the body just like thiamine. But because it’s more bioavailable it’s more effective than thiamine. How does Vitamin B1 (Thiamine) work in the Brain? Vitamin B1 (Thiamine) boosts brain health and function in several ways. But two in particular stand out. 1. Thiamine increases levels of thiamine pyrophosphate (TPP). TPP is directly involved in the citric acid (KREB) cycle in the brain. This cycle breaks fatty acids, amino acids and monosaccharides into smaller molecules that produce adenosine triphosphate (ATP) energy within your mitochondria. And provide the building blocks of the molecules needed to produce brain cells. A deficiency of TPP can eventually show up as Wernicke encephalopathy and Korsakoff syndrome. In our society this syndrome is typically caused by chronic alcoholism. But it can also occur after obesity (bariatric) surgery, Crohn’s disease, anorexia, diabetes, and if you’re on kidney dialysis. Symptoms of Wernicke-Korsakoff syndrome include confusion, inability to form memories, loss of memories and muscle coordination, confabulation (making up stories) and vision changes. And can ultimately (and very rapidly) lead to coma and death.1241 Less severe cases of thiamine deficiency include fatigue, weight loss, irritability and confusion. 2. Thiamine also contributes to the production of the enzyme PDH which is essential for making the neurotransmitter acetylcholine. And for the synthesis of myelin, which forms a sheath around the axons of neurons. Ensuring these neurons can conduct signals.1242 The citric acid (KREB) cycle and enzyme α–KGDH play a role in maintaining optimal levels of the neurotransmitters glutamate, and gamma–aminobutyric acid (GABA). When thiamine levels decrease, the activity of these enzymes are reduced.1243 How things go bad We depend on our diet for thiamine. Very little thiamine is stored in your body. And depletion can occur within 14 days.

Thiamine deficiency can be caused by alcoholism, Alzheimer’s Disease, anemia, athletes who reduce food intake, cancer, clogged arteries, Crohn’s disease, diabetes, diarrhea, gastric bypass surgery and kidney disease. And even a poor diet. Several foods are also considered “anti-thiamine factors” (ATF) and contribute to the risk of thiamine deficiency in otherwise healthy people. Certain plants contain ATF, which react with thiamine to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nuts, have been associated with thiamine depletion in humans.1244 ATF include mycotoxins (molds) that break thiamine down in the blood. If you eat certain raw, freshwater fish, raw shellfish, and ferns you are at a greater risk of thiamine deficiency.1245 Thiamine is also inactivated by cooking food. Thiamine is a cofactor of several enzymes including transketolase, pyruvate dehydrogenase, and alphaketoglutarate dehydrogenase. Thiamine deficiency decreases cerebral glucose utilization which results in mitochondrial damage. Scientists have seen through the electron microscope; disintegrating mitochondria, chromatin clumping, and swelling of degenerating neurons. Yikes! ↓ Low thiamine levels can slow creation of ATP ↓ Energy levels drop ↓ Low thiamine levels can cause problems with memory, learning, recall and perception ↓ Acetylcholine levels decline ↓ Blood pressure drops, reflexes decline, and calf muscles get tender ↓ Heart muscles enlarge ↓ Severe thiamine deficiency can result in psychosis Thiamine supplementation can help nearly every active adult, as well as a student looking to do better in school. By boosting acetylcholine, glutamate and GABA in the brain. Providing increased brain energy by fueling cell mitochondria with ATP. And building myelin sheaths that protect our neurons. Vitamin B1 (Thiamine) benefits Thiamine occurs in your body as free thiamine and as various phosphorylated forms: thiamine monophosphate (TMP), thiamine triphosphate (TTP), and thiamine pyrophosphate (TPP), which is also known as thiamine diphosphate. The synthesis of TPP from free thiamine requires magnesium, adenosine triphosphate (ATP), and the enzyme thiamine pyrophosphokinase. TPP is required for the metabolism of carbohydrates and branched-chain amino acids.

Thiamine is directly involved in the citric acid (KREB) cycle that is needed for adenosine triphosphate (ATP) energy production within your mitochondria. Thiamine also plays a role in maintaining optimal levels of the neurotransmitters glutamate, and gamma–aminobutyric acid (GABA). And contributes to the production of the enzyme pyruvate dehydrogenase (PDH) which is essential in making the neurotransmitter acetylcholine. Thiamine will boost cognition, memory and decision-making. And provides very effective anxiolytic (anti-depressant) qualities. How does Vitamin B1 (Thiamine) feel? Thiamine is water-soluble and has been shown to improve glutamate, and γ-aminobutyric acid (GABA) neurological transmissions.1246 If you are perfectly healthy and don’t have a thiamine deficiency, you’ll likely not feel anything after supplementing with thiamine. But I’ve come across study after study, and reports on forums, where lab tests showed thiamine and thiamine pyrophosphate within range. And yet people were dealing with “mild thiamine deficiency”. The problem is “mild thiamine deficiency” can turn your world upside down. If you are hypothyroid or dealing with Hashimoto’s there is a very good chance you would benefit from thiamine supplementation. Same with diabetes, fibromyalgia and inflammatory bowel disease. Neurohackers report that supplementing with thiamine is an effective mosquito repellent. I personally have found that when those around me are getting eaten by mosquitoes I avoid the bites because I’m supplementing with Sulbutiamine twice per day. Many report thiamine supplementation boosts attention, energy, and motivation. A reduction in brain fog and increased mental clarity with less anxiety. Those dealing with fibromyalgia and nerve pain report a significant decrease in pain levels. The Research Most of the research conducted on Vitamin B1 (Thiamine) has been with people dealing with fatigue or pain associated with fibromyalgia, thyroid disease and other debilitating conditions. And most have very few participants. But the results in every trial I’ve reviewed are profound. Vitamin B1 (Thiamine) Improves Symptoms of Fibromyalgia If you’ve ever had to deal with fibromyalgia, you are familiar with the hell of living with chronic pain, fatigue, insomnia and more. Some studies suggest that many of the symptoms of fibromyalgia could be related to mild thiamine deficiency due to a dysfunction of the active transport of thiamine from blood to the mitochondria. One very small study conducted in Italy recruited 3 female patients with fibromyalgia. Levels of

thiamine and thiamine pyrophosphate in the blood were measured. The patients then received from 600 mg to 1800 mg of thiamine per day. And the results were astounding: • • •

Patient 1: 71.3% reduction in fatigue; 80% reduction in pain Patient 2: 37% reduction in fatigue; 50% reduction in pain Patient 3: 60.7% reduction in fatigue; 60% reduction in pain

One patient reported improvement at 600 mg of thiamine. Doses for the other 2 patients were increased by 300 mg every 3 days. And experienced improvement in their symptoms at a dose of 1500 mg. None of the patients experienced side effects.1247 Vitamin B1 (Thiamine) for Chronic Fatigue If you deal with chronic fatigue, Thiamine may be a better option than another cup of coffee. Or a stimulant. Researchers in Italy noted that previous studies on fatigue and related disorders like inflammatory bowel disease improved after therapy with high-dose thiamine. The team chose 3 stroke patients who also experienced fatigue. Severity of fatigue was assessed using the Fatigue Severity Scale. Note that lab tests showed free thiamine and thiamine pyrophosphate levels were within the healthy reference range in all the patients. High-dose thiamine therapy was started. And resulted in a significant decrease in fatigue. The researchers concluded that post-stroke fatigue and related disorders could be a manifestation of mild thiamine deficiency. Likely due to dysfunction of intracellular transport of thiamine, or other enzyme abnormalities.1248 Vitamin B1 (Thiamine) and Hashimoto’s Thyroiditis Researchers in Italy hypothesized that the chronic fatigue accompanying inflammatory and autoimmune diseases is a clinical manifestation of mild thiamine deficiency. Hashimoto’s thyroiditis is both an autoimmune disease and cause of hypothyroidism. In this study, 3 Hashimoto’s patients complaining of chronic fatigue were recruited. All 3 patients received 600 mg of thiamine per day, or 100 mg of thiamine intravenously (IV) once every 4 days. Thiamine treatment led to partial or complete remission of fatigue within a few hours or days.1249 Dosage Notes The recommended dosage of Vitamin B1 (Thiamine) according to the American FDA is 1.2 mg per day. Pregnant and breastfeeding women is a whopping 1.4 mg per day. Many neurohackers would laugh at these recommendations. “Mild thiamine deficiency” affects a significant segment of the population in any country.

Most clinical studies use thiamine doses from 300 up to 1800 mg per day. The bottom-line is thiamine dosing is completely up to you. No side effects are reported even at higher doses. The Mayo Clinic recommends: • • • • • •

Menstrual cramps – 100 mg per day Epilepsy – 50 mg per day Alcoholic liver disease and withdrawal – 100 mg injections of thiamine hydrochloride Coma or hypothermia – 100 mg injections Thiamine deficiency due to nutrition – 100 mg injections Wernicke-Korsakoff Syndrome – 5 – 200 mg injections1250

Some natural health clinics offer (expensive) thiamine therapy intravenously (IV) and doses are usually 25 – 50 mg per session. Side Effects Vitamin B1 (Thiamine) is non-toxic. So is considered well-tolerated and safe. Side effects are rare but very high doses can include stomach upset. If you are taking Digoxin, diuretics or Dilantin you should consult your doctor before supplementing with thiamine. Available Forms Thiamine hydrochloride (HCl): Most Vitamin B1 (Thiamine) supplements available from online retailers and vitamin shops come as Thiamine hydrochloride (HCl). And come in 50 – 500 mg tablets. Benfotiamine (S-benzoylthiamine O-monophosphate) is a synthetic S-acyl derivative of thiamine. This fat-soluble form of thiamine is much more bioavailable than HCI. Benfotiamine typically comes in 150 – 250 mg capsules. Dosage is up to 900 mg per day. Tetrahydrofurfuryl disulfide (TTFD) (Fursultiamine): TTFD is a disulfide derivative of thiamine developed in Japan for treating Beriberi. It’s a synthetic form of thiamine that mimics the naturally occurring thiamine produced in garlic.1251 TTFD is a form of thiamine that is water-soluble, and much more difficult to find in vitamin shops. Brand names include Lipothiamine, Allithiamane, Adventan, Alinamin-F, Benlipoid, Bevitol Lipophil, Judolor. TTFD comes in 50 mg capsules. And the primary side effect is you smell like garlic after taking it. Sulbutiamine: Sulbutiamine is my preferred form of Vitamin B1 (Thiamine) for cognitive enhancement. Sulbutiamine is sold in tablet, capsule, and powder form. Tablets and capsules are usually 750 mg each. Sulbutiamine is a synthetic version of thiamine (two thiamine molecules bound together). It’s sold as a

prescription medication in some countries under the brand names Arcalion, Enerion, Bisibuthiamine, and Youvitan. Nootropics Expert® Recommendation Vitamin B1 (thiamine) 50 - 100 mg per day I recommend using Vitamin B1 (Thiamine) as a nootropic supplement. Your body does not make thiamine on its own. So to get its benefits you must get it from food or take it as a supplement. Vitamin B1 is especially helpful for those suffering from low energy levels, anxiety, depression, and chronic pain. Experience shows thiamine helps stop and reverse the symptoms associated with fatigue. Likely because this nootropic helps boost the activity of acetylcholine, GABA and glutamate in the brain. Thiamine is also a very effective mosquito repellant. I live in SE Florida where we’re currently under a Zika scare. But I do not experience problems with mosquitoes. Likely because of adequate thiamine levels in my body. Personally, I’ve found Sulbutiamine to be much better for cognition than standard thiamine. And more effective (and safer) than any prescription anti-depressant I’ve ever tried. Sulbutiamine is also particularly helpful to students and executives who want to boost cognition, learning and memory. Vitamin B1 can produce a noticeable increase in mental clarity. And give you a significant energy boost physically and mentally. You’ll feel more awake and alert. Without the side effects you’d get from stimulants like caffeine. Vitamin B1 is a must have addition for any nootropic stack. If you are using any of the racetams like Piracetam and Aniracetam you may want to consider adding Sulbutiamine as well.

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Vitamin B3 (Niacin) Vitamin B3 is known for increased alertness, clarity, focus, memory, enhanced mood and energy, is a potent antioxidant and free radical scavenger, lowers LDL-cholesterol, increases HDL-cholesterol and lowers triglycerides Vitamin B3 (Niacin, nicotinic acid, 3-pyridine-carboxylic acid) is one of eight B-Vitamins. Niacin is a precursor to the coenzymes nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP). NAD is needed to catabolize fats, carbohydrates, proteins, and alcohol. And NAD is involved in cell signaling and DNA repair. Niacin is found in, and critical for the health of every cell in your body. NADH is the reduced form of NAD (Nicotinamide Adenine Dinucleotide), making it the “active” form which can donate electrons. NADH is the primary carrier of electrons from glucose and lactate for adenosine triphosphate (ATP) synthesis. ATP is the fuel source made within mitochondria. The power supply in each of your brain cells. So you need niacin to produce NADH to transfer the energy from the food you eat into a type of energy your body can use. Not enough NADH leads to ATP depletion, which can eventually lead to cell death.1252 Studies have shown that supplementing with niacin improves cognitive function, enhances cellular energy, boosts cerebral circulation, increases endurance, switches ‘off’ aging genes, and extends life span. Niacin naturally occurs in foods like eggs, fish, meat, milk, peanuts, mushrooms, green vegetables, and yeast. Your body also naturally synthesizes niacin from the amino acid tryptophan you get from food. This synthesis requires Vitamin B6, riboflavin and an enzyme containing iron. But only about 2% of dietary tryptophan is converted to niacin. Not nearly enough that your body requires which is why supplementation is needed. Niacin supplementation has been used to treat addiction, ADHD, arthritis, Alzheimer’s Disease, depression, memory loss and schizophrenia. And for detoxing nearly every foreign substance that can find its way into your fat cells. The Russian-designed nootropic Picamilon is a combination of niacin and GABA. And is used to improve memory, concentration, focus, relieve anxiety and lower blood pressure. As a nootropic, niacin helps boost cognition, memory and neuroplasticity. How does Niacin work in the brain?

Niacin boosts brain health in several ways. But two in particular stand out. 1. Niacin increases cellular energy. Niacin is the precursor to NAD. NAD acts as an electron carrier, meaning it can accept and donate electrons to various enzymes involved in energy metabolism. NAD is transformed into NADH. NADH then donates its electron to the electron transport chain where a number of ATP molecules are formed. Using niacin as a supplement increases the available NAD molecules that can take part in energy metabolism. And increasing the amount of energy in each cell.1253 By providing the means for ATP synthesis, niacin is involved in cognition, focus, concentration, memory, and processing speed. And niacin plays an important role in mediating brain aging and tissue damage. Even decreasing the damage done by strokes. Researchers at Massachusetts General Hospital in Boston studied the neuroprotective effects of CoQ10 and niacin in mouse models of Parkinson’s Disease (PD). Impaired energy metabolism has been associated with some symptoms of PD. Researchers administered MPTP which is poison to neurons. It disrupts the energy metabolism of neurons that release dopamine. The affected dopamine cells are also unable to release as much glutamate which results in decreased dopamine in people with PD. The combination of CoQ10 and niacin protected against both mild and moderate dopamine depletion. The researchers concluded that CoQ10 and niacin improve mitochondrial energy production.1254 2. Niacin increases Brain Derived Neurotrophic Factor (BDNF). BDNF has been termed “Miracle-Gro for the brain”. Higher levels of BDNF have been associated with increased intelligence, mood, productivity and memory. Researchers at Henry Ford Hospital in Detroit tested the hypothesis that niacin could increase synaptic plasticity and axon growth in stroke patients. Male Wistar rats were purposely given a stroke and then treated with extended release niacin (Niaspan) for 14 days. Niacin increased synaptic plasticity and axon growth as a result of restored BDNF.1255 Another study published in the Journal of Clinical Endocrinology and Metabolism showed that niacin stimulated growth hormone.1256 How things go bad Niacin deficiency is considered rare by government health agencies, particularly in the West. But even mild niacin deficiency can have a negative impact on your health and cognition. Mild niacin deficiency can be caused by digestive problems that decreases the amount of Vitamin B3 (niacin) or tryptophan that your body absorbs.

If you are gluten intolerant, you’re at a higher risk of being niacin deficient. If you have Irritable Bowel Syndrome (IBS) or Crohn’s Disease you have an increased chance of niacin deficiency. Excessive alcohol consumption, birth control pills, anorexia, and those on a vegan diet can be deficient in niacin. ↓ Energy levels decline ↑ Fatigue increases ↓ Anxiety, hyperactivity, depression, headaches and hallucinations ↓ Metabolism declines ↑ Insomnia increases ↑ Irritability increases Some experts believe a lack of niacin and other B-Vitamins is at least partially responsible for the large increase in mental health disorders and violent crimes in recent decades.1257 All of these niacin deficiency-related changes are contributing factors to the neurodegenerative diseases of aging, age-related cognitive decline, including Alzheimer’s and schizophrenia. But even if things haven’t degenerated to such a debilitating level, niacin can help. Niacin benefits Research has shown that people with low niacin levels are far more vulnerable to addiction, depression, heart disease, schizophrenia, and other chronic conditions. Low niacin levels can happen at any age. Even at birth. Niacin can improve cholesterol levels. Supplementing with niacin has been shown to help those who are at increased risk for heart attacks, stroke, and other forms of heart disease. Niacin can help reduce hardening of the arteries (atherosclerosis) and assist in avoiding heart disease. And niacin helps reduce inflammation. Niacin plays a role in diabetes treatment because it helps balance blood sugar levels. Niacin helps to reduce skin inflammation, flare ups, irritation, redness and for treating severe cases of acne. Niacin can help protect against Alzheimer’s and dementia.1258 Niacin supplementation is also associated with decreased risk for age-related cognitive decline, memory loss, migraines, depression, motion sickness, insomnia and even alcohol dependence. Niacin is also used for treating and to help prevent schizophrenia. Studies show that niacin supplementation lowers the risk or severity of ADHD.

Niacin is an effective treatment for erectile dysfunction (ED) because it acts as a vasodilator that helps improve blood flow to the penis. How does Niacin feel? Niacin supplementation can help relieve depression and anxiety. Circulation should improve and you’ll feel like you have more energy. People taking statins to control cholesterol report severe side effects. But when adding niacin to their supplement stack, most experience a reduction in blood pressure. And some have stopped taking statins as a result. Those dealing with Obsessive Compulsive Disorder (OCD) report combining niacin with St. John’s wort reduced OCD symptoms. And was better than using the SSRI Prozac®, or the benzodiazepine Ativan® (lorazepam). Taken before bedtime some neurohackers report a reduction in insomnia. Lower back pain and hip pain may be reduced with niacin supplementation. Niacin can help reduce severe acne and other skin inflammation problems. The Research Niacin helps Reduce Bad Cholesterol Therapeutic doses of niacin have been shown to reduce serum cholesterol. Niacin significantly increases HDL-cholesterol (good cholesterol), decreases LPL-cholesterol (bad cholesterol) and triglycerides. Changes in blood lipid profile considered to be protective of your heart. Low levels of HDL-cholesterol are one of the major risk factors for coronary heart disease. And an increase in HDL levels is associated with a reduction of that risk. The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of niacin in 8,241 men aged 30 to 64 years old. All men had experienced some type of heart problem. Compared to placebo, patients who took 3 grams of niacin daily experienced an average 10% reduction in total blood cholesterol, a 26% decrease in triglycerides, a 27% decrease in recurrent heart attacks, and a 26% decrease in stroke.1259 Niacin for Detox If you are dealing with chronic health issues, chances are good you could benefit from a detoxification program. Even if you’re feeling perfectly ‘healthy’ you could likely use a good detox. Simply living in our modern society exposes us to thousands of chemicals that have the potential to get into our bodies from the food we eat, air we breathe, water we drink and things we touch. One study done in Portland, Oregon investigated the effects of a 7-day detox program on well-being in

25 disease-free, healthy participants. The 7-day detox produced a statistically significant (47%) reduction in the Metabolic Screening Questionnaire scores. And a 23% increase in liver detox capacity.1260 Even healthy people feel better after detox. In 1977, L. Ron Hubbard developed his “Sweat Program” to facilitate detox. The program includes niacin, sauna, and a supplement regimen to restore critical vitamins and minerals to the newly detoxed body. This niacin detox program has been used to treat Gulf War Syndrome, the fire fighters and first responders to the 9/11 attacks in New York1261, and is used by hundreds of naturopaths. Niacin affects adipocytes which causes an increase in free fatty acid (FFA) release from adipose tissue (body fat). Release of free fatty acids releases fat-stored toxins for excretion from the body. Niacin also causes prostaglandin D2 release which dilates small blood vessels in the skin. The same reaction responsible for the “niacin flush”. This dilation increases the movement of xenobiotics (foreign chemicals) for excretion through sweating (which is where the sauna comes into the detox program). Niacin is also a precursor to NADH which regenerates the master antioxidant glutathione. Niacin reduces inflammation by decreasing reactive oxygen species and inflammatory cytokines. Niacin helps treat Depression Niacin is especially helpful if you are taking antidepressants. Drugs to treat depression have an antiinflammatory effect, including inhibition of the rate-limiting enzyme of the kynurenine pathway. This metabolic pathway is involved in the production of NAD and NADH. The inhibition of this pathway increases serotonin as more tryptophan becomes available for serotonin synthesis. More serotonin helps decrease depression. But this also leaves less tryptophan available for niacin synthesis. Which causes depression and basically cancels out the benefits of using antidepressants.1262 So if you’re on SSRI’s you may want to add niacin to your stack. Niacin for the Treatment of Erectile Dysfunction Dyslipidemia is the name of the condition involving high LDL-cholesterol (bad), high triglycerides (bad), and low HDL-cholesterol (bad). Dyslipidemia is closely related to erectile dysfunction (ED). Researchers in Hong Kong ran a placebo-controlled trial with 160 male patients with ED and dyslipidemia. Half the men with ED received 1500 mg of niacin, and the other half received a placebo daily for 12 weeks. The main outcome of the study was a significant improvement in erectile function. And the researchers concluded that “niacin alone can improve erectile function in men suffering from moderate to severe ED”.1263 Dosage Notes

Niacin is naturally produced in your body from tryptophan. And you get niacin from eating certain foods including beef, chicken, tuna, sunflower seeds, salmon, green peas, turkey, and mushrooms. So niacin is considered non-toxic and safe. Note that higher doses of niacin are usually divided into evenly split doses 2 – 4 times per day. So 2 gram of niacin daily would be 500 mg 4-times per day. • • • • • • • •

• •

Prevention of heart disease: niacin 4 grams per day Lowering bad cholesterol and boosting good cholesterol: niacin 4 grams per day To slow the progression of newly diagnosed type 1 diabetes: Niacinamide 25 mg/kg of body weight daily Preventing or treating Vitamin B3 (niacin) deficiency: 50 – 100 mg per day To treat pellagra (severe niacin deficiency): 300 – 500 mg daily For treating osteoarthritis: Niacinamide 3 grams per day For reduced risk of cataracts: 44 mg of niacin per day Preventing Alzheimer’s Disease: 100 mg per day. Note that there is no reliable evidence that niacin can prevent Alzheimer’s although there is plenty of evidence that Alzheimer’s patients consistently show low niacin levels. Treating erectile dysfunction (ED): 500 mg 3-times per day Treating schizophrenia: 3 grams of niacin and 3 grams of ascorbic acid (Vitamin C) daily1264

Side Effects Standard niacin (nicotinic acid) is naturally produced in your body. And considered non-toxic. Niacin can lower blood pressure so if you are on blood pressure lowering medication be cautious about supplementing with niacin. Niacin may decrease the effectiveness of diabetes medication because long-term use of niacin can increase blood sugar. So you may need to increase your diabetes meds. Statins are notorious for causing muscle wasting. And when combined with niacin it may increase this muscle wasting problem. You may want to cut back on your statins as you increase your niacin dose. Many stop taking statins altogether when using niacin. Niacin (nicotinic acid) and sustained-release niacin causes “flushing” in many people. Here we address how to reduce or eliminate the side effect of niacin flushing. Preventing Niacin Flushing Regular immediate-release niacin (nicotinic acid) causes “flushing” in many people. And they avoid supplementing with niacin as a result. Standard niacin flushing results from activation of the niacin receptor G protein-coupled receptor 109A (GPR109A) in skin Langerhans cells. This leads to the production of prostaglandins, including prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2), which act on receptors in the capillaries (small blood vessels in your skin).1265

This flushing sensation comes from blood vessel dilation and manifests itself as redness, warmth of the skin and tingling or itching. It happens rapidly and lasts for about 1 hour. This flushing sensation is NOT an allergic reaction. And only feels uncomfortable. Here are some strategies to avoid niacin flushing. First, “slow-release” niacin may prevent flushing. But is NOT the answer because it will not provide the LDL-cholesterol (bad) lowering benefits. And can be toxic to your liver when used long-term.1266 Inositol hexanicotinate is commonly referred to as no-flush niacin or flush-free niacin and is preferred by many neurohackers. Even though I’ve seen a couple of clinical studies claiming this version of niacin has no effect on lipid profiles when it comes to cholesterol1267, user reviews consistently report the opposite. They do not experience flushing with Inositol hexanicotinate even at high doses, and their cholesterol and triglyceride levels all benefited and came within a healthy range. A newer version of “extended-release” niacin called Niaspan® does not produce the flushing effect. And has been shown to have the same effects on good cholesterol and triglycerides as instant-release niacin.1268 Niaspan® is prescription-only and is now available as a prescription generic at lower cost. One effective way to reduce flushing with instant-release niacin and extended-release niacin is to take a 325 mg aspirin tablet 30 minutes prior to taking your niacin.1269 You can also try splitting your dose of niacin into smaller doses taken throughout the day. Flushing will be reduced if not completely eliminated. And long-term niacin users note that flushing goes away after about a week of long-term niacin use. Available Forms Vitamin B3 (Niacin) is not stored in your body and must be ingested daily from food or as a supplement. Niacin as a supplement comes in several forms: •

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Niacin (nicotinic acid, (pyridine-3-carboxylic acid) or ‘free-form’ nicotinic acid even at large doses of 3 or 4 grams are nearly completely absorbed by adults. This version causes ‘flushing’ above 50 mg which can be avoided. Refer to the “Side Effect” section of this article on niacin. Doses above 1500 mg per day can be toxic to your liver. Niacinamide (nicotinic acid amide) has a similar profile to that of free form niacin. But unlike free-form niacin does not produce a flushing effect. Doses above 3 grams per day can be toxic to your liver. Slow-release niacin is nicotinic acid using an ion exchange or wax matrix developed to slowly release niacin to avoid the flushing effect. Liver toxicity has been shown in doses above 500 mg of extended-release niacin. Inositol hexanicotinate (IH) is an “extended-release niacin” sold as “Flush Free Niacin” and has 6 molecules of niacin covalently bonded to one molecule of inositol. The IH version of niacin

does not produce a flushing effect. Studies show that an average of 70% of the dose you take gets absorbed by your body. Studies show that the benefits to lowering bad cholesterol with the IH form of niacin are not nearly as effective as free-from niacin.1270 But user reviews are the opposite of these clinical findings. No toxicity is associated with high doses of IH. Slo-Niacin®, is sold over the counter. Niaspan® is an extended-release niacin formula sold as a prescription drug. Note: Both slow-release niacin and extended-release niacin (inositol hexanicotinate) are marketed and labeled as “Flush-Free Niacin”. But they are not the same and you should avoid slow-release niacin. Slow-release niacin causes liver toxicity at relatively low doses and does not provide the lipid balancing effects like free-form niacin and extended-release niacin. Nootropics Expert® Recommendation Vitamin B3 (Niacin) 1000 mg 3-times per pay I recommend using Niacin as a nootropic supplement. Your body does make some Niacin on its own. And you can get it by eating meat, poultry, and fish. But studies have shown we don’t get an adequate supply of Niacin from food sources. Niacin is particularly helpful for vegetarians because very little Niacin is available from vegetables. Niacin is especially helpful for those suffering Chronic Fatigue Syndrome and ADHD. I suggest starting with a dose of 500 mg daily. And Niacin is a great compliment to a stack including any nootropic. Do your best to use free-form niacin if you can tolerate the flush. Or even better, use an extended-release version of niacin that has no flush and no associated toxicity. You need to provide the mitochondria in your brain with the nutrients required to make ATP which is your main source of cellular energy. Or neurons start to break down from the inside. NADH carries the electrons needed for the synthesis of ATP. Signs that your lacking adequate NADH is brain fog, slow thinking, fatigue, and low endurance. Some clinics in the USA and other countries are using Niacin therapy as a treatment for addiction, anxiety, depression, chronic stress and even schizophrenia. I recommend starting with a low dose of Niacin until you build a tolerance to avoid the niacin “flush”. Increase your dose every few days until you get to the dose you find gives you the most cognitive benefit.

