Substance Abuse and Emotion [1 ed.] 1433805340, 9781433805349

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Substance Abuse and Emotion Edited by Jon D. Kassel

Substance Abuse and Emotion

Substance Abuse and Emotion Edited by Jon D. Kassel

AMERICAN

PSYCHOLOGICAL

WASHINGTON,

DC

ASSOCIATION

Copyright © 2010 by the American Psychological Association. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, including, but not limited to, the process of scanning and digitization, or stored in a database or retrieval system, without the prior written permission of the publisher. Published by American Psychological Association 750 First Street, NE Washington, DC 20002 www.apa.org

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In the U.K., Europe, Africa, and the Middle East, copies may be ordered from American Psychological Association 3 Henrietta Street Covent Garden, London WC2E 8LU England Typeset in Goudy by Circle Graphics, Columbia, MD Printer: Edwards Brothers, Inc., Ann Arbor, MI Cover Designer: Berg Design, Albany, NY Technical/Production Editor: Dan Brachtesende The opinions and statements published are the responsibility of the authors, and such opinions and statements do not necessarily represent the policies of the American Psychological Association.

Library of Congress Cataloging-in-Publication Data Substance abuse and emotion / edited by Jon D. Kassel.-1st ed. p.em.

Includes bibliographical references and index. ISBN-13: 978-1-4338-0534-9 ISBN-10: 1-4338-0534-0 1. Substance abuse. 2. Emotions. 3. Addicts-Psychology. 4. Compulsive behavior-Etiology. 5. Substance abuse-Etiology. l. Kassel, Jon D. RC564.S8265 2010 616.86--dc22 2009005548

British Library Cataloguing.in-Publication Data A CIP record is available from the British Library.

Printed in the United States of America First Edition

CONTENTS

Contributors ................................................................................................ ix Acknowledgments ....................................................................................... xi Introduction: The Complex Interplay Between Substance Abuse and Emotion.................................. .................................... 3 ] on D. Kassel and]ennifer C. Veilleux

I. Theoretical Perspectives ...................................................................... 13 Chapter 1.

Negative Reinforcement: Possible Clinical Implications of an Integrative ModeL.......................... 15 Danielle E. McCarthy, John]. Curtin, Megan E. Piper, and Timothy B. Baker

Chapter 2.

Positive Reinforcement Theories of Drug Use ............... 43

Harriet de Wit and Luan Phan

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Chapter 3.

Cognitive Theories of Drug Effects on Emotion ............ 61

Jon D. Kassel, Margaret C. Wardle, Adrienne}. Heinz, and Justin E. Greenstein Chapter 4.

Drug Craving and Affect............................ .................... 83

Stephen T. Tiffany Chapter 5.

Developmental Perspectives: Affect and Adolescent Substance Use ........................................... 109

Craig R. Colder, Laurie Chassin, Matthew R. Lee, and Ian K. Villalta Chapter 6.

Evolutionary Substrates of Addiction: The Neurochemistries of Pleasure Seeking and Social Bonding in the Mammalian Brain......................... ...... 13 7

Jaak Panksepp II. Advances in Assessment, Methodology, and Treatment ................ 169

Chapter 7.

Emotions and Relapse in Substance Use: Evidence for a Complex Interaction Among Psychological, Social, and Biological Processes ................................... 171

Katie Witkiewitz and Johnny Wu Chapter 8.

The Complexities of Modeling Mood-Drinking Relationships: Lessons Learned From Daily Process Research ........................................................... 189

Cynthia Mohr, Stephen Armeli, Howard Tennen, and Michael Todd Chapter 9.

Ecological Momentary Assessment of Mood-Smoking Relationships in Adolescent Smokers ................................................. 217

Robin Mermelstein, Donald Hedeker, and Sally Weinstein Chapter 10.

Cerebral Deficits Associated With Impaired Cognition and Regulation of Emotion in Methamphetamine Abuse............. .......................... 23 7

Andy C. Dean and Edythe D. London

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CONTENTS

Chapter 11.