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Vitamin B5 (Pantothenic Acid) Vitamin B5 is known to enhance alertness, cognition, energy, hearing, vision, elevate mood, lower anxiety and normalize healthy cholesterol levels Vitamin B5 (Pantothenic Acid) is one of 8 water-soluble B-vitamins that are absolutely vital to the highly optimized brain. And is essential to all forms of life. Vitamin B5 is found in every cell in your body including your brain. The name Pantothenic is derived from the Greek word pantothen, meaning “from everywhere”. Reflecting the idea that small amounts of pantothenic acid can be found in nearly every food. Foods rich in pantothenic acid include animal organs (liver and kidney), fish, shellfish, milk products, eggs, avocados, legumes, mushrooms, and sweet potatoes. Avocados contain the highest amount of pantothenic acid among commonly consumed foods, with one avocado containing about 2 mg. Pantothenic Acid is a precursor in the biosynthesis of Coenzyme-A (CoA). CoA is an essential enzyme in a variety of chemical reactions that sustain life. CoA as Acetyl-CoA is required for generating energy from fat, carbohydrates, and proteins. This energy in the form of glucose is the fuel source for each cell. Acetyl-CoA is also involved in the citric acid cycle (KREBs), in the synthesis of essential fats, cholesterol, steroid hormones, vitamins A and D, and the neurotransmitters acetylcholine (ACh) and serotonin. Coenzyme A derivatives are also required for the synthesis of melatonin which controls your circadian rhythm and sleep/awake cycle. And for the metabolism of drugs and toxins in your liver. Vitamin B5 is essential for the synthesis of acetylcholine (ACh). Adequate levels of ACh can boost focus, memory, learning, and reduce brain fog. Vitamin B5 is critical for converting nutrients from food into energy, balancing blood sugar, reducing LDL-(bad) cholesterol, lowering blood pressure, preventing nerve damage and pain, and preventing heart failure. Vitamin B5 plays a part in the synthesis and metabolism of proteins, carbohydrates, and fats. Turning them into energy that your brain uses to fire neurotransmitters in your brain. Vitamin B5 is required for the manufacture of red blood cells, and the stress and sex hormones produced in your adrenal glands. As a nootropic, Vitamin B5 is crucial for converting the choline in your nootropic stack into acetylcholine (ACh). Without adequate levels of B5 you will not experience the benefits of using precursors to ACh like Alpha GPC and CDP-Choline.

How does Vitamin B5 (Pantothenic Acid) work in the Brain? Vitamin B5 (Pantothenic Acid) boosts brain health and function in several ways. But two in particular stand out. 1. Vitamin B5 increases energy. Pantothenic acid is an essential coenzyme involved in mitochondrial aerobic respiration. Vitamin B5’s role in the citric acid cycle (KREBs) and electron transport chain helps convert nutrients from food into energy which is used to make adenosine triphosphate (ATP). ATP is the fuel source within each of your cells. Pantothenic acid takes part in the synthesis of Acetyl-CoA which is at the heart of the KREBs cycle. Acetyl-CoA in your brain is also involved in the synthesis of cholesterol, amino acids, phospholipids, and fatty acids. CoA is also involved in the synthesis of the neurotransmitters acetylcholine and serotonin, and steroid hormones. User reviews of those supplementing with pantothenic acid claim to having more energy. This boost in energy comes from this long series of events stemming from pantothenic acid.1271 2. Vitamin B5 helps reduces stress. Pantothenic acid is often referred to as the “anti-stress vitamin”. Your adrenal glands use CoA (made partly from pantothenic acid) along with cholesterol and Vitamin C to manufacture cortisol and epinephrine. When cortisol levels are low, your ability to cope and respond to stress is compromised. And if your cortisol levels are abnormally high (a common problem), your body’s reserve of pantethine (the active form of pantothenic acid) needs to be replenished in order to sustain good adrenal function.1272 Vitamin B5 has a reputation for reducing stress, anxiety and depression. How things go bad Chronic stress, anxiety and lower acetylcholine levels can damage your brain. This damage can manifest in several ways including memory loss, brain fog, anxiety, depression, and even neurodegenerative diseases like Alzheimer’s and Parkinson’s. ↓ Acetylcholine synthesis declines ↓ Concentration, memory, learning, and recall decline ↑ LDL-cholesterol (bad) and triglycerides increase ↓ HDL-cholesterol (good) levels decline ↓ Wound healing takes longer ↓ Energy levels decline ↑ Numbness, tingling, burning sensations, shooting pain in the feet increase

Vitamin B5 supplementation can help increase acetylcholine, epinephrine and serotonin levels in your brain. And help modulate cortisol levels produced in your adrenal glands. Helping you to cope with stress and lessen depression. Vitamin B5 (Pantothenic Acid) benefits When you take Vitamin B5 as a supplement, it is converted to pantethine. Pantethine is a more stable disulfide (double bonded) form of pantothenic acid. It is this active form of pantothenic acid that is converted into the enzyme Coenzyme-A (CoA). CoA plays a critical role in the metabolism and breakdown of the three essential micronutrients: proteins, carbohydrates, and fats. CoA is a cofactor in more than 70 enzymatic pathways including: • • • • • • •

Amino acid catabolism Acetylcholine synthesis Carbohydrate metabolism Fatty acid oxidation Heme synthesis Pyruvate degradation Phase II detox acetylation

CoA is also involved in the initial steps of cholesterol synthesis and all the downstream metabolites of cholesterol including steroid, Vitamin D and bile acids. CoA helps break down the carbon skeleton of amino acids which are metabolized to pyruvate and enter the KREBs cycle. This cycle is crucial to ATP synthesis within your mitochondria. CoA directs acetyl groups to form ubiquinone (CoQ10), squalene and cholesterol. You also need CoA for the transport of long chain fatty acids into mitochondria where fats are converted into energy. The bottom-line is CoA is behind the production of hemoglobin, bile, sex and adrenal hormones (steroids), cholesterol and the neurotransmitters acetylcholine and serotonin in your brain. How does Vitamin B5 (Pantothenic Acid) feel? Vitamin B5 is water-soluble and has been shown to improve mood, energy and cognition. Neurohackers who supplement with pantothenic acid report being wonderfully optimistic, energetic, and mentally sharp. People report Vitamin B5 helps them focus better, they feel a profound increase in energy and concentration improves. Many people dealing with acne find their skin looks great. Acne is cleared within a few days to a few weeks of supplementing with pantothenic acid.

Men and women find that supplementing with Vitamin B5 helps prevent hair loss. And if taken early enough may even help avoid hair turning prematurely gray. Some neurohackers report that pantothenic acid helps improve vision and hearing. The Research Vitamin B5 (Pantothenic Acid) reduces Acne 100 people of Chinese descent (45 males and 55 females) aged 10 – 30 years with severe acne were treated with high-dose pantothenic acid. A total of 10 grams per day were given in 4 divided doses. Participants were also asked to apply a cream to affected areas 4 – 6 times per day. The cream contained 20% pantothenic acid. Their face became noticeably less oily within 3 days of starting therapy. Within 2 weeks, facial pore size became smaller and acne lesions began to heal. And the rate of new acne eruptions had slowed. By 8 weeks, acne was usually controlled. Most acne lesions were gone and new eruptions occurred only occasionally. The participants with severe acne required 6 months of treatment to control acne. The author of the study noted that in some of the severe cases, daily doses of 15 – 20 grams of pantothenic acid would produce a faster response. 35 patients were monitored for 18 months; the maintenance dose needed to control acne ranged from 1 – 5 grams per day of pantothenic acid.1273 Vitamin B5 (Pantethine) to decrease LDL-Cholesterol User reviews consistently show success with lowering LDL-cholesterol and triglycerides and raising HDL-cholesterol by supplementing with Vitamin B5 (Pantethine). The National University of Health Sciences in Illinois conducted an evaluation of clinical trials from 1966 to 2002 for studies using the pantethine version of Vitamin B5 to improve cholesterol. 28 clinical trials with a pooled population of 646 ‘hyperlipidemic’ subjects were evaluated. Mean age of participants were 52.8 years. Average study length was 12.7 weeks with an average dosage of 900 mg per day of pantethine. The mean decrease of LDL-cholesterol (bad cholesterol) was 10 – 20%. The mean decrease of triglycerides was 14 – 33%. And the mean increase of HDL-cholesterol (good cholesterol) was 4 – 11%. The researchers concluded that “pantothenic acid was an effective therapeutic option in treating patient populations with total serum cholesterol levels greater than 200 mg/dL, and/or serum triacylglycerol levels greater than 150 mg/dL.” The team noted that the full benefit of pantethine may not be attained until at least 4 months from beginning supplementation. And that pantethine is a well-tolerated therapeutic agent that deserves much more attention than it has recently received.1274 Vitamin B5 (Pantothenic Acid) increases Longevity

Vitamin B5 is believed to extend life span. But research in humans for obvious reasons has been difficult. Humans live longer than most mammals. And tracking human subjects for life would be prohibitively expensive. So animal research is the next best thing. A team in Austin gave 33 young male and female mice 300 μg of calcium pantothenate daily in drinking water. Forty-one control mice did not receive the vitamin supplement. The mean life span for mice who received calcium pantothenate was 653.1 days. And for the control mice life span was 549.8 days. The mice using Vitamin B5 lived 19% longer.1275 Royal jelly has long been used as a longevity supplement. And some of the science backs this up. Pantothenic acid is the primary anti-aging factor isolated from royal jelly. The combination of pyridoxine, biotin and sodium yeast nucleate extended the lifespan of the common fruit fly. And the addition of pantothenic acid further increased life span.1276 Seems that supplementing with pantothenic acid (Vitamin B5) will help you live longer. Dosage Notes If you are using an acetylcholine (ACh) precursor like Alpha GPC or CDP Choline in your nootropic stack, you should be using Vitamin B5. Because B5 is needed to make Coenzyme-A (CoA). CoA and choline are needed to synthesize acetylcholine. The recommended dosage of Vitamin B5 (Pantothenic Acid) is a one-to-two ratio with a choline supplement. For example, 250 mg of Vitamin B5 with 500 mg of CDP Choline. If you don’t get enough Vitamin B5, you may not notice significant improvements when supplementing with your preferred choline source. If you’ve added choline to your racetam stack and still get a “choline headache” it’s likely because you don’t have adequate Vitamin B5 in your system. Pantothenic Acid or Pantethine is generally well tolerated in doses up to 1,200 mg/day. Some neurohackers report doses above 1,000 mg can induce gastrointestinal side effects like nausea or heartburn. Oral contraceptives (birth control pills) containing estrogen and progestin may increase the requirement for additional pantothenic acid. Use of Pantothenic Acid in combination with cholesterol-lowering drugs (statins) or with Vitamin B3 (niacin or nicotinic acid) may produce additive effects on blood lipids. So be careful because you could lower LDL-cholesterol to unhealthy levels. Side Effects Vitamin B5 (Pantothenic Acid) is non-toxic. So is considered well-tolerated and safe.

Side effects are rare but very high doses can include stomach upset, nausea or diarrhea. If you are taking the antibiotic tetracycline, you should avoid using extra Vitamin B5 because it could negate the effects of tetracycline. If you are on cholinesterase inhibitors used for treating Alzheimer’s, you should not be using Vitamin B5. Available Forms When choosing a Vitamin B5 supplement, your basic choice is between Pantethine or Pantothenic Acid. Pantethine is by far the more active choice when it comes to producing CoA. And this is backed up by many clinical trials. Researchers have pointed out that Pantethine creates twice as much CoA compared to Pantothenic Acid. However, Pantothenic acid does have its benefits. It enhances adrenal function and modulates inflammation. If you can, find a supplement that combines both. Vitamin B5 supplement labels will show pantothenic acid as “Calcium” or “sodium D-pantothenate” which is used for treating stress, migraines and allergies. Pantethine is mainly recommended for lowering blood cholesterol levels. And pantethine is better for stacking with a choline supplement because it creates more CoA than other forms of pantothenic acid. Pantothenol (panthenol) is a stable alcohol analog of Vitamin B5 (pantothenic acid), which can be rapidly converted to pantothenic acid by humans. Nootropics Expert® Recommendation Vitamin B5 (Pantothenic Acid) up to 1,000 mg per day I recommend using Vitamin B5 as a nootropic supplement. Your body does not make Vitamin B5 on its own. So to get its benefits you must get it from food or take it as a supplement. Vitamin B5 is especially helpful for those suffering from low energy levels, anxiety, depression, and chronic pain. Experience shows Vitamin B5 helps stop and reverse the symptoms associated with high cholesterol levels. B5 will lower ‘bad’ LDL-cholesterol and triglycerides as well as raise ‘good” HDL-cholesterol. Vitamin B5 is also particularly helpful to students and executives who want to boost cognition, learning and memory. Because it raises acetylcholine levels in your brain. Vitamin B5 can produce a noticeable increase in mental clarity. And give you a significant energy boost

physically and mentally. You’ll feel more awake and alert. Without the side effects you’d get from stimulants like caffeine. Vitamin B5 is a must have addition for any nootropic stack. If you are using any of the racetams like Piracetam and Aniracetam and are using a choline supplement to raise acetylcholine levels, you absolutely need extra pantothenic acid. The recommended dosage of Vitamin B5 (Pantothenic Acid) is a one-to-two ratio with a choline supplement. For example, 250 mg of Vitamin B5 with 500 mg of CDP Choline.

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Vitamin B6 (Pyridoxine) Vitamin B6 is known to enhance alertness, cognition, energy, elevate mood, lower anxiety and normalize homocysteine levels Vitamin B6 (Pyridoxine, Pyridoxal, Pyridoxamine) is one of 8 water-soluble B-vitamins that are absolutely vital to the highly optimized brain. And is essential to all forms of life. Vitamin B6 is found in every cell in your body and brain. Vitamin B6 is a necessary cofactor in the folate cycle. Vitamin B6 a required coenzyme for the synthesis of dopamine, epinephrine, GABA, melatonin, norepinephrine, and serotonin.1277 As a nootropic, Vitamin B6 is crucial for the synthesis of these neurotransmitters. Even mild deficiency results in down-regulation of GABA and serotonin synthesis. Leading to poor sleep, behavior, cardiovascular function, and the loss of hypothalamus-pituitary control of hormone secretion.1278 Vitamin B6 was first isolated in the 1930’s. The “6” in Vitamin B6 refers to six common forms, namely pyridoxal, pyridoxine (pyridoxol), pyridoxamine, and their phosphorylated forms. Pyridoxal phosphate (pyridoxal 5’-phosphate, P-5-P, PLP), the active form of Vitamin B6 is said to be the most versatile organic cofactor in biology. More than 140 distinct enzyme activities in your body and brain depend on PLP.1279 The biochemical reactions in your body by PLP-dependent enzymes include the making of hemoglobin, amino acid synthesis and fatty acid metabolism. PLP also functions as a coenzyme that catalyzes the release of glucose from stored glycogen. Turning it into the type of energy your brain cells can use for fuel. Pyridoxal phosphate helps control inflammation in your brain. Low levels of PLP are associated with severe inflammation in the brain.1280 Leading to neurodegenerative diseases like Alzheimer’s and Parkinson’s. And contributes to heart disease, arthritis, inflammatory bowel disease and diabetes. Vitamin B6 has a direct effect on your immune system, gene transcription and expression. And is involved in glucose regulation. Vitamin B6 protects your blood-brain barrier by regulating homocysteine levels. Excess homocysteine can damage blood vessel linings and neurons, resulting in cognitive decline. B6 also helps form myelin, the fatty sheath that surrounds and protects neurons. Foods rich in Vitamin B6 include bananas, beef, chickpeas, pistachios, pork, potatoes, and turkey. Even mild Vitamin B6 deficiency can deplete neurotransmitters which leads to cognitive decline. Resulting in brain fog, anxiety, depression and overall poor mental performance. How does Vitamin B6 (Pyridoxine) work in the Brain?

Vitamin B6 (Pyridoxine) boosts brain health and function in several ways. But two in particular stand out. 1. Vitamin B6 is a cofactor in neurotransmitter synthesis. Vitamin B6 and its role in amino acid metabolism makes it a critical component for the synthesis of all major neurotransmitters including dopamine, GABA, melatonin, norepinephrine and serotonin. The synthesis of these neurotransmitters is entirely dependent on B6 levels in your brain. Even mild deficiency results in less GABA and serotonin synthesis. Resulting in poor sleep patterns, irritability, anxiety, depression, panic attacks and stress. Low dopamine and norepinephrine levels due to lack of Vitamin B6 leads to depression and loss of memory. B-Vitamins play a crucial role in optimized cognition. And should be part of every nootropic stack. Unfortunately, there is very little talk in nootropic circles of these vitamins. A review of vitamin intakes in Germany, the UK, the Netherlands and the USA was conducted to compare vitamin intake to national recommendations. And the study found intake was below recommendations of even the most critical of vitamins. Including B-Vitamins. The authors of the study noted that this gap exists in vitamin intake and national recommendations for a significant portion of the population. Even though diverse foods were available.1281 2. Vitamin B6 helps reduce inflammation. B6 along with Vitamin B12 and folate help control homocysteine. High levels of homocysteine have been implicated in inflammation leading to damage of blood vessels. Causing heart and neurodegenerative disease. But homocysteine is not the bad guy when it’s in balance. We need this amino acid for the synthesis of cysteine which is a precursor to the master antioxidant glutathione. It’s when homocysteine gets out of control that causes problems in our brain and our cardiovascular system. One of the issues with aging is brain shrinkage. Gray matter shrinkage in key areas of the brain have been identified in Alzheimer’s Disease. Professor David Smith at Oxford University in England conducted a study with 156 elderly patients (age 70+) who were suffering mild memory loss and higher than average levels of homocysteine. High levels of homocysteine are typically the result of deficiencies in Vitamins B6, B12 and folic acid. For 2 years, the elderly patients received 20 mg of Vitamin B6, 0.5 mg of Vitamin B12 and 0.8 mg of folic acid (folate). The findings of this study were dramatic. Those who took only placebo experienced brain atrophy of 5.6% over those 2 years. Brain shrinkage in those who took the B-Vitamins had only 0.6% brain shrinkage. This study showed a 7-fold difference in gray matter shrinkage in just 2 years. Vitamin B6 along with B12 and folic acid helped protect brain density. And specifically in the areas of the brain vulnerable to

Alzheimer’s.1282 How things go bad Vitamin B6 deficiency is a lot more common than you’d expect in our modern society. B6 from diet alone, especially for vegetarians and the aged is not adequate to supply what our body and brain needs. ↓ Concentration, memory, learning, and recall decline ↑ Anxiety, confusion, irritability, and depression increase ↑ Homocysteine and inflammation increases ↓ Energy levels decline Vitamin B6 is critical for nerve function. And a deficiency can result in psychiatric disorders, seizures, migraines, chronic pain and mood disorders like depression. Vitamin B6 (Pyridoxine) benefits Vitamin B6 is involved in the regulation of cognition function and mood. B6 is a cofactor in the neurotransmitters directly related to alertness, anxiety, attention, concentration, memory and mood.1283 When you add Phenylalanine to your stack to boost the neurotransmitters dopamine, epinephrine, norepinephrine and melatonin, it will not work without Vitamin B6. B6 is a critical cofactor in the synthesis of these neurotransmitters. The same holds true for any nootropic you use with the intention of boosting any of the major neurotransmitters in your brain. Vitamin B6 is absolutely required if you want them to do their job. You need Vitamin B6 to help control inflammation in your brain. B6 suppresses the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).1284 Vitamin B6 is essential for controlling elevated homocysteine levels which can damage blood vessels crucial for optimal cerebral circulation. A 2008 review of research in the previous 10 years covering a total of 77 studies and 34,000 subjects demonstrated the relationship between cognitive deficits and dementia and the status of folate, or vitamins B12, or B6 and homocysteine levels.1285 Vitamin B6 is a coenzyme involved in the synthesis of Heme, an iron-containing component of hemoglobin. Hemoglobin is found in red blood cells and is critical to their ability to transport oxygen throughout your body and brain. Vitamin B6 concentrations in your brain are about 100-times higher than levels in your blood. B6 is critical to the highly optimized brain. How does Vitamin B6 (Pyridoxine) feel?

Vitamin B6 is water-soluble and has been shown to improve energy and mood. Both men and women report a boost in libido when supplementing with B6. Women report that Vitamin B6 helps control mood swings resulting from PMS. Neurohackers report that Vitamin B6 helps sleep and creates vivid dreams. Many prefer it over melatonin for sleep. Those suffering with carpal tunnel syndrome have consistently found relief in symptoms by using Vitamin B6. Many find B6 useful for tendonitis and other joint pain. Some report that supplementing with Vitamin B6 helps prevent sunburn. And a few have found relief from tinnitus by using B6. Those dealing with ADHD have found that using Vitamin B6 has helped reduce the reliance on ADHD meds. Likely because B6 is a cofactor in the synthesis of dopamine and norepinephrine. The Research Vitamin B6 (Pyridoxine) promotes vivid dreams Read the reviews of those supplementing with Vitamin B6 and you’ll come across several reports of improved sleep and vivid dreams. And we have science to back this up. 12 college students participated in a double-blind, placebo-controlled trial to examine the various claims that Vitamin B6 increase dream vividness, and the ability to recall dreams. The students were given 100 or 250 mg of Vitamin B6 or a placebo prior to bedtime for 5 consecutive days. Morning reports indicated a significant difference in ‘dream-salience scores’. This is a composite score measuring dream vividness, bizarreness, emotionality, and color. The study suggests that Vitamin B6 may act by increasing arousal during rapid eye movement (REM) sleep. The researchers hypothesized it had something to do with the conversion of tryptophan to serotonin.1286 Vitamin B6 (Pyridoxine) may prevent Parkinson’s Disease A study out of the Netherlands suggests that Vitamin B6 could cut the risk of Parkinson’s Disease in half. Researchers in Rotterdam recruited 5,289 people over the age of 55 and assessed their dietary intake using food questionnaires. This study looked into reports that increased levels of the amino acid homocysteine may promote Parkinson’s Disease. Numerous studies have reported that higher intakes of folate, Vitamin B12 and Vitamin B6 decrease blood homocysteine levels and could offer protection from Parkinson’s. It has also been proposed that Vitamin B6 could provide antioxidant effects. And could reduce the risk

factor for Parkinson’s by a mechanism that is not related to homocysteine. After 9.7 years of follow-up, 72 new cases of Parkinson’s Disease had been diagnosed. The average Vitamin B6 intake was 1.63 mg per day, average B12 intake was 5.3 mcg per day, and average folate intake was 218.7 mcg per day. No significant reductions in the risk of Parkinson’s were found for folate or Vitamin B12. But when the researchers limited their calculations to the 66% of participants who were smokers, they found that the protective effects of high Vitamin B6 intake appeared limited to this group. The researchers noted that several studies indicate the protective effects of nicotine on brain cells and reduced the risk of Parkinson’s. Which suggests that Vitamin B6 plus nicotine provides mutually reinforcing beneficial effects. Since folate and Vitamin B12 showed no relationship to reduced Parkinson’s, the researchers concluded it was not homocysteine that was behind the newly diagnosed patients. The study authors said that the apparent benefits of B6, “may point towards an alternative mechanism… because several lines of evidence suggest neuroprotective properties of Vitamin B6 through antioxidant capacities”. Oxidative stress has been shown to be prominent in Parkinson’s Disease, and higher Vitamin B6 intake may reduce Parkinson’s risk through its antioxidant effects.1287 Vitamin B6 (Pyridoxine) to beat Panic Attacks Reduced serotonin levels are known as one of the causes of panic attacks and hyperventilation attacks. Serotonin is synthesized from tryptophan. And for the synthesis of serotonin, you need Vitamin B6 and iron. The clarify how this works, researchers at Atago Hospital in Japan checked the blood levels (vitamins B2, B6, and B12 and iron) of patients who came into the ER with a panic attack or hyperventilation attack. The team measured parameters in 21 patients compared to 20 healthy volunteers. The study found that both Vitamin B6 and iron levels were significantly lower in the panic and hyperventilation attack people than in the healthy volunteers. There was no significant difference in Vitamin B2 or B12. The study concluded that low blood concentrations of Vitamin B6 and iron are involved in panic and hyperventilation attacks.1288 Dosage Notes Recommended dosage of pyridoxal 5’-phosphate (P-5-P) form of Vitamin B6 is up to 100 mg per day. P-5-P is the only ‘active’ form of B6 available and preferred for nootropic usage. (see “Side Effects” for toxicity with regular Vitamin B6).

The enzyme L-dopa decarboxylase depends on P-5-P to convert L-DOPA into dopamine. And is involved in the final stages of serotonin synthesis.1289 An analysis of data collected in the USA in 2003-2004 indicated that Vitamin B6 intake from food averaged about 1.9 mg per day.1290 The problem is some forms of Vitamin B6 from plants (pyridoxine glucoside) are not very bioavailable. In most cases, and certainly that of neurohackers using nootropics to boost neurotransmitters or improve mood, Vitamin B6 from diet alone is not enough. The study mentioned above shows that even those supplementing with 2 mg per day of Vitamin B6 or less had blood levels of B6 much too low. Vitamin B6 is water-soluble and you excrete it in urine, so supplementation daily is critical. Women taking birth control pills, or who are menstruating are usually low in Vitamin B6. Those following a strict vegetarian diet are also typically deficient in B6. Drugs like L-DOPA, anti-tuberculosis medications, metal chelators, methylxanthines to treat respiratory conditions, and long-term use of NSAIDs, anti-convulsants, and phenobarbital all inhibit Vitamin B6 metabolism. If you are using any of these drugs you are likely low in B6. You can safely dose up to 100 mg per day of Vitamin B6 with no toxic effects. Side Effects Vitamin B6 (Pyridoxine) is non-toxic at recommended doses. So is considered well-tolerated and safe. Side effects are rare but very high single doses can include stomach upset, nausea or diarrhea. Pyridoxine neuropathy is a form of nerve damage caused by high doses of Vitamin B6 when taken for extended periods. Symptoms are loss of coordination, extreme skin sensitivity, bone pain, muscle weakness, and numbness. Pyridoxine neuropathy has been reported in doses of Vitamin B6 of 200 mg to 5 grams per day for extended periods. When dosing was stopped, symptoms usually disappeared.1291, 1292 This nerve damage has been identified as the destruction of axons and neurons which is reversible at lower levels of toxicity. And irreversible at higher levels of Vitamin B6 toxicity.1293, 1294 Available Forms Vitamin B6 from food and supplements comes in the form of Pyridoxine, Pyridoxal, and Pyridoxamine. These forms of B6 are considered ‘inactive’ but are converted in your liver and intestines into the active form of Vitamin B6 called pyridoxal 5’-phosphate (P-5-P).

For nootropic use, look for a P-5-P supplement or a B-Complex formula that uses P-5-P. Nootropics Expert® Recommendation Vitamin B6 as pyridoxal 5’-phosphate (P-5-P) up to 100 mg per day I recommend using Vitamin B6 as a nootropic supplement. Your body does not make Vitamin B6 on its own. So to get its benefits you must get it from food or take it as a supplement. Vitamin B6 is especially helpful for those suffering from low energy levels, anxiety, depression, and chronic pain. Experience shows Vitamin B6 helps stop and reverse the symptoms associated with high homocysteine levels. B6 in combination with folic acid and Vitamin B12 will lower high homocysteine implicated in heart disease and Alzheimer’s. Vitamin B6 is also particularly helpful to students and executives who want to boost cognition, learning, memory and mood. Because it raises dopamine, GABA, norepinephrine, epinephrine and serotonin levels in your brain. Vitamin B6 can help those dealing with ADHD because it helps synthesize dopamine and serotonin in your brain. ADHD symptoms should decline, and you may be able to cut back on your ADHD meds. Vitamin B6 is a must have addition for any nootropic stack. If you are using any nootropics to raise dopamine, GABA or serotonin levels, you absolutely need extra Vitamin B6.

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Vitamin B8 (Inositol) Vitamin B8 is known to decrease anxiety, depression, panic attacks, mood swings, ObsessiveCompulsive Disorder and alleviate the symptoms causing bulimia Vitamin B8 (Inositol, cyclohexanehexol) is a sugar alcohol and isomer of glucose. As a nootropic, inositol is involved in brain cell signaling, and is a component of cell membranes. Vitamin B8 is no longer considered a ‘true’ B-Vitamin because your body can make inositol on its own. A “true vitamin” is either essential for life and/or cannot be made by the human body. So inositol no longer qualifies. Inositol is used in your brain as a “secondary messenger”. It facilitates communication between brain cells. All of your major neurotransmitters need inositol to relay messages. Inositol is also a component making up the phospholipid ‘shell’ encasing each brain cell. Once again, inositol acts as a messenger of sorts by assisting in the transport of amino acids, proteins and neurotransmitters across and into the brain cell. Inositol is a ‘group’ of 9 molecules called ‘stereoisomers’. Myo-inositol is the most abundant stereoisomer, making up 90-95% of the total free inositol in your body. As a nootropic, Vitamin B8 (Inositol) can be used to treat panic attacks and anxiety, depression, Obsessive Compulsive Disorder (OCD), bulimia, depression in bipolar disorder and mood swings. Myo-inositol is involved in cell-signaling. In the simplest terms, myo-inositol hears from the first neuron that it’s about to fire over a neurotransmitter. And passes that information on to the receiving neuron. Not enough inositol and the neurotransmitter can’t do its job. Inositol is one busy molecule in your body: • • • • • • •

Myo-inositol affects mRNA which regulates cell volume.1295 Phosphatidylinositol signaling pathways control signals inside and outside of brain cells.1296 Inositol plays a role in DNA repair1297 Inositol affects long-term potentiation1298 Myo-inositol is a component of cell membranes Myo-inositol regulates cell metabolism Myo-inositol regulates cell energy consumption

How does Vitamin B8 (Inositol) work in the Brain? Vitamin B8 (Inositol) boosts brain health and function in several ways. But two in particular stand out. 1. Inositol influences neuroplasticity and neurotransmitters. Transcranial Direct Current Stimulation (tDCS) has been used to treat depression, Parkinson’s Disease, stroke and pain. But the maximum effect of tDCS in the brain was not until several minutes after treatment. Which

indicates the effects of tDCS is not by direct neurotransmitter action like you would expect for example if you were using a nootropic.1299 Researchers concluded the effect of tDCS was best explained by the activation of a ‘secondary messenger system’, and modulation of brain cell membrane proteins. Neurotransmitters, neuromodulators, and hormones have been shown to exert their action via an intracellular (inside the cell) secondary messenger system in which the activated neuroreceptor stimulates the turnover of inositol phospholipids.1300 Clinical studies have found that low levels of inositol are present in patients with anorexia, brain disorders and depression.1301 And abnormal levels of myo-inositol in middle-aged adults can signal the initial stages of cognitive decline such as Alzheimer’s and dementia.1302 2. Inositol helps reduce anxiety and depression. Long-term potentiation needed for encoding long-term memories, and long-term depression, rely on neural signal transmission and synaptic plasticity. And both are strongly influenced by the myo-inositol and phosphoinositide pathway.1303 A meta-analysis and systematic review of clinical studies were evaluated comparing inositol for depression and anxiety disorders. The researchers concluded that inositol was beneficial for treating depression and anxiety.1304 How things go bad Inositol is an important component of brain cell membranes. And is critical as a secondary messenger for both intra- and extra-cellular signaling. Low inositol levels have been found in those with major depressive disorder, Alzheimer’s, Parkinson’s and other neurodegenerative diseases. Science does not yet know if low inositol is a result of or contributes to these diseases. ↓ Inositol levels decline ↓ Serotonin and dopamine receptor density declines ↓ Anxiety and depression get worse ↓ Concentration, cognition and memory decline ↑ LDL-cholesterol (bad) and triglycerides increase ↓ HDL-cholesterol (good) levels decline ↑ Inflammation and oxidative stress damage neurons Vitamin B8 supplementation can help increase the density of serotonin and dopamine receptors in your brain. And improve neurotransmitter signaling. Helping you to cope with stress, lessen depression and improve memory.

Vitamin B8 (Inositol) benefits Myo-inositol enhances serotonin neuroreceptor sensitivity.1305 And several studies have proposed a SSRI-like role for myo-inositol. Researchers believe inositol works as a SSRI because it is a secondary messenger of serotonin. In other words, inositol gets a message from the 1st neuron that says it wants to send over a serotonin molecule. Inositol picks up that message and lets the receiving neuroreceptor know there’s an incoming serotonin molecule. Serotonin signaling is fixed and depression goes away.1306 In some regions of your brain, serotonin acts more like a “neuromodulator” rather than a “classic” neurotransmitter. And can affect glutamate and GABA as well.1307 Inositol as a secondary messenger, is an integral part of neuroplasticity and neurotransmitter signaling. Affecting anxiety, alertness, concentration, cognition, depression and all forms of memory. A large percentage of patients do not respond to SSRI’s when used to treat depression or anxiety. The problem could be depression not related to serotonin or GABA deficiency (they could have a dopamine problem instead). But if it is serotonin-related depression and there is no response to SSRI’s, inositol may help. Myoinositol helps relay the messages sent and received by serotonin receptors. Another problem with SSRI’s like lithium is Serotonin Syndrome. Too much serotonin can be released in the brain which can be toxic and deadly. Or the SSRI can deplete stores of inositol which raises serotonin levels too high. Once again, inositol comes benefits. Researchers found that myo-inositol + lithium alleviated Serotonin Syndrome.1308 Myo-inositol regulates blood sodium levels which helps in the maintenance of healthy myelin sheaths that protect neurons. Myo-inositol protects your brain from a leaky blood-brain barrier that if left unchecked, would allow toxins produced in your liver to enter your brain.1309 Inositol can relieve anxiety and Obsessive-Compulsive Disorder (OCD). Myo-inositol can reduce panic attacks. And inositol can reduce mood swings. Studies show that inositol is as effective as SSRI’s in treating the symptoms of bulimia and binge eating.1310 Inositol can protect against lung cancer caused by smoking.1311 Myo-inositol increases sperm concentration, total sperm count, decreases follicle stimulating hormone and luteinizing hormone in infertile males.1312 Myo-inositol can help lower LDL-cholesterol (bad-cholesterol), C-reactive protein and blood glucose

levels while increasing HDL-cholesterol (good cholesterol).1313 Inositol reduces inflammation. Phosphatidylinositol reduces pro-inflammatory cytokines.1314 And Dchiro-inositol decreases the mRNA expression and secretion of tumor necrosis factor-α, interleukin 6 (IL-6).1315 D-chiro-inositol has anti-aging properties and can extend lifespan.1316 The bottom-line is inositol is a potent pseudo-vitamin and can be a great compliment to any nootropic stack. How does Vitamin B8 (Inositol) feel? Inositol makes it easier to fall asleep. Unlike other sleep-inducing nootropics or sleep meds, it doesn’t “knock you out”. Falling asleep is just effortless. Inositol increases serotonin and dopamine receptor densities. So damage that you may have done to dopamine receptors are repaired (particularly an issue with ADHD stimulant meds). And serotonin is simply more effective. Anxiety decreases, motivation goes up and depression goes away. Inositol is great for social occasions because anxiety levels decrease. In fact, inositol outperformed fluoxetine (Prozac®) at reducing panic attacks and can become effective in just a few days. With no side effects. Some neurohackers feel that supplementing with inositol is the best anti-depressant they’ve every used. The real beauty of inositol is you can safely combine it with the current antidepressant (i.e. SSRI) medication you currently take. Your antidepressant meds may work better! Inositol is a proven remedy for treating the symptoms of Obsessive-Compulsive Disorder (OCD). You should feel a noticeable reduction in negative thoughts. Some things just won’t bother you as much. And won’t dominate your thoughts so easily. And inositol is an effective method of taming panic attacks. The Research Inositol to Treat Panic Attacks Estimates are that only about 70% of patients respond to standard drug treatments for panic disorder. And many often discontinue the drugs because of negative side effects. Israeli researchers decided to compare inositol with the SSRI fluvoxamine (Luvox®) for panic disorder. In this double-blind, controlled, random-order crossover study 20 patients completed 1 month of 18 grams per day of inositol and 1 month of 150 mg per day of fluvoxamine. In the first month, inositol reduced the number of panic attacks per week by 4 compared to only 2.4 for fluvoxamine. Nausea and fatigue were noted with those using Luvox® but not with inositol. The natural compound inositol was more effective than a SSRI for treating panic disorder.1317

Vitamin B8 (Inositol) for Depression A study published in the American Journal of Psychiatry noted that levels of inositol in depressed patients were lower than normal. In this trial, the authors administered 12 grams per day of inositol or a placebo to depressed patients for 4 weeks. The overall improvement in depression scores was significantly greater than placebo by week 4. And no side effects were noted. The researchers commented that “this is the first time a precursor strategy for a secondary messenger rather a neurotransmitter” was used in treating depression. The authors concluded that “inositol had a significant antidepressant effect”.1318 Another study tried using inositol to treat Premenstrual Dysphoric Disorder (PMDD). PMDD is a particularly nasty form of PMS. It’s a condition in which a woman has severe depression, irritability and tension before menstruation. Scientists don’t really know what causes PMDD except it has something to do with serotonin. Serotonin is the “calming neurotransmitter”. When it fails for any reason you get depressed, irritable, obsessive, negative and worried. In this 2-phase clinical trial, PMDD patients were given myo-inositol in powder form, or a soft-gel capsule equivalent to 2 grams of myo-inositol. The results showed a significant improvement on 3 different scales of measuring depression. Inositol significantly improved PMDD and associated depression, irritability and tension.1319 Vitamin B8 (Inositol) for OCD Inositol is good for treating Obsessive-Compulsive Disorder (OCD). OCD is a type of anxiety characterized by unwanted, recurring thoughts and behaviors. One double-blind, controlled crossover trial treated 13 OCD patients with 18 grams per day of inositol for 6 weeks. The OCD patients had significantly lower scores on the Yale-Brown Obsessive Compulsive Scale when taking inositol than when taking placebo. The authors concluded that “inositol is effective in depression, panic, and obsessive-compulsive disorder, a spectrum of disorders responsive to selective serotonin reuptake inhibitors (SSRI’s)”.1320 Dosage Notes Recommended dosage for inositol is up to 3 grams per day. Typically split into 3-doses of 1 gram each. One in the morning, one at noon, and your final dose before bedtime. Clinically effective dosage for depression and anxiety is up to 12 grams per day. Split your dose into 3times per day. 4 grams in the morning, 4 grams at noon and 4 grams prior to bedtime.

Clinically effective dosage for OCD is up to 18 grams per day. Split into 3 equal doses of 6 grams each. The clinical dosages mentioned here are the ones used in clinical trials. Most people experienced relief of symptoms within 3 months. Some people showed improvements within a week or sooner. Important note: It should not be necessary for you to go as high as 12 or 18 grams per day. Inositol should be just as effective for you in much smaller doses. Most neurohackers notice benefits when taking 3 – 4 grams per day or less. Side Effects Vitamin B8 (Inositol) is non-toxic. So is considered well-tolerated and safe. Higher doses like those used in clinical trials could result in flatulence, stomach upset, nausea, diarrhea, increased mood swings for bipolar or psychosis patients. If you’ve been diagnosed with bipolar or bipolar-spectrum disorder, please consult a pharmacist or your doctor before using inositol. Studies have shown and neurohackers verify that inositol supplementation may reduce testosterone levels and libido. Most of the Low-T reports were by woman but I’ve heard a few men reporting Low-T and libido from inositol as well. Available Forms Inositol is available in capsules, softgels, and in powder form. Inositol powder is the least expensive way to supplement with this nootropic. Inositol is basically a sugar, so it tastes sweet. Not as sweet as sugar but it tastes good on its own. Or mixed in your favorite beverage. Lecithin is comprised of both inositol and choline. So lecithin as a supplement will provide you with inositol. Inositol is often supplied by supplement manufacturers as “inositol + choline”. The thinking behind this combined supplement is that inositol compliments the effects of choline. When inositol and choline are used together, they are supposed to improve nerve function and help you metabolize cholesterol. But high doses of choline can leave you depressed and sleepy. So if you want to add inositol to your nootropic stack, I suggest you avoid the combination and go with straight inositol. Nootropics Expert® Recommendation Vitamin B8 (Inositol) up to 3 grams per day I recommend using Vitamin B8 (Inositol) as a nootropic supplement.

Your body does make Vitamin B8 on its own. And you get it from food. So it is unlikely that you are inositol deficient. But if you want to try inositol for its anti-anxiety and antidepressant benefits, you must take it as a supplement. Inositol is especially helpful for those suffering from anxiety, depression, panic attacks, or OCD. Experience shows Inositol helps stop and reverse the symptoms associated with high cholesterol levels. B8 will lower ‘bad’ LDL-cholesterol as well as raise ‘good” HDL-cholesterol. Vitamin B8 is also particularly helpful to quell anxiety caused by social situations. Vitamin B8 can help you get a good night’s sleep. Many find it more effective than sleep meds and other nootropics used for sleep. You’ll awaken feeling refreshed and calm. Ready to start your day. The recommended dosage of Vitamin B8 (Inositol) is up to 3 grams per day. But start at a gram or less and work your way up depending on how you feel. Clinical doses of 12 or 18 gram are usually not needed for most people.

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Vitamin B9 (Folate) Vitamin B9 is known to improve mood, energy, initiative, alertness, concentration, psychomotor speed, and social activity Vitamin B9 (Folate, folic acid, 5-methylenetetrahydrofolate) is water-soluble, and one of 8 B-Vitamins. Folate functions as a coenzyme in single-carbon transfers in the synthesis of DNA and RNA. And converts homocysteine to methionine which is used in the synthesis of S-Adenosyl-methionine (SAMe).1321 As a nootropic, folate is also involved in gene expression, amino acid synthesis, myelin synthesis, and is required for the synthesis of the neurotransmitters dopamine, epinephrine, norepinephrine and serotonin. Many neurohackers, including doctors and other health professionals confuse folate with folic acid. They are NOT the same. In this chapter, we’ll explore the differences between folate and folic acid. And how Vitamin B9 (folate) is critical for the fully optimized brain. Folate is used in red blood cell production, helps break down and use proteins, and just about every other process in your body. Folate deficiency is found in at least a third of those suffering from depression. Folate touches nearly everything happening in your brain. And the reason why we’re investigating it here. Folate should be part of your nootropic stack. Green leafy vegetables, or ‘foliage’ are rich sources of folate. And how ‘folate’ got its name. You can also get folate from citrus fruit juice, legumes, fortified foods and liver. When you eat vegetables containing folate, or eat flour-enriched with folic acid, an enzyme called MTHFR (5,10-methylenetetrahydrofolate reductase) converts folic acid and food folate into 5methylenetetrahydrofolate (methyl-folate or 5-MTHF). Folate is a general term for a group of various tetrahydrofolate (THF) derivatives naturally found in food. Folic acid refers to an oxidized synthetic compound used in dietary supplements and food fortification. THF can enter the main and natural folate metabolic cycle which starts out in the mucosa of your small intestine. Synthetic folic acid on the other hand undergoes initial reduction and methylation in your liver, where conversion to the THF form requires the enzyme dihydrofolate reductase. One of the problems with choosing the unnatural folic acid version is if there is low activity of the dihydrofolate reductase enzyme, combined with high intake of folic acid, you end up with unnatural levels of unmetabolized folic acid entering your circulation.

Several studies have reported the presence of this unmetabolized folic acid in blood following consumption of folic acid supplements, or folic acid-fortified food.1322 We have growing evidence in Western society that we generally test for excess levels of unnatural folic acid. Due mainly to eating processed foods and folic acid-enriched flour. And still suffer from a folate deficiency. High doses of synthetic folic acid may increase your risk of cancer, immune system damage and other health problems.1323 Problems with MTHFR Another major problem affecting folate deficiency is problems with the MTHFR gene. Remember that this enzyme called MTHFR (5,10-methylenetetrahydrofolate reductase) is needed to convert folic acid and food folate into 5-methylenetetrahydrofolate. There are two common variants in this gene that affects the functioning of MTHFR. They are called C677T and A1298C. Both variants are genetically inherited. And depending on their presence in your system, can reduce the effectiveness of MTHFR from 30 – 70%. Another cause for folate deficiency. Estimates of the prevalence of these mutations in our general population are up to 60%. Some doctors report that nearly every patient in their practice have one or both MTHFR mutations.1324 And we have clinical evidence of the association between both MTHFR mutations in depression, bipolar disorder, and schizophrenia.1325 Folate is one busy molecule in your body: •

• • • •

Donates a methyl group to homocysteine to make SAMe. The methyl donor SAMe is involved in the formation of phospholipids, glutathione, myelin, coenzyme Q10, carnitine and creatine in your brain Synthesizes the enzyme cofactor biopterin (BH4) which is critical for the synthesis of major neurotransmitters including dopamine, epinephrine, norepinephrine and serotonin Synthesizes DNA and tRNA Recycles and reduces the inflammatory amino acid homocysteine Builds red and white blood cells and platelets.