Addiction and Emotion: Theories, Assessment Techniques, and Treatment Implications .................... 259

David H. Epstein, Jessica WiUner~Reid, and Kenzie L. Preston Afterword: New Frontiers in Substance Abuse and Emotion ................. 281

Jon D. Kassel and Daniel P. Evatt Index ........................................................................................................ 287 About the Editor ...................................................................................... 297

CONTENTS

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CONTRIBUTORS

Stephen Armeli, PhD, Department of Psychology, Fairleigh Dickinson University, Teaneck, NJ Timothy B. Baker, PhD, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison Laurie Chassin, PhD, Department of Psychology, Arizona State University, Tempe Craig R. Colder, PhD, Department of Psychology, State University of New York at Buffalo John J. Curtin, PhD, Department of Psychology, University of WisconsinMadison Andy C. Dean, PhD, Semel Institute, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles Harriet de Wit, PhD, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL David H. Epstein, PhD, National Institute on Drug Abuse, Baltimore, MD Daniel P. Evatt, PhD, Department of Psychology, University of Illinois at Chicago Justin E. Greenstein, PhD, Department of Psychology, University of Illinois at Chicago

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Donald Hedeker, PhD, Epidemiology and Biostatistics, Institute for Health Research and Policy, University of Illinois at Chicago Adrienne J. Heinz, MA, Department of Psychology, University of Illinois at Chicago Jon D. Kassell, PhD, Department of Psychology, University of Illinois at Chicago Matthew R. Lee, BS, Department of Psychology, Arizona State University, Tempe Edythe D. London, PhD, Semel Institute, Department of Psychiatry and Biobehavioral Sciences, Department of Molecular and Medical Pharmacology and the Brain Research Institute, University of California, Los Angeles Danielle E. McCarthy, PhD, Department of Psychology, Rutgers, The State University of New Jersey, Piscataway Robin Mermelstein, PhD, Psychology Department, Institute for Health Research and Policy, University of Illinois at Chicago Cynthia Mohr, PhD, Department of Psychology, Portland State University, Portland, OR Jaak Panksepp, PhD, College of Veterinary Medicine, Washington State University, Pullman Luan Phan, MD, Department of Psychiatry, University of Michigan, Ann Arbor Megan E. Piper, PhD, Center for Tobacco Research and Intervention, University of Wisconsin-Madison, School of Medicine and Public Health Kenzie L. Preston, PhD, National Institute on Drug Abuse, Baltimore, MD Howard Tennen, PhD, Department of Community Medicine and Health Care, University of Connecticut Health Center, Farmington Stephen T. Tiffany, PhD, Department of Psychology, University at Buffalo, The State University of New York, Buffalo Michael Todd, PhD, Prevention Research Center, Pacific Institute for Research and Evaluation, Berkeley, CA Jennifer C. Veilleux, MA, Department of Psychology, University of Illinois at Chicago Ian K. Villalta, BA, Department of Psychology, Arizona State University, Tempe Margaret C. Wardle, PhD, Department of Psychology, University of Illinois at Chicago Sally Weinstein, PhD, Department of Psychology, Institute for Health Research and Policy, University of Illinois at Chicago Jessica Wi1lner~Reid, BSc, National Institute on Drug Abuse, Baltimore, MD Katie Witkiewitz, PhD, Alcohol and Drug Abuse Institute, University of Washington, Seattle Johnny Wu, MA, Department of Psychology, University of Washington, Seattle x

CONTRIBUTORS

ACKNOWLEDGMENTS

Over the course of my life, I have been touched by the dire consequences of addiction and seen firsthand the emotional pain and suffering this disorder can inflict. Indeed, I believe that there are few among us who have not been witness to the psychological, physical, and spiritual damage wrought by the misuse of drugs. Acknowledging that the "causes" of substance abuse are many and varied, I have nonetheless come to believe that it is the relationship between drugs and emotion that ultimately emerges as the most critical in the context of understanding drug abuse etiology, maintenance, and relapse. As such, I dedicate this book to all who have personally suffered from addiction; to the clinicians who compassionately treat such individuals; and to those whose research has shed light on the reinforcing mechanisms underlying drug dependence, resulting in more effective prevention and intervention of this devastating disorder. Many individuals have served as formal and informal mentors, emotional guides, and close friends. These people have fueled my intellectual curiosity and provided support whenever I needed it in more profound ways than they will ever know: Saul Shiffman, Dorothy Hatsukami, Robin Mermelstein, Eric Wagner, Dennis McCaughan, and the Hazelden Foundation. I thank you alL

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I also want to express my sincere appreciation and thanks to the contributors to this volume, all of whom are leaders in the field who were more than willing to think outside the box; the supporters of my research program, the National Institute on Alcohol Abuse and Alcoholism and the National Cancer Institute; and the people at the American Psychological Association who coaxed me into taking on this challenge and provided support and encouragement throughout the entire process. Last, I want to especially express my love and gratitude to my wife, Rena, who has steadfastly stood by me during my relatively late-in-life odyssey through graduate school and academia-and everything else. I also thank my daughters, Melanie and Hayley, and my son, Joe-you are the lights of my life and provide the ultimate inspiration for my work. Finally, I dedicate this book to the memories of my sister, Barbara Kassel Brotman, and my parents, Ted and Estelle KasseL

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ACKNOWLEDGMENTS

Substance Abuse and Emotion

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INTRODUCTION: THE COMPLEX INTERPLAY BETWEEN SUBSTANCE ABUSE AND EMOTION JON D. KASSEL AND JENNIFER C. VEILLEUX

The pathways to substance abuse and dependence are, no doubt, complex, comprising cultural, peer, psychological, and biological influences (Kassel, Weinstein, Skitch, Veilleux, & Mermelstein, 2005). Yet one of the most pervasive beliefs in modem and even ancient societies is the idea that the use (and misuse) of drugs is often linked to both affective precipitants and consequences. Indeed, as Panksepp, Nocjar, Burgdorf, Panksepp, and Huber (2004) asked (and answered): "Would individuals exhibit addictive behaviors if there were no affective payoffs? We suspect an answer of 'no' for both humans and other species" (p. 93). With this opinion we wholeheartedly concur.

WHY STUDY SUBSTANCE ABUSE AND EMOTION? The notion that emotions (be they of a positive or negative nature) are inextricably linked to substance use and abuse is as old as the ages, permeating the very fabric of our society. Hence, it is commonly believed that individuals who abuse drugs do so out of hedonistic desires run amok or, conversely, out of a need to escape or assuage aversive states of negative affect. It is important to note that these ideas have not only been given voice by popular culture but also

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have been the subject of empirical scrutiny and theoretical debate for many years. By way of example, it has become almost axiomatic within the scientific field that, across multiple drugs of abuse, such drugs are self-administered, in great part, as a means of diminishing uncomfortable states of stress and negative affect. As such, the tenets underlying the self-medication (Khantzian, 1997), stress-coping (Wills & Shiffman, 1985), and tension-reduction models (Conger, 1956) of drug abuse have assumed the status of truisms, despite evidence that is, at best, equivocal. Contributing, in great part, to any confusion surrounding the complex associations between drug abuse and emotion is the realization that causal inferences are frequently derived from correlational, cross-sectional data. Thus, whereas it is abundantly clear that individuals who abuse substances are much more likely to manifest comorbidity (in the form of disorders often typified by affective distress, e.g., depression and anxiety, which we discuss shortly), such observations cannot speak to issues of causal mechanisms governing said comorbidity. Whereas these issues have been addressed in some detail previously (Kassel & Hankin, 2006; Kassel, Stroud, & Paronis, 2003), the bottom line is that only through sound, intensive laboratory and field studies can researchers begin to (a) determine the role played by emotion in promoting (cueing) drug use and (b) understand the effect of drugs on emotional systems. Defining relevant constructs is also certainly integral to examining drug-emotion relationships. Generally speaking, many theorists (although by no means all) draw distinctions between the concepts of affect, emotion, and mood. Affect is generally perceived to be a superordinate category defined by valenced (positive or negative) feelings (Ortony & Turner, 1990; Russell, 2003). Affect is evaluative, signaling something either about the properties of an eliciting stimulus or about the individual's internal resources (Larsen, 2000; Morris, 2000), and encompasses the phenomena of mood and emotion (Clore & Ortony, 2000; Forgas, 1995). Mood is typically defined as a less intense, longer lasting affective state not attributable to a particular object or event (Forgas, 1995; Russell, 2003). Moods may exist outside conscious awareness but may also be consciously perceived (Morris, 2000). By contrast, emotions are typically defined as discrete, short-lived feelings prompted by particular causes and associated with specific objects (Forgas, 1995; Russell, 2003). Another critical approach to delineating the relationship between drug abuse and emotion can be realized through sound theory building and testing. Indeed, although drug abuse continues to exact a devastating toll on society, in recent years tremendous advances have been made on numerous theoretical fronts in an effort to better grasp the mechanisms governing these destructive behaviors. Toward this end, this edited volume brings together some of the foremost experts who conduct groundbreaking research that examines the theoretical bases of the links between substance abuse and emotion. It is our