How does Vitamin B9 (Folate) work in the Brain? Vitamin B9 (Folate) boosts brain health and function in several ways. But two in particular stand out. 1. Folate influences neuroplasticity and neurotransmitters. Folate is required for the synthesis of the neurotransmitters dopamine, epinephrine, and serotonin. The active metabolite of folate, 5-methyltetrahydrofolate (5-MTHF, L-Methylfolate), participates in remethylation of the amino acid homocysteine, creating methionine. S-adenosylmethionine (SAMe), the downstream metabolite of methionine, is involved in numerous biochemical methyl donation reactions,

including reactions forming the above-mentioned neurotransmitters. Without the participation of 5-MTHF in this process, SAMe and neurotransmitter levels decrease in the cerebrospinal fluid, contributing to the disease process of depression. Studies have shown that those being treated for depression with SSRI antidepressants, and not responding to these drugs, can get a much better response by taking folate with their antidepressants.1326 2. Folate helps reduce depression. Folate is involved in one-carbon metabolism in the brain. This folate cycle is responsible for the synthesis of methyl groups, which are utilized by SAMe in several methylation reactions involving nucleoproteins, proteins, phospholipids, neurotransmitters, and monoamines. Deficiency of both folate and Vitamin B12 will impair methylation processes. Causing the accumulation of homocysteine. Low concentrations of folate in your blood, red blood cells and cerebrospinal fluid are associated with depression and dementia. Research shows that cognitive function is related to methylation processes in your brain.1327 This depression hypothesis is supported by the similar effect of SAMe on monoamine metabolism, which is also implicated in depression.1328 The lowest concentrations of folate and SAMe in cerebrospinal fluid are found in dementia, including Alzheimer’s Disease.1329 How things go bad Methyl-folate (5-MTHF) works with Vitamins B2, B6 and B12 as well as cofactors like magnesium in this methylation cycle in every cell in your body and brain. The metabolic process called methylation occurs when one molecule provides a methyl group, which is a carbon atom linked to three hydrogen atoms, to another molecule. And makes things like creatine, carnitine, CoQ10, phosphatidylcholine (PC), melatonin and a bunch of other crucial neurotransmitters and substances in your body. Methylation is involved in cognition, repairing DNA, turning genes on and off, fighting infections and inflammation, getting rid of toxins and much, much more. Problems with methylation (which can be caused by not enough folate) can contribute to addictions, Alzheimer’s, anxiety, ADD and ADHD, bipolar and manic depression, chronic fatigue syndrome, dementia, diabetes, fibromyalgia, schizophrenia, and hypothyroidism. Methylation is not only involved in the synthesis of neurotransmitters but breaking them down as well. This critical step, when broken, causes a buildup of neurotransmitters that can lead to seizures, insomnia, panic attacks, fits of rage, and more. Much more. A deficiency of methyl-folate (5-MTHF) in your body caused by problems with this methylation pathway leads to a deficiency of glutathione, your major antioxidant. This can take shape as

fibromyalgia, chronic fatigue, increased immune activation, chemical sensitivities and even diseases like ALS, MS, and Parkinson’s. Not enough folate and you can experience: ↓ Mitochondrial dysfunction1330 ↓ Depression, mood and social function decline ↓ Cognitive function declines ↓ Concentration, cognition and memory decline ↑ Risk of Alzheimer’s and dementia increase ↑ Risk of anemia increases ↑ Irritability, forgetfulness, and mental sluggishness increase Vitamin B9 supplementation can help increase the density of serotonin and dopamine neurotransmitters in your brain. And improve neurotransmitter signaling. Helping you to cope with stress, lessen depression and improve memory. Vitamin B9 (Folate) benefits Depression affects about a quarter of the US population who will have at least one depressive episode in their lifetime. (My apologies to our readers from other countries. I only have statistics for the USA). But world-wide, folate deficiency is found in at least a third of those suffering from depression. And research shows that folate levels even in the “normal range” might be inadequate for methyl donation and neurotransmitter synthesis. By adding folate, or methyl-folate to your nootropic stack, you’re adding a necessary ingredient for the synthesis of the neurotransmitters dopamine, epinephrine, norepinephrine and serotonin. The active metabolite of folate (5-MTHF, L-methyl-folate) participates in the re-methylation of the amino acid homocysteine creating methionine. SAMe, the downstream metabolite of methionine, is involved in several methyl donor reactions, including forming most of your major neurotransmitters. Methyl-folate also seems to save the day by stepping in, and substituting for tetrahydrobiopterin (BH4), an essential cofactor in neurotransmitter synthesis (when BH4 is low). The bottom-line: folate helps boost alertness, attention, cognition, memory, and mood. And helps alleviate brain fog, anxiety and depression. How does Vitamin B9 (Folate) feel? Up to 60% of us do not produce enough of the enzyme needed to break down the synthetic folic acid found in supplements and fortified foods like breakfast cereal and bread. And the simple presence of

this impostor in our diet is likely contributing to many of our modern diseases. Neurohackers report that dosing with methyl-folate: • • • • • • • • •

Boosts alertness and energy levels Relief from chronic pain Tolerance for heat increases Sociability increases Relief from depression, fatigue and paranoia Fewer headaches Mental clarity increases Much happier, calmer, more energetic Gingivitis and gum inflammation decreases

The Research Folate as an Antidepressant Many who use antidepressants experience little to no relief in depressive symptoms. And researchers set out to find out why antidepressant meds were not working. Dr. Jerome Sarris of the University of Melbourne decided to do a meta-analysis of clinical trials using ‘nutrients’ along with antidepressants in PubMed, CINAHL, Cochrane Library, and Web of Science up to 2015. The research team found that Omega-3’s combined with antidepressants boosted the success of using these meds for depression. The team also found strong evidence for methyl folate, Vitamin D, and SAMe. The research showed that using folic acid or inositol provided no benefit. The team concluded there was strong evidence for using methyl folate, Omega-3, Vitamin D and SAMe with antidepressants to reduce depression.1331 Another study in Milan compared using methyl-folate with the antidepressant Trazadone. 96 patients with dementia received either 50 mg of methyl-folate per day, or 100 mg of Trazadone. After 4 weeks of treatment, depression scores for the methyl-folate patients decreased more than for the Trazadone patients.1332 Folate Reduces Risk for Dementia Folate deficiency is associated with a tripling in the risk of developing dementia among elderly people. Researchers tracked 518 people over the age of 65 for 2 years for dementia development. The study found that the onset of dementia was much more likely in those whose folate levels fell over 2 years.1333 Another study published in the British Medical Journal looked at the neurological status of 24 folatedeficient patients compared with a control group of 21 normal folate-level patients.

The study showed a significant increase in organic brain syndrome in the folate-deficient group.1334 Organic brain syndrome is a general term used to describe decreased mental function caused by something other than psychiatric illness. Vitamin B9 (Folic Acid) Improves Memory A study published in the Journal of the American Medical Association evaluated nutritional status and cognitive function in 260 men and women older than 60 years. The study showed there was a significant relation between impaired abstract thinking ability and memory, and lower folate levels and intake.1335 In another open study of 38 folate deficient subjects with depression, lethargy, and memory impairment, 50 mg of folinic acid per week for 120 days significantly improved visuomotor performance, visuospatial memory, logical reasoning, associative memory, and activities for daily living.1336 Dosage Notes Recommended dosage for Vitamin B9 (Folate) is 500 mcg. If you decide to add folate to your nootropic stack, start with B12 in the form of methylcobalamin. And then introduce your dose of methyl-folate and cofactors such as Vitamin B2, Vitamin B3, Vitamin B6, trimethyl glycine, and Vitamin C If you have an adverse reaction to methyl-folate (agitation, increased anxiety, headache), you can take Vitamin B3 (nicotinic acid or niacinamide) in 50 mg dosages every 30 minutes until you experience relief. Note that Vitamin B3 (niacin) requires SAMe for its metabolism. And can contribute to a drop in methylation if you’re low in SAMe. It is also a cofactor for the enzyme COMT that breaks down norepinephrine, epinephrine, and estrogen, which are all potentially elevated if you are experiencing anxiety. Side Effects Vitamin B9 (Folate) is non-toxic. So is considered well-tolerated and safe. But note that higher doses of Vitamin B9 like those used in clinical trials nearly always use synthetic folic acid. If you are deficient in Vitamin B12, and many people are, can manifest as anemia. And is undisguisable from folate deficiency. Large doses of folate could correct anemia. Without correcting the underlying B12 deficiency. And leave you at risk for irreversible brain damage. This is why the US Institute of Medicine advises that all adults limit their intake of folic acid supplements to 1 mg daily. Note that it is unlikely that you’ll encounter this problem by using folate or methyl-folate instead of folic

acid. But we don’t have the science yet to back this claim up. High concentrations of unmetabolized folic acid in your blood, especially if you’re low in Vitamin B12, could result in a compromised immune system. And problems with cognition. Other side effects of using folic acid, particularly in high doses include stomach problems, insomnia, skin reactions, confusion, loss of appetite, nausea and seizures. Many medications interfere with folic acid absorption including antibiotics, Dilantin, Daraprim, chemo meds, antacids, proton pump inhibitors, anti-seizure medications, NSAIDS (ibuprofen and naproxen), Azulfidine, and Methotrexate. Available Forms Vitamin B9 (Folate) is available in capsules, softgels, and in powder form. Studies have shown that the active form of folate, methyl-folate, which is more easily absorbed, and easily crosses the blood-brain barrier, may be effective in the prevention and treatment of depression and dementia.1337 Look for a folate supplement that says “L-Methylfolate”, “5-methyltetrahydrofolate” or “5-MTHF” on the label. Even better, with the word Quatrefolic® or Metafolin® which are branded forms of folate ensuring their purity and effectiveness. Avoid any product, including multivitamins, which list “folic acid” on the label. Nootropics Expert® Recommendation Vitamin B9 (Folate) up to 500 mcg I recommend using Vitamin B9 (Folate) as a nootropic supplement. Your body does not make Vitamin B9 on its own. So you must get folate from food or a supplement. Vitamin B9 (Folate) is especially helpful for those suffering from anxiety, depression, panic attacks, or OCD. Folate can help improve energy levels, reduce insomnia, and help increase energy levels. Experience shows Vitamin B9 helps stop and reverse the symptoms associated with high homocysteine levels. Vitamin B9 is also particularly helpful to quell anxiety caused by social situations. Vitamin B9 can help you get a good night’s sleep. You may find it as effective as sleep meds and other nootropics used for sleep. You’ll awaken feeling refreshed and calm. Ready to start your day. The recommended dosage of Vitamin B9 (Folate) is up to 1,000 mcg per day. Start low at 500 mcg and see how your body reacts. Please refer to Dosage Notes in this chapter for adding the other B-Vitamins to your stack for an

optimal methylation cycle. Your neurotransmitters are counting on it.

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Vitamin B12 (Cobalamin) Vitamin B12 is known to enhance alertness, cognition, energy, vision, elevate mood, lower anxiety and pain, and relieve insomnia Vitamin B12 (Cobalamin) is one of 8 water-soluble B-vitamins that are absolutely vital to the highly optimized brain. And is essential to every cell in your body including your brain. Vitamin B12 is essential for the synthesis of DNA, RNA and neurotransmitters, the maintenance of myelin sheaths protecting neurons, and red blood cell formation. Deficiency in B12 results in myelopathy (spinal cord disease), neuropathy (nerve disease), sensory disturbances, imbalance when walking, weakness, and psychiatric problems ranging from cognitive and behavioral problems to dementia. Vitamin B12 as a nootropic can improve alertness, energy levels, boost attention span, concentration, intelligence and memory. B12 supplementation can help relieve stress, depression, insomnia and help balance your mood. Vitamin B12 has the coolest and most complex chemical structure of any nootropic we explore in Head First. Vitamin B12 is called “Cobalamin” because it contains the rare earth element cobalt.1338 Vitamin B12 is absorbed in your intestines from food or a supplement using a process called intrinsic factor. The vitamin is then transferred to transcobalamin II (TC-II/B12) which acts as a transporter. Through a very complex process which I’m not going to try to explain here, B12 is converted into the active forms coenzyme 5’-deoxyadenosyl and methylcobalamin (MeB12).1339 Foods rich in Vitamin B12 include fish, shellfish, meat (especially liver), poultry, eggs, milk and milk products.1340 The two best sources by far of B12 are clams and liver. You cannot get adequate amounts of Vitamin B12 from plants. Vegetarians and vegans are especially in danger of B12 deficiency. Regardless of what food and supplement manufacturers say. Plant foods contain analogs of B12 which are similar to, but not the same as, Vitamin B12. They bind to B12 receptors and block your intake of true B12. Trying to get your Vitamin B12 from yeast products like Red Star Nutritional Yeast or Marmite is also problematic. These products do not naturally contain B12 but are fortified with it. And Vitamin B12 is light sensitive. If stored in open bins or clear plastic bags or jars, B12 vaporizes and disappears. Meat and animal products are your best source of natural Vitamin B12. But once again, relying solely on

food for adequate B12 is difficult because it is destroyed during cooking.1341 You are much safer using a good Vitamin B12 supplement for your nootropic stack. See “Available Forms” later in this chapter for more. How does Vitamin B12 (Cobalamin) work in the Brain? Vitamin B12 (Cobalamin) boosts brain health and function in several ways. But two in particular stand out. 1. Vitamin B12 increases cognition. Vitamin B12 is a precursor in the biosynthesis of all major neurotransmitters in your brain including acetylcholine, dopamine, GABA, norepinephrine and serotonin. Vitamin B12 is an integral part of the one-carbon cycle involved in the synthesis of methionine. This amino acid, methionine donates the methyl group required for methylation to occur. This biochemical process helps synthesize neurotransmitters, myelin (the sheath that protects neurons) and keeps homocysteine levels in check. Elevated levels of homocysteine have been associated with several neurodegenerative diseases including Alzheimer’s and Parkinson’s Disease. Even mild Vitamin B12 deficiency has been associated with accelerated cognitive decline. Researchers at Tufts University examined data from 549 men and women enrolled in the Framingham Heart Study. They focused on scores on the Mini-Mental State Examination (MMSE), which is a short list of questions and tasks used to screen for dementia. The subjects were divided into 5 groups, based on their vitamin B12 blood levels. MMSE scores declined by 0.24 points per year over the 8-year follow-up period. Cognitive decline was faster in the bottom 2 groups that had the lowest levels of Vitamin B12. The researchers concluded that “having plasma (blood) Vitamin B12 levels from 187 to 256.8 pmol/L… predicts especially rapid cognitive decline”.1342 2. Vitamin B12 helps reduce depression. Vitamin B12 is a precursor in the biosynthesis of GABA and serotonin. GABA is an amino acid and neurotransmitter produced by glutamate in your brain. This inhibitory neurotransmitter prevents other ‘excitatory’ neurotransmitters from being released. Resulting in an anti-anxiety and calming effect. Serotonin is a neurotransmitter made from the amino acid tryptophan. This inhibitory neurotransmitter governs the stimulatory neurotransmitter dopamine from overwhelming your brain. Adequate serotonin levels make you feel confident, easy-going, flexible, happy, and positive. One case study out of India reviewed the case of a 57-year-old woman who was given months of antipsychotic and antidepressant medications. Including 2 rounds of electro-shock therapy before anyone thought to check her Vitamin B12 levels.

This woman’s symptoms included anxiety, constipation, movement abnormalities, perceptual disturbances (hearing her name called), lethargy, tearfulness and finally catatonia. She remained depressed, suicidal, and lethargic despite her treatment. Within 2 months of identifying her Vitamin B12 deficiency and subsequent treatment, this woman reverted to her baseline 14 years before. And remained stable with no additional treatment.1343 How things go bad Vitamin B12 deficiency usually causes neurological and psychiatric issues in adults aged 40 – 90. B12 deficiency rarely affects younger people. But can be a problem if the mother is deficient during pregnancy. A B12 deficiency can manifest as disease of the spinal cord (myelopathy), disease of the nerves (neuropathy), sensory disturbances, gait abnormalities, weakness, cognitive and behavioral disturbances, and dementia. ↓ Neuron myelin sheath is damaged ↓ Neurons degenerate ↓ Weakness, vision problems, cognition issues, abnormal reflexes ↓ Bladder and erectile dysfunction ↓ Tingling sensation, pain and numbness ↓ Delusions, hallucinations, memory decline, depression and dementia ↓ Brain shrinkage ↓ Impaired DNA synthesis and replication Vitamin B12 deficiency can often be caused by Pernicious anemia which is an autoimmune disease that affects the mucous membrane layer of the stomach. This can be a result of destruction of parietal cells, lack of hydrochloric acid, or a failure to produce intrinsic factor. Parietal cells are required to create intrinsic factor to supply your body with adequate Vitamin B12. When these cells are damaged, intrinsic factor is not produced. And B12 cannot be absorbed for use by your body and brain. Parietal cell death can be caused by excess alcohol consumption, ulcerative gastritis, H. pylori infection, gastric bypass surgery and even age. Intrinsic factor is required for Vitamin B12 absorption from food or supplements. If left untreated you experience B12 deficiency even if you’re getting B12 from food or supplements. If you or your doctor suspect Vitamin B12 deficiency and do a blood test, the labs may show B12 levels

within the bell curve. But it doesn’t reflect how much B12 is actually in your cells. Pernicious anemia is sometimes passed down through families. This is most common in those of Scandinavian or northern European descent. Grave’s Disease, and Addison’s Disease. Type-1 diabetes can also cause pernicious anemia. Review the symptoms of deficiency listed here. Do your research. And if you suspect you may be deficient in Vitamin B12, tell your doctor and take action now. If your doctor tells you that it’s not a problem, please find another doctor! Vitamin B12 (Cobalamin) benefits When you take Vitamin B12 (Cobalamin) as a nootropic supplement, it is transported across your intestinal wall by the carrier protein intrinsic factor. It is then degraded, freeing cobalamin to be attached to transcobalamin II for transport to cells in your body.1344 Vitamin B12 is a co-factor in the one-carbon cycle that is required for the synthesis of DNA, RNA, neurotransmitters (acetylcholine, dopamine, GABA, norepinephrine and serotonin), and the myelin sheath that protects each of the axons in your brain. This one-carbon pathway is involved in the synthesis of the amino acid methionine. This amino acid donates methyl groups for the methylation of DNA, RNA, neurotransmitters, and myelin. Methionine is synthesized from the amino acid homocysteine. Preventing high levels of this amino acid to accumulate will prevent problems throughout your body including neurodegenerative disease. Cobalamin is also required for the conversion of methylmelonyl CoA into succinyl Coenzyme-A for the myelin sheath that protects your axons. Problems with this conversion degrades myelin. Causing problems with your central nervous system and damaging axons needed for brain cell signaling. Vitamin B12 can: • • • • • • • • • • • •

Reduce the severity and frequency of asthma attacks and allergies Reverse early signs of Alzheimer’s Disease if caught in time Lift your mood by boosting the “happy molecule” serotonin in your brain Reduce the side effects of Metformin in diabetes patients Provide optimal concentration, focus and memory Reduce the risk of macular degeneration and prevent blindness Maintain healthy hair, skin, and nails Remove homocysteine and protect your heart Raise sperm counts and improve sperm mobility in men Prevent neuron damage if you lack intrinsic factor Reduce some of the symptoms of schizophrenia Help prevent osteoporosis and build strong bones

The key message here is to maintain optimal Vitamin B12 levels in your body and brain. Don’t be duped

by marketers selling Vitamin B12 energy drinks boasting more energy. Or a magic pill to boost memory, or aid in weight loss. If you have a specific health problem like pernicious anemia or are deficient in this vitamin, then B12 can help. If you maintain optimal levels of Vitamin B12 in your system, supplementing will not increase your energy levels. Vitamin B12 is a key brain vitamin that plays an important role in a healthy nervous system and optimally functioning brain. Low levels of B12 can definitely lead to poor memory and cognition. How does Vitamin B12 (Cobalamin) feel? Neurohackers who supplement with Vitamin B12 report a reduction in brain fog and better sleep. People on statins for cholesterol and metformin for diabetes report a dramatic decrease in pain. Neurohackers report better focus and mood, colors seem brighter and more intense, energy levels improve, and an overall improved sense of well-being. If you are Vitamin B12 deficient you may feel a big boost in energy. And feelings of deep exhaustion can disappear within a few days. The Research Much of the research in Vitamin B12 and B12 deficiency are presented as individual ‘case reports’ on one person. One report in French was about a woman with no history of psychiatric problems. But upon admission she was uncooperative, disoriented, had memory and attention problems, a sleep disorder and she looked older than her real age. This woman was depressed, had a guilt complex, devalued herself, and her movements and speech were very slow. A lab test revealed she had a problem with intrinsic factor. Her therapy was Vitamin B12 replacement using hydroxycobalamin 1,000 mg per day for 10 days. Her mental state improved dramatically within a few days.1345 Another case report was of a middle-aged man with Obsessive-Compulsive Disorder (OCD). He was given methylcobalamin therapy and symptoms of OCD dramatically improved.1346 Vitamin B12 and Folate Prevent Alzheimer’s A study in Stockholm explored the association of low Vitamin B12 and folate levels with the occurrence of Alzheimer’s Disease. A population-based study sampled 370 non-demented people aged 75 years or older and who had not been treated with B12 and folate. This group was followed for 3 years to detect the incidence of Alzheimer’s. The researchers compared

low levels of B12 and folate with people who had normal levels of the two vitamins. Subjects who had low levels of Vitamin B12 or folate had twice the risk of developing Alzheimer’s. And this association was even stronger in subjects with good baseline cognition. The study concluded that Vitamin B12 and folate may be involved in the development of Alzheimer’s Disease. And that monitoring blood B12 and folate concentration in the elderly may be relevant for the prevention of Alzheimer’s Disease.1347 Vitamin B12 (Cobalamin) to Treat Depression Research shows that people with major depression often have low blood levels of folate and Vitamin B12. Low folate levels are also linked to poor response to antidepressants. And treatment with folic acid and/or Vitamin B12 has been shown to improve response to antidepressants. Folate and Vitamin B12 are involved in one-carbon metabolism in which SAM-e is formed. SAM-e donates methyl groups that are crucial for neurological function. Increased homocysteine is a functional marker of both folate and Vitamin B12 deficiency. Increased homocysteine levels are found in depressed patients. One study out of Norway showed increased blood levels of homocysteine were associated with increased risk of depression (but not anxiety). The researchers concluded that doses of both Methylfolate (800 mcg daily) and Vitamin B12 (1 mg daily) should be tried to improve treatment outcomes for depression.1348 Dosage Notes Vitamin B12 is water-soluble and considered non-toxic in recommended doses. A varied diet including meat, seafood and milk products should provide enough Vitamin B12 to prevent deficiency. But vegetarians and vegans cannot get enough B12 from food and should supplement. Typical recommended dosage for nootropic benefit and optimal brain health is 100 mcg or 1 mg of Vitamin B12 per day. Neurohackers older than 40 and those who have a problem with Vitamin B12 absorption should use 100 – 400 mcg or 1-4 mg of B12 per day. If you test Vitamin B12 deficient, recommended dosage is 2,000 mcg daily for a week, then 1,000 mcg doses of B12 once per week for a month. Thereafter, your maintenance dose is 1,000 mcg monthly.1349 Side Effects Vitamin B12 (Cobalamin) is non-toxic. So is considered well-tolerated and safe. Doses as high as 2 mg of Vitamin B12 daily by mouth or 1 mg monthly by injection have been shown to produce no significant side effects.

When high doses of Vitamin B12 are given orally, only a small percentage can be absorbed which likely explains the low toxicity levels. Proton pump inhibitors and other drugs used to treat acid reflux is known to prevent absorption of Vitamin B12. So you may need to take B12 sublingually. Antibiotics, drugs to treat gout and metformin to treat diabetes all decrease Vitamin B12 levels or B12 absorption. If you use any of these drugs you should have your levels checked and possibly supplement with Vitamin B12. Nitrous oxide used as an anesthetic and recreational drug oxidizes and inactivates Vitamin B12. So you should likely get tested and possibly supplement with B12. Available Forms Vitamin B12 is available as tablets, capsules, liquid drops, sublingual tablets, sprays and lozenges. The sublingual tablets, sprays and lozenges are marketed as more absorbable or bioavailable. Some clinical studies do not support this claim, but user experience shows otherwise. Logic tells us that a lozenge or spray absorbed under your tongue gets into your bloodstream and across the blood-brain barrier more readily than something you swallow and need to digest. Low quality Vitamin B12 supplements, and B12 found in multivitamins or B-Complex formulas, is usually cyanocobalamin. This form of B12 is not well absorbed and produces a small amount of cyanide in your body (cyanocobalamin). Higher quality Vitamin B12 comes as methylcobalamin or adenosylcobalamin which are the forms of B12 naturally occurring in your body. Methylcobalamin is your better choice if you are deficient in B12 or have the MTHFR genetic defect which reduces your ability to methylate this vitamin. Adenosylcobalamin works better for some who want to avoid the cyanide that comes in cyanocobalamin, and who can’t tolerate methylcobalamin. Hydroxycobalamin is another high-quality form of Vitamin B12 that converts to methylcobalamin in your body. If you test Vitamin B12 deficient, your doctor may encourage you to get Vitamin B12 shots. Especially if you have pernicious anemia, nerve damage or chronic digestive problems like Crohn’s Disease or ulcerative colitis. But research has found that taking oral B12 supplements is as effective as B12 shots.1350 And user reviews support this finding.

Note that Vitamin B12 needs to be balanced with Vitamin B6 and Folate (Methylfolate) for best results if using as a nootropic supplement. Nootropics Expert® Recommendation Vitamin B12 (Cobalamin) 1 mg per day I recommend using Vitamin B12 as a nootropic supplement. Your body does not make Vitamin B12 on its own. So to get its benefits you must get it from food or take it as a supplement. I recommend staying away from cheap cyanocobalamin B12 supplements. Go with Methylcobalamin, Adenosylcobalamin, or Hydroxycobalamin. Vitamin B12 is especially helpful for those dealing with brain fog, fatigue, nerve pain, sleep and memory problems. Vitamin B12 supplementation is critical for anyone over 40 years old because of absorption issues with B12 from food. Vitamin B12 is also particularly helpful if you are using proton pump inhibitors for acid reflux, have Type-1 diabetes, or show positive for dementia or Alzheimer’s. The recommended dosage for Vitamin B12 deficiency is 2,000 mcg daily for a week, then 1,000 mcg doses of B12 once per week for a month. Then your maintenance dose is 1,000 mcg monthly. Remember that Vitamin B12 needs to be balanced with Vitamin B6 and Folate (Methylfolate) for best results if using as a nootropic supplement.