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hope that this volume will offer a comprehensive review and integration of the theoretical and empirical literature in this rapidly expanding field. Correspondingly, it is important to note that tremendous advances have been made within the realm of emotion and affective science as well (e.g., Davidson, Scherer, & Goldsmith, 2003; Panksepp, 1998). Hence, progress within cognitive and affective neuroscience, for example, has been rapid in recent years, offering new and exciting insights into the experience of emotion as well as its physiological bases. Transdisciplinary approaches to the study of emotion-and, indeed, to the study of drug abuse-have also flourished, adding to a burgeoning theoretical and empirical base on which to further study and question our enduring (if at times questionable) beliefs regarding the motivational underpinnings of drug abuse and dependence. Before we proceed any further, however, we would like to provide a brief overview of the comorbidity between substance use and disorders of affective distress, because we believe that it is this database that ultimately sets the stage for inquiry into how, for whom, and in which contexts drugs may influence emotion and, conversely, emotions may influence drug use.

A REFLECTION ON COMORBIDITY It is well established that substance use disorders frequently present themselves in conjunction with other psychiatric conditions (Compton, Thomas, Stinson, & Grant, 2007; Grant et aL, 2004; Kessler, 2004; Merikangas et aL, 1998). Substance use occurs more often alongside externalizing disorders (Le., antisocial personality disorder) relative to disorders of affect (e.g., depression and anxiety; Compton et al., 2007; Kessler, 2004). At the same time, however, it is important to note that rates of anxiety and depression (at the level of both clinical and subclinical presentation) are far greater in substance users compared with the general population (e.g., Lasser et al., 2000). The fact that a relationship exists between substance use and emotional disorders is clear, but the nature of the relationship is far from well understood. For instance, the association between emotion and drug use appears to change over time such that rates of comorbidity are far higher for drug and alcohol dependence than for abuse (Conway, Compton, Stinson, & Grant, 2006; Grant et al., 2004). Correspondingly, the prevalence of anxiety and depression is significantly higher among substance abusers relative to individuals who use, but do not abuse, drugs and alcohol (Merikangas et al., 1998). On the face of it, then, these findings are not particularly surprising; after all, substance abuse and dependence are associated with greater frequency of use and increased functional impairment relative to sporadic users or even low-frequency regular users (American Psychiatric Association, 2000).

INTRODUCTION

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One of the central questions that inevitably arises from comorbidity research is that of causal influence: Do mental disorders predispose an individual to (cause) substance problems, or does substance use induce a vulnerability to (cause) emotional disorders? (Or are observed relationships between drug use and emotional distress attributable to third-variable influences?) To address these important questions, burgeoning research has attempted to distinguish between independent and substance-induced psychiatric conditions (e.g. Herrero, Domingo-Salvany, Torrens, Brugal, & The ITINERE Investigators, 2007; Ramsey, Kahler, Read, Stuart, & Brown, 2004), each of which appears to manifest unique symptomatic courses and is likely associated with different treatment concerns (Schuckit, 2006). Whereas epidemiological studies have typically found that the age of onset for anxiety and mood disorders predates that of substance abuse and dependence (Kessler, 2004), investigations attempting to disentangle causal pathways have yielded mixed findings. Some reveal that drug use predicts mood (Brook, Brook, Zhang, Cohen, & Whiteman, 2002; Merikangas et al., 1998; van Laar, van Dorsselaer, Monshouwer, & de Graaf, 2007; Wu & Howard, 2007) and anxiety (Kandel et al., 1997) disorders; however, many studies point to the opposite temporal pattern, such that anxiety and depression predate substance use issues (Kessler, 2004; Merikangaset al., 2004; Wittchen et al., 2007). Finally, some studies suggest no predictive relationship at all (e.g., Degenhardt, Coffey, Carlin, Moran, & Patton, 2007). Because specific types and classes of drugs exert unique effects on the brain and body, including differential effects on systems intimately related to emotional processing (Koob et al., 2004), it follows that the relationship between drug use disorders and psychiatric conditions might vary both by specific drug class and by specific mental disorder. For example, Merikangas and colleagues (1998) found that although mood disorders occurred subsequent to substance initiation, anxiety disorders preceded alcohol and drug problems. Rates of co-occurrence also appear to differ by drug class and mental disorder. Comorbidity rates typically are higher in mood disorders relative to anxiety disorders (Conway et al., 2006; Hasin, Stinson, Ogburn, & Grant, 2007) and higher for drugs with lower overall prevalence rates, such as inhalants (Wu & Howard, 2007) and tranquilizer/sedative use (Conway et al., 2006), compared with alcohol and more commonly used drugs, such as cannabis (Conway et al., 2006; Wittchen et al., 2007). Such observations suggest that people who become involved with less frequently used drugs-drugs that prompt less societal sanction-also experience more problematic mood and anxiety symptoms. Even within the same drug class, the method of self-administration may be associated with, and predict, differential affective outcomes. For instance, crack cocaine users tend to manifest higher levels of internalizing problems than cocaine powder users (Herrero et al., 2007).