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Vitamin D Vitamin D has been shown to relieve depression & SAD, is critical for learning & memory, and helps prevent age-related cognitive decline Vitamin D3 (cholecalciferol or calciol) is the fat-soluble steroid hormone form of Vitamin D. The “sunshine vitamin” is considered essential. Your skin synthesizes Vitamin D3 from ultraviolet-B (UVB) sunlight. Nearly every tissue and cell type in your body and brain has Vitamin D receptors (VDR). It’s commonly associated with immune and bone health. But Vitamin D3 as a nootropic supplement is critical for optimal cognitive health. It’s an integral part of neurotransmitter synthesis, gene expression, DNA maintenance and repair, and the forms of neuroplasticity needed for memory formation and retrieval. Vitamin D deficiency (hypovitaminosis D) is an undeclared worldwide pandemic affecting nearly 50% of the population on this planet. The major cause of this Vitamin D deficiency is inadequate exposure to sunlight. Wearing sunscreen with a SPF of 30 reduces Vitamin D synthesis in your skin by more than 95%.1351 Working and living indoors in our modern world contributes to this problem. Those with a naturally dark skin tone require 3 – 5-times longer sun exposure to the make the same amount of Vitamin D as those with a lighter skin tone.1352 Also at risk of Vitamin D deficiency includes anyone who works indoors, breastfed infants, older adults, and anyone homebound, or who wear long garments for religious reasons. If you have fat malabsorption issues, obese, or on certain medications you are also at risk. You risk a host of problems if you don’t get enough Vitamin D. Including Type-2 diabetes, depression, cognitive impairment, Parkinson’s, or Alzheimer’s Disease among others. Vitamin D exists in two forms. Vitamin D2 is obtained from the UV irradiation of the yeast sterol ergosterol and is found naturally in sun-exposed mushrooms. UVB light from the sun strikes the skin, and humans synthesize Vitamin D3, which is the most “natural” form. Note: I’ll be using Vitamin D and Vitamin D3 interchangeably throughout this chapter. Supplementing with high quality Vitamin D3 is inexpensive and simple. If you could do one thing to improve the efficacy and potency of your nootropic stack. Add Vitamin D3 to your daily stack. Vitamin D3 is unique because it is not a standard vitamin. It’s actually a fat-soluble steroid hormone.

Vitamin D is mostly made in your skin from sun exposure. Not from food like most of our other vitamins. When Ultraviolet-B (UVB) light from the sun strikes your skin, your body synthesizes Vitamin D3. Vitamin D that comes from your skin, or from food or a supplement, is not active. It first requires hydroxylation in your liver by the enzyme vitamin D-25-hydroxylase (25-OHase) to 25(OH)D.1353 Then 25(OH)D requires further hydroxylation in your kidneys by 25(OH)D-1-OHase to form the biologically active form of vitamin D called 1,25(OH)2D (cholecalciferol). You get some Vitamin D from foods like fatty fish (tuna, salmon, and mackerel), beef liver, cheese, egg yolks, and mushrooms. Some foods in the USA are fortified with Vitamin D. It’s added to breakfast cereals, soy beverages, yogurt, and margarine. Check the nutrition fact panel on the food label. Cholecalciferol is also produced industrially for use in nootropic supplements, and to fortify foods. It is produced using ultraviolet irradiation of 7-dehydrocholesterol extracted from lanolin in sheep’s wool. Vitamin D3 directly or indirectly regulates the function of up to 2,000 genes in your body and brain.1354 Vitamin D works in concert with Vitamin D receptors (VDR) located throughout your body and brain. Vitamin D3 with Omega-3’s are needed for serotonin synthesis, release, and function. Regulating executive function, sensory gating, and social behavior.1355 And Vitamin D3 is involved in the synthesis of GABA, glutamate and glutamine, and dopamine in the brain.1356 Vitamin D3 protects against DNA damage through prevention of telomere shortening and inhibition of telomerase activity. And prevents oxidative damage to DNA.1357 Vitamin D3 is involved in neuromodulation, regulation of neurotrophic factors, neuroprotection, neuroplasticity, and brain development. All in areas of the brain associated with depression. Supplementation could be an important part of treatment of depression.1358 Recent research shows Vitamin D is involved in nerve growth factor (NGF) synthesis. Which is responsible for the growth and maintenance of neurons. Vitamin D is also involved in neuron apoptosis. Studies have shown that low Vitamin D levels interrupts this cell cycle. Leading to several neurological disorders including dementia, Parkinson’s, MLS, epilepsy, and schizophrenia.1359 Alzheimer’s disease is associated with a decrease in Vitamin D receptors in the hippocampus. Lack of gene expression from insufficient Vitamin D contributes to Parkinson’s Disease.1360 Hypovitaminosis D (low Vitamin D) is associated with an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. The increase in these specific cytokines is associated with the

degradation of the myelin sheath. Leading to Multiple Sclerosis (MLS). Studies are currently underway for using Vitamin D3 to reduce seizures in those dealing with epilepsy. The anticonvulsant effects are based on Vitamin D3’s ability to regulate the expression of genes. A process that is mediated by Vitamin D receptors.1361 Scientists and researchers in labs around the world continue to build on the knowledgebase for Vitamin D. And how the sunshine vitamin affects human cognition and overall health. How does Vitamin D work in the brain? Vitamin D boosts brain health and function in several ways. But two in particular stand out. 1. Vitamin D helps relieve depression. Vitamin D activates genes that regulate your immune system and the release of neurotransmitters including dopamine and serotonin. Research has also located Vitamin D receptors in areas of the brain linked to depression. A metaanalysis of clinical studies on depression and Vitamin D status including 31,424 participants showed that low Vitamin D concentrations is associated with depression.1362 One of several other studies on Vitamin D1363 and depression showed that older adults with low Vitamin D levels were 11-times more likely to be depressed than those with normal levels.1364 And if you’re currently using antidepressants without much success, this next study may provide some hope. A study conducted in Iran with 42 patients with major depressive disorder participated in a doubleblind, randomized, placebo-controlled trial. One group received 1,500 IU of Vitamin D3 plus 20 mg of fluoxetine (Prozac®), or fluoxetine alone for 8 weeks. In this 8-week trial, the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms.1365 2. Vitamin D is essential for learning and memory. Vitamin D has been shown to play a critical role in neuron cell growth and differentiation, neuron transmission, and the neuroplasticity that’s essential for optimal learning and memory.1366 Vitamin D has been shown in the lab to protect against age-related cognitive decline. In one study conducted in Detroit, researchers worked with aged rats. Older rats have problems with cognitive testing. Along with elevated levels of pro-inflammatory cytokines, decreased levels of antiinflammatory cytokines, and higher levels of amyloid-beta proteins in their brains. Supplementing with Vitamin D for only 21 days reversed the inflammation and improved the clearance of amyloid-beta. Showing potential for using Vitamin D to prevent age-related cognitive decline.1367 How things go bad Vitamin D deficiency is a global health problem. Over a billion people worldwide are Vitamin D

deficient.1368 The major cause of this deficiency is the lack of appreciation that getting enough sun every day is the major source of Vitamin D for most people. Very few foods contain Vitamin D. And foods that are fortified are inadequate to provide a child or adult’s daily requirement. Top that off with the media and mainstream medical establishment hysteria about skin cancer. And the use of sunblock. If you work indoors, wear ‘extensive’ clothing, use sunblock, are dark skinned, overweight, aged, or consciously avoid the sun, you are at risk for Vitamin D deficiency. ↓ Pathogens can inhibit Vitamin D receptors ↓ Lack of natural sun exposure depresses Vitamin D levels ↓ Caffeine inhibits Vitamin D receptors ↓ Testosterone levels decline ↑ Risk of bone fractures increases ↑ Increased risk of cancer, autoimmune disease, hypertension, infectious disease ↓ Severe Vitamin D deficiency can result in dementia and Alzheimer’s ↑ Increase in symptoms of depression Vitamin D3 supplementation can help alleviate depression and improve learning and memory. Vitamin D benefits Not too long ago, Vitamin D was simply known as the ‘bone vitamin’. But there has been a surge in Vitamin D research over the last decade. Out of that research, it was discovered that nearly every cell type and tissue in your body have receptors for this essential vitamin. And quickly changed how we understand the role of Vitamin D in the body. We now know that Vitamin D deficiency is a problem worldwide. To put this in perspective, studies estimate 64% of Americans don’t get enough Vitamin D.1369 We now have clinical evidence that Vitamin D influences our autoimmune system, heart health, prevents infectious disease, and supports optimal cognition. Vitamin D deficiency has been linked to Alzheimer’s and Parkinson’s disease, asthma, autism, depression, cancer, and diabetes. A Japanese study found that 1,200 IU of Vitamin D daily reduced the risk of getting the flu by almost

50%.1370 One 7-year study showed Vitamin D deficiency substantially increased the risk of non-Alzheimer’s dementia.1371 Another 7-year study associated higher Vitamin D levels with a significantly lower risk of developing Alzheimer’s.1372 Animal and human studies suggest that Vitamin D could help in the prevention and treatment of cognitive decline and dementia. How does Vitamin D feel? If you work or spend most of your time indoors, you’re getting less sun than you should. And you may notice that your mood deteriorates as you spend less time outside. This is especially noticeable in the winter if you live well far north or south of the Equator. A capsule of Vitamin D3 in the morning is like a little dose of sunshine. You’ll feel brighter even on the grayest of days. Many who supplement with Vitamin D3 report feeling happier. Energy levels are higher, and feelings of depression stay away. Some report a noticeable decrease in fibromyalgia pain. Pain after exercise is less pronounced. Seasonal depression is officially known as “Seasonal Affective Disorder” (SAD). Vitamin D3 is a potent remedy for many experiencing SAD. It’ll keep that winter depression at bay and reduce mood swings. Many report that supplementing with Vitamin D3 reduces insomnia. Sleep is deeper and your mood is better the next day. The Research Vitamin D may prevent autism A study led by Professor Brue Ames of Children’s Hospital Oakland Research Institute demonstrated that oxytocin, serotonin, and vasopressin are all activated by Vitamin D. Abnormal social behavior is one of the symptoms of autism. And has been previously linked to low serotonin and Vitamin D levels in the brain. This study shed light on the mechanism of action that could explain this relationship. The study showed that Vitamin D activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a Vitamin D response element (VDRE). And suppresses the transcription of TPH1 in tissues outside the blood-brain barrier. The study explains that this mechanism shows how low Vitamin D hormone levels result in aberrant serotonin synthesis. Leading to abnormal brain development. The study authors suggested, “Supplementation with Vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.”1373

Vitamin D may prevent dementia & stroke Dementia is one of the greatest health challenges of our time. An estimated 44 million people worldwide suffer from dementia. This number is expected to triple by 2050 as the population ages. A recent study at the University of Exeter Medical School found that adults who were slightly deficient in Vitamin D have a 53% increased risk of developing dementia of any kind. That risk increased to 125% in those who were severely deficient in Vitamin D. The same study found that the moderately deficient group were 69% more likely to develop Alzheimer’s. And the severely deficient were 122% more likely to develop this disease.1374 Another study at the University of Heidelberg in Germany included 3,316 patients who were referred for evaluation of their arteries. Those with low Vitamin D levels were found to be more likely to have a fatal stroke within the next 7 years. The researchers concluded, “vitamin D supplementation is a promising approach in the prevention of strokes”.1375 Vitamin D prevents depression Seasonal Affective Disorder (SAD) is a mood disorder characterized by depression that occurs during fall and winter months when sunlight levels are low. SAD typically coincides with a sudden drop in Vitamin D levels in the body. Several studies have suggested that SAD could be due to changing Vitamin D3 levels. Which affects serotonin levels in the brain.1376 One study with adults dealing with Vitamin D deficiency found that supplementing with 4,000 IU of Vitamin D daily for 2 months relieved their depression symptoms.1377 Another study recruited 441 people in an outpatient clinic in Norway. This randomized, double-blind trial had patients using 20,000 or 40,000 IU Vitamin D per week or placebo for 1 year. Subjects with serum Vitamin D levels below 40 nmol L were significantly more depressed than those with levels above 40 nmol L. In the two groups given Vitamin D there was a significant improvement in depression symptoms after 1 year. But no improvement in the placebo group. The study concluded, “It appears to be a relation between serum levels of 25(OH)D and symptoms of depression. Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship.”1378 Vitamin D Recommended Dosage The Institute of Medicine recommends 4,000 IU per day for Vitamin D3. Vitamin D is fat-soluble. So make sure you take it with a meal containing healthy fats. Or a tablespoon of unrefined coconut oil or extra-virgin olive oil. A study published in the American Journal of Clinical Nutrition suggests optimal Vitamin D status is

achieved with a serum (blood) 25-hydroxyvitamin D concentration >75 nmol/L. To achieve blood levels of 100 nmol/L, research has found that you need total daily Vitamin D supplementation of 4,000 IU. It is possible to get your daily dose of Vitamin D from the sun. And total-body sun exposure provides the equivalent of 10,000 UI of Vitamin D.1379 But chances are none of us has the opportunity to sunbathe nude every single day to get our dose of Vitamin D. To determine how much Vitamin D3 you needed to take to achieve optimal concentrations of this crucial vitamin, researchers recruited 138 volunteers for a 6-month randomized, double-blind, placebocontrolled trial. The researchers found that if your blood Vitamin D status was less than 55 nmol/L you needed a daily intake of 5,000 IU. And for those above the 55 nmol/L you needed a dose of 3,800 IU of Vitamin D3 per day.1380 The Institute of Medicine also found that the dose for lowest observed adverse effect level is 40,000 IU of Vitamin D daily for at least 12 weeks. Get your Vitamin D levels checked. Be sure the lab tests for “25-hydroxyvitamin D”. To raise your blood levels of Vitamin D to optimal levels, you need to take 100 IU of Vitamin D3 for each 1 ng/mL you need to raise it.1381 Vitamin D side effects Vitamin D is non-toxic. So is considered well-tolerated and safe. Side effects are rare but can include dry mouth, fatigue, headaches, metallic taste, nausea, sleepiness, and vomiting. Doses of Vitamin D higher than 4,000 IU daily is possibly unsafe because it could cause excessive blood levels of calcium. But note that much higher doses are sometimes used for short-term treatment of Vitamin D deficiency. Vitamin D could worsen atherosclerosis (hardening of the arteries). If you have sarcoidosis, histoplasmosis, are hyperthyroid, have lymphoma, or tuberculosis Vitamin D could increase blood calcium levels causing kidney stones and other problems. Vitamin D may affect blood pressure. So be cautious about using Vitamin D if you’re dealing with blood pressure disorders, are taking drugs or supplements that affect blood pressure. Vitamin D may affect blood sugar levels. So if you’re taking drugs for diabetes or insulin you should monitor your Vitamin D levels and adjust medication as necessary. Some drugs used to treat lower cholesterol, psoriasis, calcium channel blockers, corticosteroids, and

others may interact with Vitamin D. Type of Vitamin D to buy The preferred way of getting Vitamin D is by exposing your skin to the sun. But the color of your skin will affect the synthesis of this essential vitamin. Lighter skin may require 45 minutes of exposure 3-times per week. Dark skin may require up to 3-hours of exposure 3-times per week. But since most of us spend so much time indoors. And have the nasty habit of using sunscreen when we do go outside. To maintain adequate Vitamin D levels supplementation is best. Vitamin D3 (cholecalciferol) is preferred over Vitamin D2 (ergocalciferol), since D3 is the type of Vitamin D your body synthesizes naturally. A meta-analysis by the Cochrane Database investigated mortality rates for those who supplemented with Vitamin D2 vs Vitamin D3. The analysis of 50 randomized controlled trials included 95,000 participants showed: • •

A 6% risk reduction among those who used Vitamin D3 A 2% risk increase among those who used Vitamin D2

The overwhelming evidence shows that you are more likely to die using Vitamin D2 rather than D3.1382 So if your doctor prescribes synthetic Vitamin D2 (Drisdol), kindly decline and get a Vitamin D3 supplement at the vitamin shop. Vitamin D3 is available in softgel capsules, tablets and as a liquid. If you have trouble digesting fat, Vitamin D injections are also available by prescription. Calcitriol is a synthetic Vitamin D analog available by prescription which is used by dialysis and hypoparathyroid patients. Nootropics Expert® Recommendation Vitamin D3 4,000 IU’s per day I recommend using Vitamin D3 as a nootropic supplement. Your body does make Vitamin D on its own by synthesizing it from UVB sunlight on exposed skin. Which is the preferred way of getting Vitamin D. But all kinds of things can interfere with getting enough Vitamin D from sunlight. Fall and Winter in both hemispheres, cloud cover, smog, skin color, sunscreen, and too much clothing are all factors. And most of us spend so much time indoors, to get its benefits you should take Vitamin D3 as a supplement.

It’s best if you get your Vitamin D levels checked. Be sure the lab tests for “25-hydroxyvitamin D”. To raise your blood levels of Vitamin D to optimal levels, you need to take 100 IU of Vitamin D3 for each 1 ng/mL you need to raise it. Vitamin D is especially helpful for anxiety and depression. Vitamin D deficiency has been associated with depression, schizophrenia, psychotic symptoms, and suicide.1383 Vitamin D is also helpful for those dealing with autism, Alzheimer’s, and Parkinson’s. Doses should not exceed 10,000 IU daily unless supervised by a doctor. Vitamin D toxicity can happen with doses exceeding 40,000 IU per day for an extended period. Vitamin D supplementation is one of the simplest and least expensive ways to optimize your brain. And should be part of every nootropic stack. Vitamin D is fat-soluble. So make sure you take your dose with a meal. Or a high-quality fat like unrefined coconut or extra virgin olive oil. But please see the “Vitamin D Side Effects” section of this chapter above for conditions and medication interactions before you start using Vitamin D.

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Zinc Zinc improves alertness, cognition, focus, memory, learning, recall, reduces brain fog, is an antioxidant, helps neuroplasticity, and protects against glutamate-toxicity. Zinc is an essential trace element required for optimal brain health and cognition. Zinc is integral to the synthesis of proteins, the regulation of signaling cascades, gene transcription and neurotransmitter transport. It’s involved in DNA repair and synthesis and methylation. You may think of zinc as a natural cold remedy or the white lip balm you use at the beach. But zinc is needed in small amounts every day to maintain optimal brain function and overall health. In practical terms, adequate levels of zinc in your system works as an antioxidant fighting free radical damage. It helps maintain both male and female hormone balance. And zinc plays a role in neurotransmitter release affecting learning, memory, and mood.1384 When zinc levels are low, you’ll feel fatigued, concentration will be poor, you’ll get sick more often, and simple wounds won’t heal. Zinc inhibits NMDA receptors which reduces glutamate toxicity. And zinc modulates the activity of proteins such as receptors and enzymes that are involved in the regulation of macromolecules, the regulation of signaling cascades and gene transcription, and transport processes. Low zinc levels are found in those suffering from depression, and the lower the level the more severe the depression. Zinc increases serotonin uptake in select brain regions which boosts the efficacy of antidepressants. And it reduces depression because is increases BDNF. Zinc is involved in preserving genomic stability by regulating redox homeostasis (both oxidant and antioxidant signaling), DNA repair, synthesis, and methylation. Zinc inhibits the production of inflammatory cytokines (including nuclear factor-κB). And zinc protects against cognitive decline due to toxic copper levels.1385 Adequate levels of zinc are crucial for growth and development when you’re young. And required for proper taste and smell. Our earliest physical evidence of zinc for therapeutic use comes from the wreck of the ancient ship “Relitto del Pozzino” which sank off the coast of Tuscany around 120 B.C. Archaeologists found the remains of a 2,000-year-old medicine chest containing several tin pyxis (cylindrical box with a lid). Inside one of the tins were five medicinal tablets about the size of an American quarter and perfectly preserved. The pills contained a zinc compound which ancient writings tell us may have been used as an eyewash.1386 Zinc deficiency is common around the world including in the USA. This deficiency occurs because we don’t eat enough foods that contain zinc.1387 Your body needs about 10 – 20 mg of zinc per day because

it can’t store zinc. You get zinc from eating seafood like oysters or lobster. Beef, pork, and chicken provide smaller amounts of zinc per serving. And it’s also present in eggs, yogurt, cheese, and some nuts. But not only don’t most of us eat enough zinc-containing food, many plants contain phytates which block the absorption of zinc in your body. So vegetarians are particularly vulnerable to zinc deficiency. We’ll dive deeper into zinc deficiency and its causes below in the section “How things go bad”. And we’ll cover the easily recognizable symptoms of deficiency as well. How does Zinc work in the brain? Zinc boosts brain health and function in several ways. But two in particular stand out. 1. Zinc is an antidepressant. Zinc plays a role in modulating your brain and body’s response to stress and depression. More than 100 enzymes in your body use zinc help make DNA, protein synthesis, and cell division. Zinc is also critical for signaling between and within neurons and other cells in your body. Zinc fingers are present in at least 3% of all your cells. Proteins that contain zinc fingers act as interaction modules that bind DNA, RNA, proteins, and other molecules.1388 The highest amount of zinc is found in your brain. Particularly your hippocampus. Zinc deficiency can lead to symptoms of depression, aggression, seizures, violence, ADHD, and problems with learning and memory. A study published in the American Journal of Psychiatry shows that malnourished children exhibit a striking increase in behavioral disorders and aggressive behavior. Kids with nutritional deficiencies demonstrated a 41% increase in aggression by age 8! And at age 17, they demonstrated a 51% increase in violent and antisocial behavior. The malnourished kids weren’t getting enough critical minerals like zinc and iron. Or the B vitamins they needed to develop healthy nervous systems.1389 Levels of zinc have been found to be low in those suffering from depression. In fact, the more depressed someone is, the lower the zinc level.1390 Several human studies have demonstrated that supplementing zinc when using SSRIs help in the effectiveness of these antidepressants. One double-blind, randomized trial with 44 patients with major depression were randomly assigned to receive zinc or a placebo. At the conclusion of the 12-week study, the researchers found that “zinc supplementation together with SSRI antidepressant drugs improves major depressive disorders more effectively than in patients who were using a placebo plus antidepressants (SSRIs).”1391 2. Zinc is required for memory formation. Research in the last decade has shown that the presence of zinc in synaptic vesicles of excitatory neurons in the cerebral cortex and hippocampus

and regulates synaptic plasticity. Long-term potentiation is a form of synaptic plasticity that has been shown to underlie learning and memory. Zinc in these vesicles is critical to proper function of these brain circuits.1392 Zinc deficiency is associated with poor memory. And deficiency impairs signaling of brain-derived neurotrophic factor (BDNF) which is also involved in long-term potentiation and memory.1393 One very recent study revealed that the presence of zinc changes the dynamic of release of neurotransmitters like dopamine. Zinc causes the cellular pore to close more slowly than usual. Meaning the vesicle stays open longer. And releases more of neurotransmitter molecules. The researchers concluded, “Our results finally provide a connection between zinc and the regulation of neurotransmitter release. This could be important for the formation and storage of memories.”1394 Read the reviews of neurohackers supplementing with zinc and many report better energy and focus. Clinical research backs this up. But nearly always when correcting a zinc deficiency.1395 One Italian study investigated whether zinc supplementation could help restore memory in stroke patients. 26 patients took 10 mg of zinc daily for 30 days. On day 30 of the trial, researchers found that zinc supplementation significantly assisted in neurological recovery in the stroke patients.1396 And animal models suggest that zinc supplementation may increase resilience to Traumatic Brain Injury (TBI). For treating anxiety, depression, learning, and memory deficits caused by TBI. In this trial, rats with injury to the frontal cortex were fed either a zinc supplement or zinc supplemented diet. The rats were also given a zinc injection an hour after injury. The research team found that zinc supplementation may be an effective treatment option for improving cognitive impairment and depression following TBI.1397 How things go bad Zinc deficiency is a problem world-wide including in countries like the United States for several reasons. Our modern diet typically includes a lot of grains which are usually processed including packaged grain products like cereals. Zinc is found in grains. But this type of zinc is bound to phytates naturally found in these grains. Which block zinc absorption in your body. So zinc found in whole foods like grain and legumes are not a good source of this essential trace element. And the zinc you get from eating meat can also be blocked if your meal contains grains or legumes. Eating high carbohydrate foods, especially processed foods in the USA and other western countries are

one of the reasons zinc deficiency is increasing. If you’re vegan or vegetarian, you’re particularly susceptible to zinc deficiency. If you have chronic digestive problems, leaky gut syndrome, or drink too much alcohol you’re in danger of zinc deficiency. Zinc deficiency symptoms include: • • • • • • • • • • • • • • • • • •

Cravings for salty or sweet foods Eating disorders like bulimia or anorexia Chronic fatigue syndrome Hair loss Irritable bowel syndrome Impaired growth and sexual development (in kids) Infertility & impotence - hypogonadism in males Iron non-responsive anemia Hormonal issues like bad PMS symptoms Hyperactivity (as in ADHD) Delayed wound healing Impaired adrenal function resulting in anxiety and stress Low immunity (you get colds and flu often) Pica (eating dirt) Poor concentration and memory Skin disorders like acne Taste and smell problems Weight loss or gain

Any of these problems can happen at any age including in the developing child. And can be a result of not getting an adequate supply of zinc. Zinc benefits Zinc plays a critical role in how well your brain and body function. Adequate levels of zinc will increase your immunity and help you fight colds. A Cochrane review concluded that “zinc (lozenges or syrup) is beneficial in reducing the duration and severity of the common cold in healthy people, when taken within 24 hours of onset of symptoms”.1398 Zinc is a potent antioxidant and anti-inflammatory which helps support healthy cell division and a healthy brain. Zinc balances hormones which have a direct role in not only your sexual health. But in controlling anxiety, stress, mood, and sleep. Healthy zinc levels help lower inflammation and oxidative stress. The endothelium or thin layer of cells that line blood vessels rely on adequate zinc levels. Supporting a strong blood-brain barrier and cerebral blood flow.

Zinc is involved in protein synthesis which is required by your body to use the amino acids you get from food. Which are needed for neurotransmitter synthesis and contributing to energy production within mitochondria in every one of your brain cells. Healthy energy levels and avoidance of chronic fatigue rely on adequate zinc levels. Low zinc levels are a biomarker for depression. And under conditions of chronic stress, you tend to get rid of zinc through sweat, urine, and your saliva. So if your depressed you may want to try supplementing with zinc. Especially if you’re on SSRIs or other antidepressants. Research has found antidepressants and anti-anxiety meds work better when stacked with a zinc supplement. How does Zinc feel? Most neurohackers report that supplementing with zinc helps them relax before bed and sleep better. Recovery from workouts is faster. Many report that zinc helps boosts their libido. Zinc first thing in the morning seems to help many with energy and focus throughout the day. Zinc supports a healthy immune system so you can avoid colds and the flu. And if you come down with a bug, zinc can shorten the duration of the illness. Some neurohackers say zinc keeps allergies from flaring up. And many with skin problems say zinc supplementation reduces acne because it’s anti-inflammatory and antibacterial. If you are Adult ADHD, you may experience a decrease in anxiety or perception of stress. And notice an improvement in mood. One thing to note from all the research is improvements from using zinc only manifest if you are zinc deficient. With our modern diet, chances are you are zinc deficient. See “Zinc recommended dosage” below. Zinc Clinical Research Zinc’s role in anxiety & depression The latest research suggests depression is associated with decreased neurogenesis and enhanced neurodegeneration. Which in part is the result of inflammation. And lately there is mounting evidence that depression could be related to decreased zinc levels.1399 Zinc deficiency leads to less zinc in neuron synapses which results in an increase in NMDA receptors. This can cause an overload of toxic glutamate. With an overabundance of glutamate we get a decrease in GABA, BDNF, and nerve growth factor. This excitotoxicity is thought to be responsible for seizures, migraines, dementia, anxiety, depression, and bipolar disorder.

A double-blind, placebo-controlled trial in Japan worked with 30 women to study the effect of zinc supplementation on mood. Half of the women took a multivitamin. And the other half received a multivitamin with 7 mg of zinc per day for 10 weeks. The women who took the multivitamin/zinc combo showed a significant reduction in anger, hostility, and depression. The women who took only the multivitamin showed no improvement in mood.1400 Another study with depressed overweight subjects found that depression decreased in those supplementing with zinc. But zinc produced no effect on mood in those who were not depressed in the first place. Researchers concluded that the improved mood in overweight subjects was likely through increasing BDNF levels by using zinc.1401 Zinc may relieve symptoms of ADHD In the last decade, several studies have been conducted into the role trace elements like zinc play in ADHD. Zinc is required for the production and modulation of melatonin which helps regulate dopamine function.1402 So the theory is that those with ADHD may benefit from supplementing with zinc. A double-blind, placebo-controlled trial in Turkey was conducted with 400 boys and girls with a primary diagnosis of ADHD. Half the group received 150 mg zinc sulfate for 12 weeks while the control group got a placebo. The study concluded “Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD.”1403 Another study found that free fatty acids and zinc levels were lower in those with ADHD. But concluded that they didn’t know if zinc deficiency was the principal cause of ADHD. Or a secondary cause. A study in Croatia again showed that supplementing with 55 mg per day of zinc sulfate helped reduce the symptoms of ADHD.1404 Considering the major role zinc plays in everything from cell growth to DNA synthesis to neurotransmitter synthesis and transport. And if your child is diagnosed ADHD and you don’t want to start them on stimulants. You may want to try zinc with a good Omega-3 high in DHA and see if you witness any improvement in ADHD symptoms. Zinc may prevent autism Autism spectrum disorders (ASD) range from a severe form called autistic disorder, to a milder form called Asperger syndrome. If a child has specific symptoms of either of these disorders, but does not meet specific criteria for either, the diagnosis is called pervasive developmental disorder not otherwise specified (PDD-NOS).

This complex disease can be inherited, but likely also involves environmental factors.1405 A study published in Biomarker Insights in 2011 worked with 79 autistic subjects to study the association between copper and zinc plasma levels and individuals with autism, Asperger’s, and PDDNOS. Participants in the study were tested for zinc, copper, and antioxidant levels. Then based on their deficiencies, they were prescribed the appropriate dose of antioxidants (Vitamin C, E, B6 as well as Magnesium, and Manganese if warranted). And they were given zinc picolinate daily for at least 8 weeks. At the conclusion of the therapy, those with autism and PDD-NOS had significantly lower levels of copper. All three groups had higher levels of zinc. Severity of symptoms decreased in autistic individuals following zinc and Vitamin B6 therapy related to awareness, receptive language, focus and attention, hyperactivity, tip toeing, eye contact, sound sensitivity, tactile sensitivity, and seizures. But none of the symptoms in the Asperger’s patients improved after therapy.1406 Zinc recommended dosage The recommended adult dosage is 30 mg of zinc daily, balanced with 2 mg of copper. The best food source for zinc by far is oysters. Trailing far behind is other seafood, beef, pork, chicken, some nuts, and some dairy products. Vegans and vegetarians take note: don’t count on getting any benefit from zinc supplied by vegetables because the phytates in veggies block zinc absorption in your body. Your body needs zinc, but too much zinc is toxic. And it’s difficult to test for zinc using lab tests. But there is a simple DIY test first reported in The Lancet that can help you determine zinc levels. Premier Research Labs sells a Liquid Zinc Assay that is available from most local and online vitamin shops. You taste a teaspoon of Zinc Assay and depending on how the liquid tastes, you can assess your levels according to their guide. Clearly there is a sweet spot for zinc consumption, and more is definitely not better. More than 50 mg zinc per day can reduce copper levels, mess with iron function, and reduce immune function. Zinc Side Effects Zinc toxicity typically happens when you take too much zinc. And can result in abdominal cramps, diarrhea, headaches, loss of appetite and vomiting. Antibiotics like Cipro® and tetracycline interact with zinc. Inhibiting the absorption of both zinc and the antibiotic.

Zinc can reduce the absorption of the rheumatoid arthritis drug penicillamine. To prevent this interaction you should take your zinc supplement at least 2 hours before or after you take your arthritis meds. Some diuretics can increase urinary excretion of zinc by as much as 60%. Prolonged use of these drugs can severely deplete your zinc levels. Zinc can raise your blood pressure. And too much zinc for men can be suppress testosterone and over inhibit DHT. Resulting in symptoms often associated with using the hair growth drug finasteride. Men should also note that too much zinc can dull nerves including nerves in your penis. Because excess zinc can over-inhibit NMDA receptors. Type of Zinc to buy Zinc is sold in as zinc gluconate, zinc sulfate, zinc ascorbate, zinc picolinate and various other forms. The percentage of bioavailability for zinc varies by form: • • • • • • •

Zinc Ascorbate 15% Zinc Bisglycinate 25% Zinc Carbonate 52% Zinc Citrate 31% Zinc Chloride 48% Zinc Sulphate 22% Zinc Picolinate 20%

So if you’re using Zinc Picolinate 50 mg tablet, your body may only get about 20% of that zinc for use by your cells. But more importantly is the fine balance between copper and zinc. Zinc reduces the amount of copper your body absorbs because copper competes with zinc to bind with metallothionein (binding protein that brings zinc into the cells). The ratio of copper and zinc in your body is more important than the amount of each. Nootropics Expert® Recommendation Zinc 30 mg per day I recommend using Zinc as a nootropic supplement. Your body does not make Zinc on its own. So to get its benefit it needs to come from your diet. Or you must take it as a supplement. Zinc is especially helpful for treating anxiety and depression. Studies have demonstrated that zinc levels are low in those dealing with depression. And the lower the zinc level, the more severe the depression. Studies have also shown that if you are having limited success using prescription anti-anxiety drugs or antidepressants that you may increase their effectiveness by supplementing with zinc.

Zinc is also particularly useful in helping alleviate the hyperactivity part of ADHD. Impaired impulsivity and improved socialization get a boost as well. Zinc is also required for efficiently encoding and retrieving memories. Zinc deficiency is a problem worldwide. Especially if you’re vegan or vegetarian. But too much zinc is toxic. Keep your dose of zinc below 50 mg per day. And stack it with 2 mg of copper to keep your copper/zinc ratio stable.

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NOOTROPIC STACK RECOMMENDATIONS In this book we have looked at over a hundred nootropic supplements. Here we’re going to take it a step further and look at some recommendations. Most neurohackers find that to reach their brain hacking goals, it takes a combination of supplements working together. We call this a “nootropic stack”. And all it means is 2 or more supplements working together, in synergy, to fix something in the brain. Or boost something. When it comes to boosting cognitive performance – you can choose to improve memory, focus, stamina, neuroprotection, creativity, and mood. And I realize this sounds like an overall, general type of neurohacking. But I’ve found that “fixing” or repairing a problem with your brain falls under the category of “boosting cognitive performance”. Everything else tends to fall into place. But one of the first things I want you to understand is “one-size-fits-all” doesn’t apply when it comes to nootropic supplements. There isn’t one “magic pill” no matter what the television commercials say. Each of us has a brain that is unique to us. Our brain ‘wiring’ is influenced by genetics, food, water, environmental toxins, lifestyle, and a thousand other things. This uniqueness was verified by researchers at Carnegie Mellon University who used a diffusion MRI to map the brain’s structural connections in 699 brains. They found that each person’s connections are so unique they could identify a person based on this brain “fingerprint” with near perfect accuracy.1407 So when recommending certain nootropics to help brain function, please understand that these are just ‘suggestions’. This is certainly not medical advice. And caution is strongly advised when using any of these supplements. If possible, work with a naturopathic health professional who understands natural supplements. How they interact with certain health conditions. And many prescription drugs. Always start with the lowest dose possible to see how your body reacts. Understand that combining two or more nootropics could mean reducing the dosage of each. Successfully using nootropic supplements to boost, and repair your brain means a lot of trial and error to find out which nootropics in this book are appropriate for you. For each of these recommendations, I encourage you to refer to the previous chapter which covers each nootropic in much more detail. And includes dosage notes, side effects, drug interactions, and available forms.

Best Nootropics for Cognition, Thinking and Decision-Making Ever gone to the supermarket to get a box of Cheerios? And it wasn’t until you got to the supermarket, you realized that there were 20 difference kinds of Cheerios. You saw original Cheerios. There were honey-nut Cheerios, apple-cinnamon, multigrain, banana nut, and then of course all the generic varieties of Cheerios. And then you find yourself spending a half hour in the cereal aisle of the supermarket. Trying to choose between boxes of Cheerios. Do you think this could be a problem? Cognition is the mental action or process you go through when hunting down the ideal box of Cheerios. And understanding it through thought, experience, and your physical senses. Cognition includes thinking, knowing based on experience, short-, working-, and long-term memory, decision-making and problem solving. Whoever thought selecting a box of Cheerios could be so complicated? There’s a lot going on in your brain making the ideal selection and will likely take more than one nootropic. You can start with: •

Alpha GPC 300 mg 3-times per day or CDP-Choline 300 mg twice per day. Both nootropics help boost acetylcholine (ACh) in your brain. ACh is associated with learning and memory, concentration and focus.

•

Lion’s Mane Mushroom 1,000 mg twice per day. Lion’s Mane increases Brain Nerve Growth Factor or neurogenesis. Improving attention, focus, encoding new memories, thinking, depression, anxiety, and helps repair damaged neurons.

•

L-Tyrosine 500 mg twice per day. L-Tyrosine is a precursor to dopamine in your brain. More dopamine helps improve alertness, focus, working memory and executive function (decisionmaking).

•

Rhodiola Rosea 150 - 200 mg per day. Rhodiola Rosea boosts mood by influencing serotonin and norepinephrine levels in your brain. Rhodiola is known for improving alertness, energy, memory, mood, is anti-anxiety and anti-depressant, reduces fatigue, and boosts cognition and concentration.

•

Vitamin B6 up to 100 mg per day. Vitamin B6 is a required coenzyme for the synthesis of most major neurotransmitters in your brain. And helps enhance alertness, cognition, energy, memory and mood. Your brain cannot make these critical neurotransmitters without Vitamin B6.

•

Vitamin B9 (folate) 400 mcg per day. Folate is required for the synthesis of nearly all major neurotransmitters in your brain. Folate is known to improve mood, energy, initiative, alertness, concentration, psychomotor speed, and social activity

•

Vitamin B12 100 mcg per day. Vitamin B12 is essential for the synthesis of DNA, RNA and

neurotransmitters in your brain. B12 enhances alertness, cognition, memory, decision-making and mood. Your brain cannot make these critical neurotransmitters without Vitamin B12. You’ll find me recommending B-Vitamins often in these stacks. Because without the B-Vitamins, you’re brain simply won’t work. Many neurohackers, myself included, found it wasn’t until we added critical B-Vitamins to our nootropic stack that took our cognition to the next level. For each nootropic in this stack, please refer to the previous section of this book where each supplement is listed. There you’ll find dosage recommendations, side effects, drug contraindications and more.

Best Nootropics for Memory Let’s go back to the cereal aisle in the supermarket for a minute. Your search for the perfect box of Cheerios relies on your memory. The type of Cheerios you bought before. Warnings from the Environmental Working Group about GMO’s. Your kid’s favorite Cheerios. How to read the labels. Remembering the shopping list before you left home. There’s a lot going on in your brain just to buy a box of Cheerios. And it uses several different types of memory. Short-term memory is also known as primary or active memory. And is limited to what you remember for 20 to 30 seconds. At this point we’re comparing the different kinds of Cheerios sitting on the supermarket shelf. Long-term memory is the type of memory associated with an event or information you acquired long ago. This is a complicated form of memory influenced by your perception of an event or thing, conditioning, or any other input. And is encoded using long-term potentiation and strengthening neurons and synapses. Long-term memory comes in when you remember that your family hated the type of Cheerios you brought home 3 weeks ago. And made you vow to never buy them again. Working memory is distinct from short-, and long-term memory. These are memories that are not only remembered, but simultaneously processed with information that is important to you. You remember the purpose of the information, and why you decided to remember it. Working memory comes in when your reading Cheerios box labels. And recall that you should avoid GMO’s. And why GMO’s are bad for you. Added sugar is bad for you too. Each type of memory can be assisted by different nootropics. Because neurotransmitters, cerebral blood flow, long-term potentiation, hormones and more all come into play for memory. Just to buy a box of Cheerios. •

Alpha GPC 300 mg 3-times per day or CDP-Choline 300 mg twice per day. Both nootropics help boost acetylcholine (ACh) in your brain. ACh is associated with memory and learning, focus and concentration.

•

DHA (Omega 3) 1,000 mg per day. DHA makes up a large portion of your brain’s gray matter.

This fatty acid helps form cell membranes, neurons, and synapses which are needed to form and encode memories. •

Huperzine-A 200 mcg every 2nd day. Hup-A helps promote memory by optimizing acetylcholine (ACh) levels. Optimizing ACh with Huperzine-A means you need to make sure there’s enough material available to make ACh in your brain. And we do that by using Alpha CPC or CDPCholine.

•

L-Theanine 100 mg 3-times per day. Found naturally in green tea and available as a nootropic supplement, L-Theanine helps optimize GABA, dopamine and serotonin. Improving anxiety, focus, learning, and mood. This prevents you from melting down in the cereal aisle in the hunt for the perfect Cheerios selection. Great for taming anxiety and for sleep.

•

Noopept 10 mg 3-times per day. Noopept stimulates dopamine, and nicotinic acetylcholine (ACh) and serotonin receptors in your brain. Boosting cognition, memory, retention, logical thinking, improving your reflexes and mood. Here we’re taking our Cheerios hunt to the next level.

•

Phosphatidylserine (PS) 100 mg 3-times per day. PS is vital for brain health. Highly concentrated in cell membranes, PS helps in the release, storage and activity of neurotransmitters and receptors. Boosting cognition, focus, memory and recall.

Boosting all types of memory with this nootropic stack means you remembered to grab the grocery list before you left home. You realize your family likes only one type of Cheerios. You recall where it is on the shelf once you get to the supermarket. And within a couple of weeks, your 30 -minute Cheerios hunt has been whittled down to 30-seconds. Life is good. Just a reminder to check dosage recommendations, side effects, drug interactions and more in the chapter before this where each nootropic supplement is discussed in much more detail.

Best Nootropics for Depression & Anxiety Do you remember what it used to be like to be in a ‘good mood’ all of the time? Making the trip to the supermarket to pick up the family’s Cheerios was fun. Simply marveling at the marketing ingenuity behind 20 different kinds of Cheerios made you laugh. There was no anxiety behind choosing the right box of Cheerios. And no depression behind the ridiculous increase in Cheerios prices from two years ago. But anxiety and depression are something most of us have had to deal with at one time of another. For me, being ADD and hypothyroid was like a double whammy. And it took a while to dig out of the hole I was in. Anxiety and depression are often ‘grouped’ together both in nootropic circles as well as in the psychiatric/medical world. But they are two distinctly different conditions. Even though the cause of anxiety and depression may overlap. All kinds of conditions can contribute to anxiety and depression. Neurotransmitter levels that are

deficient or out of balance can cause severe depression. Illness and stress can cause anxiety and depression. Poor cerebral blood flow, a lack of Brain-Derived Neurotrophic Factor (BDNF), excess proinflammatory cytokines, mental fatigue from lack of cellular energy, Alzheimer’s, Parkinson’s, stroke and more can all cause anxiety and depression. Here are a few nootropics that can help lift your mood, and quell the anxiety. But realize this is by no means an exhaustive list. These are what I’ve found work for me. They may work for you too. And if your depression or anxiety is severe, please, please seek professional help while you’re exploring your nootropic options. •

Aniracetam 750 mg twice per day. This member of the racetam-family of nootropics, Aniracetam is very well known for helping anxiety and depression. And one of my favorites. Aniracetam activates D2 and D3 dopamine receptors in your brain. Reducing anxiety and improving cognition, learning, memory and mood. I have used Aniracetam every day for the last 10 years. And can’t imagine doing without it.

•

Alpha GPC 300 mg 3-times per day or CDP-Choline 300 mg twice per day. Both nootropics help boost acetylcholine (ACh) in your brain. ACh is associated with focus, concentration, memory, mood and learning. And the choline each provides is needed when using any racetam (like Aniracetam).

•

Ashwagandha 250 - 500 mg per day. Used for thousands of years in Ayurvedic medicine, Ashwagandha helps relieve stress, fatigue, restores energy and concentration, and normalizes blood sugar.

•

Bacopa Monnieri 45% bacosides is 450 mg per day. Bacopa Monnieri is believed by some to be the best nootropic available today. This adaptogen helps prevent chemical and physical stress instead of suppressing them like many modern antidepressants.

•

Lemon Balm 300 mg twice per day. This plant from the mint family, Lemon Balm inhibits the GABA transaminase enzyme. Which in turn helps maintain adequate levels of GABA in your brain. Resulting in a calming effect and relieving anxiety and depression.

•

Rhodiola Rosea 150 - 200 mg per day. Rhodiola increases AMPK which helps decrease depression and stress-related mood swings, reduces fatigue, stimulates energy and alertness and boots cognition.

•

Sulbutiamine 400 mg twice per day. Synthesized in the lab from Vitamin B1 (thiamine), Sulbutiamine is another favorite of mine because it boosts memory, motivation and is a great antidepressant. I can’t imagine going a day without my 2-doses of Sulbutiamine.

•

Vitamin B6 up to 100 mg per day. Vitamin B6 is a required coenzyme for the synthesis of most major neurotransmitters in your brain. And helps enhance alertness, cognition, energy, memory

and mood. •

Vitamin B12 100 mcg per day. Vitamin B12 is essential for the synthesis of DNA, RNA and neurotransmitters in your brain. B12 enhances alertness, cognition, memory, decision-making and mood.

Note that you don’t need every nootropic listed here to alleviate your anxiety and depression. In fact, using everything on this list could do more harm. The key is to experiment through trial and error until you find what works best for you. Experiment, and find your favorites. Each supplement is readily available at your local vitamin shop or online. Go for purity and organic if possible. The only nootropics in this stack I’d suggest you use no matter what else you choose are Alpha GPC or CDP-Choline and the B-Vitamins. Make shopping for Cheerios fun again.

Best Nootropics for Energy (physical & mental) & Motivation If you’ve ever felt mentally drained after writing an exam, an intense study session, a misunderstanding with your partner, or working out a business problem -- nootropics can help. Energy and motivation kinda’ go hand-in-hand in my book. When I’m energized, it usually translates into motivation to get things done. When energy stores are depleted in my brain and body, I’m burned out and nothing much is going to happen. Mental fatigue has a variety of causes. Depleted neurotransmitters can cause fatigue as well as a host of other issues. A lack of Adenosine Triphosphate (ATP) which is the energy source for brain cells is another cause of mental fatigue. And leads to neurodegenerative disease. Hormones that are out of balance or deficient can cause fatigue. And poor cerebral blood flow which provides oxygen and nutrients to brain cells can result in fatigue. The amount of available mental energy has a direct influence on cognitive and mental performance. Let’s look at the nootropics that can fix mental fatigue and boost motivation. •

Acetyl L-Carnitine (ALCAR) 500 mg twice per day. ALCAR boosts acetylcholine (ACh) and transports fatty acids through cell membranes into mitochondria for brain cell energy production. One of my favorite nootropics, ALCAR increases memory, mental alertness, fluid thought and is a powerful antioxidant. If you decide to try ALCAR, use it with Alpha GPC or CDP-Choline for best results.

•

CoQ10 & Ubiquinol 200 mg per day. CoQ10 is essential for producing Adenosine Triphosphate (ATP) which is made within mitochondria in brain cells. Improving athletic performance, works as an antioxidant, and battles fatigue and depression. Ubiquinol should be part of every nootropic stack. Particularly if you’re over 40.

•

Alpha Lipoic Acid 100 mg twice per day. The natural form R-Lipoic Acid functions as a cofactor for mitochondrial enzymes involved in energy production.

•

Creatine up to 5 grams per day. Creatine acts as fuel for cells. Including your brain cells. And provides ‘energy on demand’ when you need it. Creatine is a favorite of nootropic users because of the fuel demanded by brain cells especially under physical or mental stress. After crossing your blood-brain barrier, creatine binds to phosphate. Creatine phosphate in turn fuels energy production for your brain.

•

NADH 5 – 20 mg per day. NADH is a coenzyme used in the formation of Adenosine Triphosphate (ATP), the energy source produced within mitochondria in your brain cells. NADH boosts alertness, mental performance, energy, and memory.

•

PQQ 10 – 20 mg per day. PQQ helps create mitochondria in your brain cells. When cellular energy gets a boost, you can experience better and faster thinking, learning is easier, recall is faster, and you’ll be more resistant to fatigue.

•

Rhodiola Rosea 150 - 200 mg per day. Rhodiola Rosea increases AMPK which triggers the use of stored energy from fats in your brain cells. Boosting alertness, energy and cognition while decreasing depression and stress-related mood swings.

•

Ginseng 500 mg twice per day. Ginseng boosts ATP production within mitochondria for more energy. It helps improve mood and reduce stress. Ginseng works as an adaptogen, reduces adrenal fatigue, and boosts GABA use for an anti-stress benefit.

For a pure, clean energy boost try combining R-Lipoic Acid, ALCAR, CoQ10 and PQQ twice per day. Experiment and find out what works best for you to raise your energy and motivation levels.

Best Nootropics for Brain Repair and Maintenance According to the American Center for Disease Control (CDC) an estimated 1.7 million in the US suffer from Traumatic Brain Injury every year. 1408 And that’s just for the USA. This is clearly a world-wide problem for the human race. Brain injury covers a lot of territory and includes concussion, Post Stroke Syndrome, sports and athletic injuries, damage from pharmaceuticals, environmental toxins, bad food and water, polluted air and more. The mechanics of injury can affect cerebral blood flow, torn tissue, damage to neurons, altered brain waves and neurotransmitters, free radical and oxidative damage and more. Now the “official” line from the FDA and other governmental authorities in the USA and many countries world-wide, nootropic supplements and other ‘natural’ substances cannot repair brain injury.

While this is certainly not medical advice, and you should absolutely seek professional medical help for brain injury, neurohackers have found relief on their own experimenting with nootropics. Here’s a small sample of what we’ve found useful. •

CDP-Choline. CDP-Choline provides your brain with choline which aids in the synthesis of acetylcholine (ACh). And cytidine in CDP-Choline converts to uridine which is important for neural membrane synthesis.

•

DHA (Omega 3). DHA makes up a large portion of your brain’s gray matter. This fatty acid helps form cell membranes, neurons and synapses which are needed to form and encode memories.

•

Phosphatidylcholine (PC). PC is a phospholipid which helps build and repair brain cell membranes.

•

PQQ. The enzyme cofactor PQQ facilitates the growth of new mitochondria in your brain cells. Boosting the production of nerve growth factors in cells that support creation of new neurons. And reduces inflammation and oxidative stress.

•

Pterostilbene. Found in cranberries, blueberries, and grapes, Pterostilbene is a potent antioxidant, stimulates Brain-Derived Neurotrophic Factor (BDNF), and promotes neuroplasticity. By reducing oxidative stress, Pterostilbene not only helps repair your brain, but also helps prevent heart attacks and stroke.

•

Resveratrol. This polyphenol antioxidant found in the skin of grapes, Resveratrol improves blood flow and reduces inflammation. Improving cell survival and neurogenesis in the hippocampus, resulting in better memory and learning.

•

Turmeric. Turmeric is unique in its ability to reduce inflammation common to Parkinson’s, Alzheimer’s and brain tumors.

Now there’s a temptation to throw everything into this nootropic stack if you’re having real problems with brain damage. But once again caution is advised. Work with a professional neurologist while you’re experimenting and exploring your nootropic options. All the nootropics on this list are safe to use within recommended doses. But each of us has unique brain and body chemistry. And each of us will react differently to everything on this list. These are general guidelines on what we’ve found to work with brain repair. And maintaining a healthy brain. Start with low doses of three or four from the list. See how your body and brain reacts. And continue to experiment. Try new nootropics until you find your ideal stack.

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HOW TO CREATE THE BEST NOOTROPIC STACK If you’ve spent any time on my website NootropicsExpert.com or YouTube channel, or have experimented with nootropics before, you have a good idea how certain nootropic supplements can benefit your brain. But if you’re just getting started with nootropics, the choices can seem overwhelming. Where do you start? Allow me a minute or two to share my story. How I discovered nootropics. And how I ended up with the nootropic stack I’m using now. About sixteen years ago my wife introduced me to her psychiatrist. My career and relationship were on rocky ground, and she was desperate. So was I. What happened next was nothing short of a miracle to my mind. Within 10 minutes this very wise and knowledgeable man diagnosed me as Adult ADD. This of course was news to me. But what happened as a result of that first meeting was a complete life change. This doctor prescribed Ritalin. From the first day it was like someone had flipped the switch. And turned the lights on in my brain. For the first time in my adult life I could focus. My thinking became clearer. This complete transformation lasted for about 7 years. But Ritalin wasn’t as effective for ADD symptoms as it was in the beginning. I had been diagnosed as hypothyroid a couple of years prior. The brain fog and fatigue were taking its toll on my career and marriage again. We tried switching to Adderall and it didn’t work. By then I’d learned enough about how my brain worked. Had a good idea what was wrong. And decided to go the “natural” route with nootropics. I discovered a pre-formulated nootropic stack that helped me avoid going back on stimulants. My life started to turn around and continued to get better as I experimented with other nootropics. I continue to use that pre-formulated nootropic stack (which I’ll tell you about in a minute). My current daily nootropic stack is constantly evolving the more I learn.

The Most Effective Nootropic Stack for You So what’s your story? What are you trying to do with nootropics?

If you are a university student, an entrepreneur, a business executive, a stay-at-home mom, or dad, or a senior – what are you trying to improve? It could be just one thing you want to work on. Like improving your memory. Maybe you have a difficult time focusing like I did. Or you find learning new material, a skill or language an insurmountable problem. You could have an issue with anxiety, or bouts of depression. Procrastination could leave you feeling like a failure because of a lack of motivation. For many of us, it’s more than just one problem we’re trying to fix. In my case, the combination of ADD and hypothyroidism caused problems with anxiety, cognition, focus, memory, and depression. That’s a lot to deal with and a lot to fix.1409, 1410 The good news is it’s entirely possible with the right combination of nootropics to address each of these issues. My life is a good example of what’s possible with the right nootropic stack. I’m deeply grateful for doing extremely well in my career. My marriage is better than I ever dreamed possible. And my future looks amazing. But where do you start? If you’re trying to fix one thing, like memory or depression, it narrows the list of nootropics down to something more manageable. But to be perfectly honest with you, one nootropic that works for me, may not work as well for you. Each of us have unique brain “wiring”. Our chemical makeup is different. And is affected by foods we eat, where we live, the air we breathe, the genes we inherited from our parents, and more. So experimentation is key. Pick your top choice of something you’d like to improve. Once you find something that works reasonably well, go to the next thing on your list. With time, effort, and diligent experimenting you’ll find the perfect nootropic stack for you.

Your First Nootropic Stack My recommendation is to create your own nootropic stack when starting out. Tailor your stack to each issue your trying to solve. It’ll likely be more expensive because you need to get each individual nootropic or supplement. The advantages at first outweigh the cost in my opinion. When you find something that works, you then need to figure out how much of that nootropic works best with your brain and body. If you try something and it doesn’t work as well as expected, or what you were promised in the marketing hype, or what you read on the forums – pitch it. And try something else.

Flexibility and experimentation is key when you’re getting started with nootropics. A pre-formulated stack doesn’t allow that flexibility. Keep that option in reserve until you nail down what works best for you. Then look for a nootropic stack that fills all your requirements. Let’s briefly look at some of your options for major issues to get you started. This is by no means an exhaustive list but a way to point you in the right direction. Use the search function on NootropicsExpert.com to find every nootropic that works for memory, or depression, or anxiety, or whatever it is you need to fix.

Nootropics for Cognition, Thinking and Decision-Making Cognition is the mental action or process you go through when learning something new and understanding it through thought, experience, and your physical senses.1411 Cognition includes thinking, knowing, short-, working-, and long-term memory, decision-making and problem solving. That’s a tall order to cover and will likely take more than one nootropic. You can start with: •

Alpha GPC 300 mg 3-times per day or CDP-Choline 300 mg twice per day. Both nootropics help boost acetylcholine (ACh) in your brain. ACh is associated with memory and learning.

•

Acetyl L-Carnitine (ALCAR) 500 mg twice per day. ALCAR boosts acetylcholine (ACh) and transports fatty acids through cell membranes into mitochondria for brain cell energy production. One of my favorite nootropics, ALCAR increases memory, mental alertness, fluid thought and is a powerful antioxidant. If you decide to try ALCAR, use it with Alpha GPC or CDP-Choline for best results.

•

Lion’s Mane Mushroom 1,000 mg twice per day. Lion’s Mane extract increases Brain Nerve Growth Factor or neurogenesis. Improving attention, focus, thinking, depression, anxiety, and helps repair damaged neurons.

•

L-Tyrosine 500 mg twice per day. L-Tyrosine is a precursor to the creation of dopamine in your brain. More dopamine helps improve alertness, focus, working memory and executive function (decision-making).

•

B-Complex. The B-Vitamins are required coenzymes for the synthesis of all the major neurotransmitters in your brain. And help enhance alertness, cognition, energy, memory and mood.

Nootropics for Memory We use several different types of memory every day. Short-term memory is also known as primary or active memory. And is limited to what you remember for 20 to 30 seconds.

Long-term memory is the type of memory associated with an event or information you acquired long ago. This is a complicated form of memory influenced by your perception of an event or thing, conditioning, or any other input. And is encoded using long-term potentiation and strengthening neurons and synapses. Working memory is distinct from short-, and long-term memory. These are memories that are not only remembered, but simultaneously processed with information that is important to you. You remember the purpose of the information, and why you decided to remember it.1412 Each type of memory can be assisted by different nootropics. Because neurotransmitters, cerebral blood flow, long-term potentiation, hormones and more all come into play for memory. • • • • • •

•

Alpha GPC or CDP-Choline. Both nootropics help boost acetylcholine (ACh) in your brain. ACh is associated with memory and learning. DHA (Omega 3). DHA makes up a large portion of your brain’s gray matter. This fatty acid helps form cell membranes, neurons, and synapses which are needed to form and encode memories. Huperzine-A. Hup-A helps promote memory by increasing acetylcholine levels. L-Theanine. Found naturally in green tea and available as a nootropic supplement, L-Theanine helps boost dopamine and serotonin. Improving anxiety, focus, learning, and mood. Noopept. Noopept stimulates dopamine, nicotinic and serotonin receptors in your brain. Boosting cognition, memory, retention, logical thinking, improving your reflexes and mood. Phosphatidylserine (PS). PS is vital for brain health. Highly concentrated in cell membranes, PS helps in the release, storage and activity of neurotransmitters and receptors. Boosting cognition, focus, memory and recall. Piracetam. The original nootropic, Piracetam influences AMPA and NMDA receptors in your brain. Affecting learning and memory.

Nootropics for Anxiety and Depression Do you remember what it used to be like to be in a ‘good mood’ all of the time? Anxiety and depression are something most of us have had to deal with at one time of another. For me, being ADD and hypothyroid was like a double whammy. And it took a while to dig out of the hole I was in. Anxiety1413 and depression1414 are often ‘grouped’ together both in nootropic circles as well as in the psychiatric/medical world. But they are two distinctly different conditions. Even though the cause of anxiety and depression may overlap. All kinds of conditions can contribute to anxiety and depression. Neurotransmitter levels that are out of balance can cause severe depression. Illness and stress can cause anxiety and depression. Poor cerebral blood flow, a lack of Brain-Derived Neurotrophic Factor (BDNF), mental fatigue from lack of cellular energy, Alzheimer’s, Parkinson’s, stroke and more can all cause anxiety and depression.’ Here are a few nootropics that can help. This is by no means an exhaustive list.

And if your depression or anxiety is severe, please, please seek professional help while you’re exploring your nootropic options. •

•

•

•

•

•

•

•

•

Aniracetam 750 mg twice per day. This member of the racetam-family of nootropics, Aniracetam is very well known for helping anxiety and depression. And one of my favorites. Aniracetam activates D2 and D3 dopamine receptors in your brain. Improving anxiety, cognition, learning, memory and mood. Alpha GPC 300 mg 3-times per day or CDP-Choline 300 mg twice per day. Both nootropics help boost acetylcholine (ACh) in your brain. ACh is associated with memory and learning. And requires the cofactor Acetyl L-Carnitine (ALCAR) for acetylcholine synthesis. Acetyl L-Carnitine (ALCAR) 500 mg twice per day – a required cofactor for acetylcholine synthesis and works with Alpha GPC and CDP-Choline – helps transport of fatty acids into mitochondria to make ATP for more energy – it also boosts brain-derived neurotrophic factor (BDNF) needed for cell repair and neurogenesis Ashwagandha 250 – 500 mg per day. Used for thousands of years in Ayurvedic medicine, Ashwagandha helps relieve stress, fatigue, restores energy and concentration, and normalizes blood sugar. Bacopa Monnieri 45% bacosides is 450 mg twice per day. Bacopa Monnieri is believed by some to be the best nootropic available today. This adaptogen helps prevent chemical and physical stress instead of suppressing them like many modern antidepressants. Lemon Balm 200 - 400 mg twice per day. This plant from the mint family, Lemon Balm inhibits the GABA transaminase enzyme. Which in turn helps maintain adequate levels of GABA in your brain. Resulting in a calming effect and relieving anxiety and depression. Rhodiola Rosea 150 - 200 mg per day. Rhodiola Rosea increases AMPK which helps decrease depression and stress-related mood swings, reduces fatigue, stimulates energy and alertness and boots cognition. Sulbutiamine 400 mg twice per day. Synthesized in the lab from Vitamin B1 (thiamine), Sulbutiamine is another favorite of mine because it boosts memory, motivation and is a heck of an antidepressant. B-Complex. The B-Vitamins are required coenzymes for the synthesis of all your major neurotransmitters. And helps enhance alertness, cognition, energy, memory and mood.

Nootropics for Energy and Motivation If you’ve ever felt mentally drained after writing an exam, an intense study session, a misunderstanding with your partner, or working out a business problem -- nootropics can help. Energy and motivation kinda’ go hand-in-hand in my book. When I’m energized, it usually translates into motivation to get things done. When energy stores are depleted in my brain and body, I’m burned out and nothing much is going to happen. Mental fatigue has a variety of causes. Depleted neurotransmitters can cause fatigue as well as a host of other issues. A lack of Adenosine Triphosphate (ATP) which is the energy source for brain cells is

another cause of mental fatigue. And leads to neurodegenerative disease. Hormones that are out of balance can cause fatigue. And poor cerebral blood flow which provides oxygen and nutrients to brain cells can result in fatigue. The amount of available mental energy has a direct influence on cognitive and mental performance. Let’s look at the nootropics that can fix mental fatigue and boost motivation. •

•

• •

•

•

•

•

Acetyl L-Carnitine (ALCAR) 500 mg twice per day. ALCAR boosts acetylcholine (ACh) and transports fatty acids through cell membranes into mitochondria for brain cell energy production. One of my favorite nootropics, ALCAR increases memory, mental alertness, fluid thought and is a powerful antioxidant. If you decide to try ALCAR, use it with Alpha GPC or CDP-Choline for best results. CoQ10 & Ubiquinol 200 mg per day. CoQ10 is essential for producing Adenosine Triphosphate (ATP) which is made within mitochondria in brain cells. Improving athletic performance, works as an antioxidant, and battles fatigue and depression. Ubiquinol should be part of every nootropic stack. Particularly if you’re over 40. Alpha Lipoic Acid 100 mg twice per day. The natural form R-Lipoic Acid functions as a cofactor for mitochondrial enzymes involved in energy production. Creatine up to 5 grams per day. Creatine acts as fuel for cells. Including your brain cells. And provides ‘energy on demand’ when you need it. Creatine is a favorite of nootropic users because of the fuel demanded by brain cells especially under physical or mental stress. After crossing your blood-brain barrier, creatine binds to phosphate. Creatine phosphate in turn fuels energy production for your brain. NADH 5 – 20 mg per day. NADH is a coenzyme used in the formation of Adenosine Triphosphate (ATP), the energy source produced within mitochondria in your brain cells. NADH boosts alertness, mental performance, energy, and memory. PQQ 10 – 20 mg per day. PQQ helps create mitochondria in your brain cells. When cellular energy gets a boost, you can experience better and faster thinking, learning is easier, recall is faster, and you’ll be more resistant to fatigue. Rhodiola Rosea 150 - 200 mg per day. Rhodiola Rosea increases AMPK which triggers the use of stored energy from fats in your brain cells. Boosting alertness, energy and cognition while decreasing depression and stress-related mood swings. Ginseng 500 mg twice per day. Ginseng boosts ATP production within mitochondria for more energy. It helps improve mood and reduce stress. Ginseng works as an adaptogen, reduces adrenal fatigue, and boosts GABA use for an anti-stress benefit.

For a pure, clean energy boost try combining R-Lipoic Acid, ALCAR, CoQ10 and PQQ twice per day. Experiment and find out what works best for you to raise your energy and motivation levels.

Nootropics for Brain Repair and Maintenance According to the American Center for Disease Control (CDC) an estimated 1.7 million in the US suffer from Traumatic Brain Injury every year.1415

And that’s just for the USA. This is clearly a world-wide problem for the human race. Brain injury covers a lot of territory and includes concussion, Post Stroke Syndrome, sports and athletic injuries, damage from pharmaceuticals, environmental toxins, bad food and water, polluted air and more. The mechanics of injury can affect cerebral blood flow, torn tissue, damage to neurons, altered brain waves and neurotransmitters, free radical and oxidative damage and more. Now the “official” line from the FDA and other governmental authorities in the USA and many countries world-wide, nootropic supplements and other ‘natural’ substances cannot repair brain injury. While this is certainly not medical advice, and you should absolutely seek professional medical help for brain injury, neurohackers have found relief on their own experimenting with nootropics. Here’s a small sample of what we’ve found useful: •

•

•

•

•

•

•

CDP-Choline 300 mg twice per day. CDP-Choline provides your brain with choline which aids in the synthesis of acetylcholine (ACh). And cytidine in CDP-Choline converts to uridine which is important for neural membrane synthesis. DHA (Omega 3) 1,000 mg per day. DHA makes up a large portion of your brain’s gray matter. This fatty acid helps form cell membranes, neurons, and synapses which are needed to form and encode memories. Phosphatidylserine (PS) – 100 mg 3-times per day – works with DHA for brain cell membrane repair and maintenance – some consider to be the most potent nootropic on the planet and if you read my review earlier in this book, you’ll see why PQQ 10 mg twice per day. The enzyme cofactor PQQ facilitates the growth of new mitochondria in your brain cells. Boosting the production of nerve growth factors in cells that support creation of new neurons. And reduces inflammation and oxidative stress. Pterostilbene 50 mg per day. Found in cranberries, blueberries, and grapes, Pterostilbene is a potent antioxidant, stimulates Brain-Derived Neurotrophic Factor (BDNF), and promotes neuroplasticity. By reducing oxidative stress, Pterostilbene helps prevent heart attacks and stroke. Resveratrol 250 mg per day. This polyphenol antioxidant found in the skin of grapes, Resveratrol improves blood flow and reduces inflammation. Improving cell survival and neurogenesis in the hippocampus, resulting in better memory and learning. Turmeric. 650 mg (95% curcuminoids) 3-times per day. Turmeric is unique in its ability to reduce inflammation common to Parkinson’s, Alzheimer’s and brain tumors. Boost it’s bioavailability by pairing this supplement with 10 mg BioPerine.

Conclusion There are many ways to address each issue you’re dealing with when it comes to optimizing brain health and function. If you’re a nootropic veteran I’m sure, you’ll find holes in my recommendations. Each section is most

definitely not a conclusive list of nootropics for a single condition. I encourage you to visit and use the “Search” function on my website NootropicsExpert.com or YouTube channel. Enter the issue you’re dealing with, and you’ll get a list of articles or videos with suggestions for your nootropic stack. There are a lot of ‘nootropics’ websites out there. And the last truly authoritative books written on the subject were published in 1993. So it can get very confusing and overwhelming. Especially if you’re just starting out with nootropics and brain optimization. My intention with NootropicsExpert.com, and for this book, was to collate as much good information in one place as I could find. To make it easier for anyone at any level of expertise. But one strong word of caution when experimenting with new nootropic supplements. For example, by no means should you include everything listed under “memory” in your stack. One or two options from each section can help you toward your ideal nootropic stack. Many nootropics work synergistically and together can make a more powerful solution than a single nootropic supplement on its own. When combining several nootropics into what we call a “stack” you’ll want to back off to the lowest recommended dose of each to start.

My Nootropic Stack Early in this chapter I promised to reveal the pre-formulated stack that I used to replace prescription stimulants for Adult ADD. After experimenting with many of the well-known stacks, I settled on Mind Lab Pro®. Mind Lab Pro® contains therapeutic dosages of 11 top quality natural nootropic ingredients I’ve included in this book. I’ve found it less expensive to use this stack than buying each nootropic on its own. All I’ve had to add is unrefined coconut oil, DHA, magnesium, Vitamin D, Aniracetam and Sulbutiamine. If you have questions about building your perfect nootropic stack, I encourage you to post a question in the comments section on the relevant article or review at NootropicsExpert.com or in the comments section of my YouTube channel. I or another experienced neurohacker in our community will help you out.

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NOOTROPICS GLOSSARY Acetylcholine Acetylcholine (ACh) is the acetic ester of choline, and is a neurotransmitter. ACh is found throughout your body. But in nootropics we typically refer to acetylcholine function in the Central Nervous System and specifically the brain.1416 Some nootropics upon entering your brain separate into compounds that can make acetylcholine. Others may increase the uptake of acetylcholine in the brain. Acetylcholine’s function in the brain is critical for encoding new memories, reasoning, concentration, cognition, and growth of new synapses (neuroplasticity). Lack of acetylcholine can result in diseases like ADD, ADHD and Alzheimer’s.

Adaptogen Adaptogens are a class of herbs that help the body adapt to stress, and exert a normalizing effect in your body. As a nootropic, adaptogens can help strengthen mental fortitude, and can help maintain active, energized thinking in response to the brain-dulling effects of prolonged stress. Adaptogens are valued for their ability to boost endurance and physical performance. Examples of adaptogens popular in the nootropic community include Rhodiola and Ashwagandha.

Adenosine Triphosphate (ATP) Adenosine Triphosphate (ATP) is the “energy currency of life”. ATP is a coenzyme that is synthesized in the energy factories called mitochondria within each of your brain cells. Adequate levels of ATP are crucial for peak brain performance. As we age, blood flow to the brain decreases and ATP production declines. If your brain cells don’t have an adequate supply of ATP, they die.

Advanced Glycation End Products (AGEs) AGEs form in your body when proteins or fats combine with sugars (glycation). This can harm the normal function of cells, making them more susceptible to damage and premature aging. Your body can naturally rid itself of harmful AGEs, but it doesn’t eliminate them effectively when too many are ingested through food. The accumulation of AGEs has been linked to aging, chronic illness, and cardiovascular, liver and Alzheimer’s disease.

Age-Related Cognitive Decline Studies have shown the aging brain undergoes a loss of grey and white matter volumes in the brain.1417 This has become one of the biggest health threats of this century. And it’s primarily because we’re living longer.

It manifests as brain fog, memory problems, verbal communication declines, cognition slows down, and eventually could develop into dementia or Alzheimer’s Disease. Many nootropics help prevent and often reverse the effects of Age-Related Cognitive Decline.

Agonist An agonist is a chemical substance in your body that is capable of activating a neuroreceptor to induce a full or partial response.

Alkaloid An alkaloid is typically of plant origin. It contains nitrogen which gives an alkaline (pH value greater than 7.0) reaction when mixed with a solution such as water. Many alkaloids cause pharmacological effects in humans. Alkaloid substance names generally end in “-ine”. Examples are caffeine, morphine, quinine and nicotine.

Amino Acids Amino acids are used in every cell of your body and are used to form proteins. Amino acids give cells their structure, transport and store nutrients, and influence the function of arteries, glands, organs and tendons. They repair tissue and remove waste from cells. Scientists have discovered about 50 amino acids. Only 20 are used to make proteins in your body. Of those 20, 9 are defined as essential. Meaning your body needs to get them from sources outside the body like food. The other 11 can be synthesized within your body. Essential Amino Acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine. Nonessential Amino Acids: Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine and Tyrosine.

Amyloid Plaques & Neurofibrillary Tangles Amyloid Plaques are accumulations of protein fragments that have clumped together in the space between brain neurons. This prevents normal brain function. And is strongly indicated in the formation of Alzheimer’s Disease. Neurofibrillary Tangles are found within brain cells. In microtubules necessary for interaction with brain cells. When these microtubules collapse, twisted fibers of these proteins are called Neurofibrillary Tangles. And are also strongly indicated in the formation of dementia and Alzheimer’s Disease.

Ampakines Ampakines are nootropics that modulate AMPA receptors in your brain. These receptors work like control channels, overseeing and regulating synaptic transmissions.

Ampakines seem to adjust neuroreceptors in order to allow them to work as needed rather forcing them. The result of this action is a stimulant-like effect without any of the negative side effects associated with stimulants (i.e. nervousness, insomnia). Many racetams could be considered Ampakines.

AMPA Receptors The AMPA receptor is paired with an ion channel so that when glutamate binds to this receptor, the channel lets sodium ions enter that neuron. This sodium causes the dendrite of that neuron to become locally depolarized. Once this depolarization reaches a critical threshold, it triggers an action so this nerve impulse is transmitted to the next neuron.

Antagonist An antagonist is a chemical substance in your body which counteracts or blocks the effects of another substance. For example, an antagonist at a neuroreceptor blocks or lowers the activity of that receptor.

Anxiolytics Anxiolytics are anti-anxiety natural nootropic supplements, or prescription drugs used to prevent anxiety.

Apoptosis Apoptosis is ‘programmed cell death’ in your body and brain. If cells are no longer needed, they commit suicide. In a healthy adult human, billions of cells die in various parts of your body every hour for different reasons. But mainly to maintain homeostasis within that organ or body tissue. When apoptosis is disrupted, disease happens. Cancer is a classic example of cell proliferation gone awry.

Attention Deficit Disorder ADD is officially called Attention-Deficit/Hyperactivity Disorder, or AD/HD (American Psychiatric Association, 1994). This disease is divided into three subtypes; inattentiveness, impulsivity, and hyperactivity. Scientific evidence suggests that the disorder is genetically transmitted in many cases. And results from a chemical imbalance or deficiency in certain neurotransmitters.1418 ADD is characterized by a person’s inability to complete tasks and process information at normal rates. The abnormal function of the neurotransmitter dopamine is usually implicated in this disease.

Attention Deficit/Hyperactivity Disorder See Attention Deficit Disorder.

Axons Each neuron in your brain can have thousands of dendrites, but only one axon. The neuron uses its axon

to transmit an action potential (electrochemical signal) down the length of the axon. With the intent of finding neighboring neuron’s dendrites to communicate with.

Ayurveda Ayurveda is the traditional Hindu system of medicine practiced for thousands of years in India. It is based on the ideal balance of bodily systems and uses diet, herbal treatments and yoga.

Benzodiazepines Benzodiazepines are a class of psychoactive drugs used to treat anxiety, insomnia, panic attacks, and other conditions. Benzodiazepines work by enhancing the effect of the neurotransmitter GABA which is responsible for governing the activity of neurons related to stress and anxiety. Well known benzodiazepines include Valium, Klonopin and Xanax.

Bioavailability Bioavailability is the proportion of the nootropic or other substance that once it enters your body’s circulation, is able to have an effect. And is not just eliminated as waste.

Blood-brain Barrier The blood-brain barrier is made up of a layer of endothelial cells that when functioning properly, allows precise control over the substances that enter or leave the brain. The blood-brain barrier’s main function is to protect the brain from things that may injure it. In the world of nootropics, we’re interested in substances and compounds that easily cross the blood-brain barrier. Or what needs to be added to help it cross.

Brain-Derived Neurotrophic Factor (BDNF) Neurotrophic factors are a family of proteins that are responsible for the growth and survival of nerve cells. In the brain they’re called brain-derived neurotrophic factor and the brain nerve cells are called neurons. In the brain, BDNF is released by either a nerve cell or a support cell, such as an astrocyte, and then binds to a receptor on a nearby nerve cell. This binding results in the production of a signal which can be transported to the nucleus of the receiving nerve cell. There, it prompts the increased production of proteins associated with nerve cell survival and function.1419

Brain waves The brain is an electrochemical organ. Researchers speculate that a fully functioning brain can generate as much as 10 watts of electrical power. So brain waves are an electrical impulse in the brain.1420 Brain waves occur when neurons send signals between each other. There are several different types of brain waves. But the main ones are Beta, Alpha, Theta, and Delta.

Beta waves are the most rapid pattern. And are associated with concentration, arousal, alertness and cognition. You experience Alpha waves as you become more relaxed. The brain waves slow into an Alpha wave pattern. Associated with super-learning, flow states and joy. Still slower brain wave patterns are Theta waves. Often experienced by meditators. When you’re dreaming at night, you’re making Theta waves. Theta waves are associated with creativity, “integrative experiences” and relief from trauma. An “ah-ha moment” is a burst of Theta waves in your brain. The slowest of all brain wave patterns are Delta Waves. They are generally associated with dreamless sleep. Very advanced meditators are able to remain alert in this deep, trance-like state. Delta waves are associated with leadership, persuasion, achievement and Oneness.

Catecholamines Catecholamines are amines derived from the amino acid tyrosine. In nootropics we focus mostly on dopamine, epinephrine (adrenaline), and norepinephrine which act as hormones or neurotransmitters.

Central Nervous System The central nervous system is the entire accumulation of nerves in the brain and spinal cord. This nerve “highway” uses neurons to send and receive information throughout your body. And is protected by cerebrospinal fluid (CFS).

Cerebral The word “cerebral” gets its meaning from cerebrum, which is Latin for brain.

Cerebral Circulation Cerebral Circulation refers to the way blood flows, or circulates, in the brain. Cerebral circulation is your brain’s source for the healthy exchange of oxygen and nutrients needed to function properly.

Chronic Fatigue Syndrome (CFS) Chronic Fatigue Syndrome (CFS) is a disorder that causes extreme ongoing fatigue. Not the kind of fatigue that goes away after you rest. Symptoms last for 6 months or more. And is characterized by a general feeling of being unwell, muscle pain, memory problems, pain in multiple joints, headaches and sleep problems. CFS is often treated medically with stimulants like Adderall.

Circadian Rhythm Circadian rhythm is your 24-hour built-in body clock. It can be affected by external cues like light and temperature. Circadian rhythms are critical in determining your sleeping and eating patterns. Patterns in brain wave

activity, hormone production and other biological processes in your body are linked to this daily cycle.

Cognition Cognition is the mental action or process of acquiring knowledge and understanding through thought, experience and the senses. Cognition includes thinking, knowing, memory, decision-making and problem solving.

Concentration Concentration is defined as the action or power of focusing your attention or mental effort. Without distractions or interference. Certain nootropics can help to bolster your enthusiasm, skill and commitment towards your desired goal.

Coenzyme A coenzyme is an organic molecule (nonprotein) that binds with a protein to form an active enzyme. By themselves, coenzymes cannot catalyze a reaction, but can help enzymes to. Vitamins B1, B2 and B6 can serve as coenzymes.

Cortex In your brain, the cortex is the outer layer of gray matter covering the cerebral hemispheres. It is understood to be the area of higher mental functions such as cognition, intellect, and volition.

Cyclic Adenosine Monophosphate (cAMP) Cyclic Adenosine Monophosphate (cAMP) is a derivative of adenosine triphosphate (ATP) and is used for intracellular signaling. In the brain, cAMP affects the function of higher-order thinking in the prefrontal cortex. It is thought to play an important role in the formation of memories. In theory, by boosting cAMP, you can increase memory function and optimize overall brain performance.

Cycling Tolerance is a problem with some nootropics. Consistent non-stop use can cause their effectiveness to diminish over time. It is also possible for some nootropic users to develop a psychological dependence (addiction) to compounds from prolonged use. Even though there is no physical addiction or withdrawal symptoms. One way to circumvent or avoid tolerance or dependence is to “cycle” the use of certain nootropics. Find out what the tolerance characteristics (if any) are for each of the nootropics you are using. And develop a schedule to stop their use for a short period of time. For example, you could use Huperzine-A for 5 days at the recommended dose and take a break for 2 days.

DNA (deoxyribonucleic acid) DNA is located in each of your cell’s nucleus (cellular DNA). A small amount of DNA is also found in the mitochondria within each cell (called mitochondrial DNA or mtDNA). And is stored as code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is kind of like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.

Demethylation Demethylation is the removal of a methyl group from a molecule.

Dendrites Dendrites are like branches projecting out of neurons that act like an antenna. Dendrites receive electrical signals sent by the synapses of neighboring neuron axons. You can have as many as 15,000 dendrites projecting from a single neuron. When you experience incoming stimuli from your senses, neuron activity increases. And dendritic spines change size, shape and conduction leading to long-term potentiation (LTP). This change in dendritic spines (neuroplasticity) and long-term potentiation plays a fundamental role in learning and memory.

Dopamine Dopamine is a neurotransmitter that serves as a chemical signal or messenger between neurons (brain nerves). When it’s released from the first neuron, it travels into the space (synapse) between the two neurons. And bumps up against receptors on the second neuron. Dopamine has five receptor types it interacts with. But is mostly associated with “feel good” or reward behavior life sex, drugs and rock and roll. Dopamine also aids in memory formation, learning and retention, attention and focus, cognition, and sleep. Insufficient levels of dopamine are associated with anxiety, Attention Deficit Disorder (ADD) and Parkinson’s Disease.

Downregulation Downregulation is a process in your brain where the amount of activity in a particular neuron receptor decreases. This typically happens in response to abnormally high activity in response to one particular drug or nootropic. In other words, too much of one nootropic all at once. Or for an extended period of time.

Encoding Before information can be stored as memories, it first needs to be encoded. Encoding is the conversion of information into a form the brain can use. There are 3 types of encoding: 1. Acoustic encoding is when you use sound to record information. 2. Visual encoding is when a person uses mental images to remember something. 3. Semantic encoding is when you remember the actual meaning or significance of information. Semantic encoding is the most important part of long term memory encoding.

Epinephrine Epinephrine is also called adrenaline. Epinephrine is typically released in response to acute stress (fight or flight response). This hormone is secreted mainly by the adrenal glands. In the medulla region of the adrenals, the amino acid tyrosine is transformed into norepinephrine. Through a complex process involving an enzyme and cells in the adrenal medulla, norepinephrine is turned into epinephrine. Epinephrine increases cardiac output and raises glucose levels in the blood. In the brain, surges of epinephrine can negatively affect memory. Epinephrine plays an important role in regulating arousal, reward and sensitivity to our environment.1421

Executive Function Executive function is a set of mental skills including working memory, mental flexibility and selfcontrol that help you get things done. These skills are controlled in the frontal lobe of your brain. They help you pay attention, manage time, switch focus, plan and organize, remember details, and avoid saying the wrong thing. When executive function isn’t working well, your behavior is less controlled. Executive function is often related to ADHD.

Fat Soluble There are two varieties of supplements; water soluble and fat soluble. Water soluble supplements like any of the B Vitamins and Vitamin C dissolve in water. And excess amounts are excreted through your kidneys if you have excess amounts in your system.

Fat soluble supplements including vitamins A, D, E, K and most of the racetams dissolve in fat. And are stored in fat in your body (your brain is 60% fat). For fat soluble nootropics to be more effective they need to be taken with some type of fat. Examples are a tablespoon of coconut or extra virgin olive oil. Unlike water soluble supplements which go directly into your bloodstream, fat-soluble nootropics are absorbed through your intestinal wall and into your lymph system. Once in your lymph system, the nootropics are sent to your bloodstream where they are available for use by your brain.

Focus Focus is the act of directing your total attention towards a specific task. Successful focus is achieved with a singular presence of mind when completing a task. Conversely, multi-tasking is not focus. Focus is simply the act of undergoing only one task.

Free Radicals Free radicals, reactive oxygen species and reactive nitrogen species are generated by your body by various natural systems, exposure to different natural chemical conditions or pathological states. A balance between free radicals and antioxidants to counteract them is necessary for healthy cell function. Free radicals cause problems for lipids, proteins and DNA and can trigger a number of human diseases. Antioxidants can assist in coping with this oxidative stress.

Glial Cells Glial cells or glia are distinct from neurons (nerve cells). Types of glial cells include astrocytes, ependymal cells, microglia, Schwann cells, and oligodendrocytes. And make up the white matter in your brain which accounts for about 90% of your brain cells. Astrocytes help provide nutrients to neurons. And oligodendrocytes help produce the myelin sheath coating protecting the axons protruding from neurons.

Glutamate Glutamate is a neurotransmitter that is responsible for sending signals between neurons in the brain. This plays an important role in learning and forming memories.

Gray Matter Gray matter in the brain is packed with billions of neurons. Because there are so many of them it’s tempting to think of neurons as very tiny. In reality, some neurons have axons (nerve fibers) that are very long. When many axons are grouped together, they appear as white matter. White matter is a collection of long, insulated axons which are the outgoing branches of neurons that connect various parts of the brain together.

The white color comes from myelin, which is the lipid, insulating material wrapped around those long axons.

Hippocampus The hippocampus is a small region of your brain associated with long-term memory and spatial navigation. In disease such as Alzheimer’s, the hippocampus is one of the first areas of the brain to become damaged. This leads to memory loss and disorientation.

Histamine Histamine is a type of biogenic amine neurotransmitter that is responsible for behavior like wakefulness and arousal. It also plays an important part in motivation and reward-oriented behavior. Histamine is essential in the acquisition and storage of short and long-term memory. When histamine signaling goes wrong in the brain it can lead to addictive behavior and degenerative diseases like Parkinson’s and multiple sclerosis.1422

Ion Channel An Ion Channel is a cell structure which lets ions enter or leave. Ion channels are sometimes associated with neuroreceptors which open or close a channel depending on the presence of a neurotransmitter.

Krebs Cycle Krebs Cycle is also known as the “citric acid cycle”, or tricarboxylic acid (TCA) cycle. This cycle is at the center of cellular respiration in your brain. And throughout the cells in your body. The Krebs cycle is a series of chemical reactions used to release stored energy through the oxidation of acetyl-CoA (which is derived from carbohydrates, fats and proteins). It releases this energy in the form of adenosine triphosphate (ATP). This metabolic pathway is derived from citric acid (tricarboxylic acid) that is consumed and regenerated by this sequence of events to complete the cycle. This cycle consumes acetate (acetyl-CoA) and water, and reduces NAD+ to NADH. Which produces carbon dioxide as a waste byproduct. The NADH generated by the Krebs cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients needed as chemical energy to form ATP. The primary source of fuel created within your brain cell’s mitochondria. You can maintain and boost the health of your cellular Krebs cycle by using the nootropics AlphaLipoic Acid, Choline Citrate, Ginseng, Magnesium, NADH and Vitamin B5 (Pantothenic Acid).

Long-Term Memory Long-Term Memory describes the type of memory associated with an event or information acquired by the mind long ago. These memories are often pieced together by the brain with inaccurate or imagined information. This

inaccurate memory storage can come from your perception of an event or thing, conditioning, or any other faulty input. Healthy, psychologically sound individuals have access to an impressive information storage system to draw from. On the other hand, unhealthy and psychologically messed-up people can also access this storage system. Both groups can boost access to this long-term memory with the use of certain Nootropics.

Long-Term Potentiation Long-Term Potentiation is the term used to describe a strengthening of synapses needed to create longterm memory. “Neurons that fire together, wire together”. Transcription factors such as cAMP responsive element binding protein (CREB), once a phosphate group is added, leads to gene expression. Which leads to changes in expression of proteins needed for producing and maintaining changes in synaptic strength. And long-term memory.

Mild Cognitive Impairment (MCI) Mild Cognitive Impairment is characterized by cognitive impairment outside of the expected decline caused by aging. Unchecked, MCI can eventually lead to dementia. Those suffering mild cognitive impairment begin to notice difficulty with memory and cognition. Amyloid Plaques & Neurofibrillary Tangles, poor blood flow, and strokes all contribute to MCI. There is no known single cause of mild cognitive impairment. MCI is likely caused by a combination of factors. And is often prevented or reversed through the use of nootropics.

MAOI Monoamine Oxidase Inhibitor (MAOI) is a substance which inhibits naturally occurring enzymes in your brain. This inhibition helps increase levels of neurotransmitters like serotonin and dopamine. Be cautious about using nootropics that boost neurotransmitters like serotonin or dopamine combined with MAOI’s. Too much serotonin or dopamine can cause serious problems in the brain including “serotonin syndrome”.

Mitochondria Mitochondria are organelles within each of your cells responsible for metabolizing or breaking down carbohydrates and fatty acids used to generate cellular energy. This cellular energy is in the form of a chemical molecule called adenosine triphosphate (ATP) which is generated within the mitochondria.

Myelin Myelin sheaths are a combination of proteins and phospholipids that form an insulating-like sheath around axons in your brain. And are what give your brain’s white matter its white color.

Myelin helps insulate and protect axons much like electrical tape wrapped around a bunch of wires. Myelin also assists optimal action potential (electrical signaling) through the axon. Insufficient or damaged myelin is linked to neurodegeneration and diseases such as Multiple Sclerosis. SAM-e, Vitamin B1 (Thiamine), Vitamin B6, Vitamin B9 (folate), and Vitamin B12 are critical for normal myelin formation.

Naturopath A Naturopath is a health care practitioner who uses natural systems of healing including the use of supplements instead of prescription drugs.

NDMA Receptors Similar to the AMPA receptor, the NMDA receptor is also paired with an ion channel. But this channel lets calcium ions rather than sodium ions into the neuron. When this cell is at resting potential, the calcium channel is blocked by magnesium ions (Mg2+), so that even if glutamate binds to the receptor, calcium cannot enter that neuron. For these magnesium ions to leave that channel, the neuron’s dendrites must be depolarized. This happens through the sustained action of the AMPA receptors. Once the magnesium leaves the NDMA receptors, large numbers of calcium ions enter that cell. This sets off several biochemical reactions that make this synapse more efficient for an extended period of time. This is called Long-Term Potentiation, and is associated with the plasticity that allows long-term memories to form.

Nerve Growth Factor Nerve Growth Factor (NGF) is a group of small biomolecules (neurotrophic factors) and small proteinlike molecules (neuropeptides) involved in the regulation of growth, maintenance, neurogenesis and survival of neurons.

Neurons Neurons are nerve cells in your brain. They function as conduits of information from one neuron to another neuron. This signaling between neurons are actually chemically-produced electrical signals. As the human brain ages, the production of new neurons begins to slow. Old neurons begin to die. And age-related disease begins to set in. Neurogenesis, or the birth of new neurons can be initiated with the use of certain nootropics.

Neurogenesis Neurogenesis is defined as the birth and growth of new neurons. The science on neurogenesis is fairly new but this much we know – neurogenesis plays a major role in learning, memory formation and

recall.

Neuroplasticity Neuroplasticity is the ability of your brain to change structure. This includes the internal structure of neurons, and an increase in the number synapses between neurons. Some evidence indicates that short-term memory depends on electrical and chemical events in the neurons rather than changes in structure. Long-term memory may be dependent on changes in brain structure including neurogenesis, and increases in synapses between neurons.

Neuroreceptor A neurotransmitter receptor, or neuroreceptor are typically proteins on the surface of cells that recognize and bind to specific neurotransmitters. Neuroreceptors allow cells to communicate with one another through chemical signaling. Once bound, the receptor can change shape, and cause a cascade of chemical events within the cell. These events can alter which genes are turned on or off and can make the cell more or less likely to release its own neurotransmitters. Each type of neurotransmitter can have multiple receptors each with a different role to play in the brain.

Neurotransmitter A Neurotransmitter is a broad term that refers to chemicals that act as communicators of information. Thus relaying signals in the brain to other parts of the brain. And throughout the body. To be considered a neurotransmitter, a molecule must; • • • •

be produced inside a neuron, found in the neuron’s terminal button, and released into the synaptic gap upon the arrival of an action potential. produce an effect on the postsynaptic neuron. after it has transmitted its signal to this neuron, it must be deactivated rapidly. have the same effect on the postsynaptic neuron when applied experimentally as it does when secreted by a presynaptic neuron.1423

Examples of neurotransmitters are acetylcholine, dopamine, GABA, glutamate, norepinephrine and serotonin.

Nootropic A nootropic is a substance capable of enhancing brain or mental function. Nootropics can help you boost memory, learning and overall brain function. The term “nootropic” is relatively new. Romanian psychologist and chemist Dr. Corneliu Giurgea synthesized Piracetam in 1963. And coined the term “nootropic” in 1972.1424 It is derived from the Greek nous (“mind”) and trepein (to bend).

Dr. Giurgea described a nootropic as having the characteristics of enhancing learning and memory. It should protect the brain while increasing natural cognitive processes. And should not be toxic, nor stimulate or depress the brain.

Nootropic Stack A nootropic stack refers to combining two or more nootropics to achieve a desired effect.

Noradrenaline Noradrenaline is another name for norepinephrine.

Norepinephrine Norepinephrine is a stress hormone. It affects parts of the brain where attention and responding actions are controlled. Along with epinephrine, norepinephrine underlies the fight-or-flight response. It increases heart rate, triggering the release of glucose from energy stores. And increases blood flow to skeletal muscle. Norepinephrine is synthesized from dopamine by dopamine β-hydroxylase. It is released from the adrenal medulla into the blood as a hormone. It is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons. The actions of norepinephrine are carried out by binding to adrenergic receptors.1425

OTC OTC = Over-the-counter means substances like supplements which are available in online or brick & mortar stores without a prescription.

Oxidative Stress Oxidative Stress often results from an imbalance between the production of free radical reactive oxygen species, and the antioxidants required to counteract them. Because your brain is the most energyintensive organ in your body, it also hosts high free radical activity. If left unchecked, these free radicals can damage and even destroy neurons. This oxidative stress is linked to a host of neurodegenerative diseases including Alzheimer’s and Parkinson’s Disease. Several nootropics have been shown to combat oxidative stress including Acetyl-L-Carnitine (ALCAR), Alpha-Lipoic Acid, Coenzyme Q10, Ginkgo biloba, Gotu kola, L-Carnosine, N-Acetyl L-Cysteine (NAC), Piperine, PQQ, Pterostilbene, Resveratrol, Rhodiola Rosea, St. John’s wort, and Vinpocetine.

Peptide A peptide is a compound consisting of two or more amino acids linked in a chain. All humans have peptides in their body. You could consider peptides one of the building blocks of life. When a peptide chain gets especially long, it turns into a protein. The amino acid chain of peptides is

called a covalent bond. A covalent bond occurs when atoms share electrons. This particular covalent bond is known as a peptide bond or amide bond. It forms when the carboxyl group of one amino acid attaches to another. Some peptides regulate hormones, while others can have an antibiotic function.

pH pH is a measure of acidity or alkalinity of a substance.

Phospholipids Phospholipids are a combination of lipids (fats) and phosphorus. Phosphatidylcholine (PC) and phosphatidylserine (PS) are the two most important phospholipids in the cells of your body. Your body cannot function normally without them. Phospholipids are also critical for optimal brain health. They assist brain cells in communicating. And influence how well neuroreceptors function. Phospholipids are found in many foods. But are in higher concentrations in soy, eggs and the brain tissue of animals. Taking supplemental phosphatidylcholine (PC) and phosphatidylserine (PS) can lead to improved memory and learning.

Potentiation Potentiation is the influence of a lesser active drug or substance on the effects realized from a drug already in your system.

Precursor A precursor is a compound that participates in a chemical reaction that produces another compound. In your body and brain, the term “precursor” refers to a chemical compound preceding another in a metabolic pathway.

Psychosis Psychosis is a person’s loss of ability to distinguish reality as perceived by others. It’s often seen as hallucinations, delusions and disturbances of thought and mood.

Racetams Racetams all stem from the original “nootropic” called piracetam. Both piracetam and nootropic were named by the inventor of piracetam, the Romanian psychologist and chemist Dr. Corneliu Giurgea. The most common racetams are Aniracetam, Piracetam, Pramiracetam, and Oxiracetam. They all share a 2-pyrrolidone nucleus made up of oxygen, nitrogen, and hydrogen. Racetams are known for boosting energy, focus, learning, memory and mood. Racetams can also help

increase neuroplasticity, making it easier to learn, absorb and memorize new concepts.

Recall Recall is one of the three major components of memory. The others are encoding and storage. Think of the human brain like an organic computer. Recall is the process of retrieving a memory that has been encoded and stored in the brain’s supercomputer.

Receptor A receptor is a structure on or inside a cell which receives a chemical signal.

Reuptake Reuptake is the process by which used neurotransmitters are taken back into cells to be recycled or destroyed.

Serotonin Serotonin is a neurotransmitter made from the amino acid tryptophan. The human body cannot make tryptophan so you must get it from the food you eat. Tryptophan is most abundant in meat and fowl. Once you eat food containing tryptophan, your digestion grabs the proteins in your gut. Which is transported by your blood to your brain. And then converted to serotonin. Serotonin is an inhibitory neurotransmitter which means it governs excessive stimulating hormones like dopamine from firing in the brain. Serotonin is present throughout the entire brain, from bottom to top. When you have adequate serotonin levels in your brain and it’s working properly, you’ll be confident, easy-going, flexible, happy, and positive. Serotonin deficiency can result in you becoming depressed, irritable, obsessive, negative and worried.

Serotonin Syndrome Serotonin Syndrome symptoms usually occur within several hours of taking a new drug or nootropic. Or increasing the dose of the drug or nootropic you’re already using. Symptoms can include agitation, confusion, rapid heart rate, dilated pupils, loss of muscle coordination, muscle rigidity, heavy sweating, diarrhea, headache, and shivering. Severe serotonin syndrome can be life-threatening. Signs include high fever, seizures, irregular heartbeat and unconsciousness. Caution is strongly advised when using any nootropic that boosts serotonin uptake in your brain. Especially when combining them with any drug or nootropic that is already boosting serotonin.

Short-term Memory Short-term Memory is also known as primary or active memory. It is characterized as being very brief (i.e. seconds), and is limited to what you can remember and retain for 20 to 30 seconds.

The human brain can only retain new information to a certain extant (chunk capacity) and only temporarily (temporal capacity). Short-term memory can be boosted using certain nootropics.

Stimulant A stimulant is any substance that increases activity in the central nervous system. Stimulants can cause wakefulness, alertness, and often feelings of well-being. An overdose of stimulants can cause anxiety, jitteriness, and insomnia. Examples of stimulants include the prescription drugs Adderall and Ritalin.

Sublingual Sublingual refers to taking a nootropic or other supplement by placing it under your tongue. Dissolving a substance under your tongue allows for better bioavailability because it’s absorbed directly into your bloodstream through the tissues in your mouth.

Synapses Synapses are the empty spaces between neurons (brain nerve cells). When neurons fire, they send electrical signals across the synaptic cleft to the neuron next door. Healthy brain activity is dependent on the proper function of synaptic activity. Obstructions like Amyloid Plaques can block synapses and cause serious problems with many brain functions including cognition, learning and memory.

Tolerance In pharmacology, tolerance describes the decrease or loss of effectiveness or response to a drug or nootropic. Typically, due to recent or prolonged exposure to that substance. Tolerance also includes the need for increasing doses of a drug or nootropic over time to maintain the same effect. Cycling is often used by nootropic users to counteract tolerance. An example of cycling is using a nootropic for 5 days, taking a 2-day break from using the nootropic and resuming use for another 5 days.

Upregulation Upregulation is a process in which the number or activity of receptors increases, typically in response to abnormally low activity.

White Matter See definition of Gray Matter to get an understanding of brain White Matter.

Uptake Uptake is the absorption by your body, and in the case of nootropics, by your brain, of a substance like a nootropic.

Working Memory Working memory is distinct from short and long-term memory. These are memories that are not only remembered, but simultaneously processed. You not only remember information that is important to you, you also remember the purpose of the information, and why you decided to remember it.

YMMV YMMV = Your Mileage May Vary is a term commonly used in the nootropic community. Meaning people experience reactions to certain nootropics very differently. Always remember that when someone describes their experience with a nootropic, you are unlikely to have the exact same experience.

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OceanofPDF.com

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Taurine

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Vitamin B8 (Inositol) 1295 Wiese T.J., Dunlap J.A., Conner C.E., Grzybowski J.A., Lowe W.L. Jr., Yorek M.A. “Osmotic regulation of Na-myo-inositol

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