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The waters are further muddied (yet, we hope, clarified somewhat) by consideration of moderator variables. For instance, numerous studies have revealed that the relationship between emotional disorders and substance use problems is stronger for women than men (Conway et al., 2006; Federman, Costello, Angold, Farmer, & Erkanli, 1997; Lubman, Allen, Rogers, Cementon, & Bonomo, 2007; Wu & Howard, 2007) and that comorbidity rates frequently differ by country and ethnicity (Federman et al., 1997; Merikangas et al., 1998). Methodological differences likely account for further variability in observed relationships across studies, because some investigations draw on nationally representative samples (e.g. Grant et al., 2004; Merikangas et al., 1998), whereas others focus on treatment-seeking or clinical samples (e.g. Herrero et al., 2007; Lubman et al., 2007). Also, many studies fail to control for coexisting mood and anxiety disorders (Kessler, 2004), or demographic characteristics, such as race or income (Hasin et al., 2007). Several recent investigations based on data from the National Epidemiologic Survey on Alcohol and Related Conditions from 2001 to 2002 have examined the comorbidity between substance use and psychiatric conditions after controlling for sociodemographic factors and concurrent relationships among mental disorders (Compton et al., 2007; Hasin et al., 2007).lt is important that, after controlling for psychiatric comorbidity, substance dependence was still associated with generalized anxiety disorder, major depression, and bipolar disorder, whereas relationships between substance abuse and depression and anxiety did not hold. So, when all is said and done, what does the literature on comorbidity really reveal? Well, we know that people who experience heightened levels of affective distress are more likely to use and abuse drugs. Burgeoning evidence also supports the reciprocal relationship: People who abuse drugs are more likely to experience disorders of affect. We view these findings as important for several reasons. First, they point to the obvious (but frequently overlooked) fact that substance abuse is almost always accompanied by emotional pain; that is-and counter to the notion entertained earlier that addiction may simply reflect uncontrolled hedonistic desire-individuals who abuse drugs are most often depressed, or anxious, or manifesting any number of symptoms of affective distress. Also, although our brief review of the literature focused primarily on full-blown disorders of affect, the association between substance abuse and emotional distress is witnessed in the presence of subclinical affective symptomatology as well (e.g., Kassel et aL, 2003). Nevertheless, one critical point that needs to be made in the context of this discussion is that the vast majority of such epidemiological findings are based on a between-persons level of analyses. As a result, we really know relatively little about how drug-affect relationships play out at the level of the individual (see Kassel et aL, 2003, 2006, 2010). In this light, we refer to

INTRODUCTION

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Borsboom, Mellenbergh, and van Heerden (2003), who argued that "to substantiate intraindividual causal conclusions, one must explicitly represent individual level processes in the measurement model" (p. 203). Although we do not believe that the "field" of substance abuse--disparate and fragmented though it may be-has done a particularly good job thinking about, yet alone measuring, such intraindividual processes as they relate to drug abuse and emotion, progress is being made in this respect (see, e.g., Cervone, Orom, Artistico, Shadel, & Kassel, 2007). Indeed, several of the chapters in this volume go some way toward addressing these concerns.

ORGANIZATION OF THIS BOOK AND ITS RELEVANT READERSHIP The next segment of the volume that awaits, Part I, is devoted to theoretical perspectives on substance abuse and emotion. Represented in this section are thoughts shared by leaders in the field, thoughts that are sure to provoke discussion, even debate. This theoretical coverage includes consideration of negative reinforcement theories (chap. 1), the role played by positive reinforcement mechanisms (chap. 2), the extent to which drug effects on emotion are cognitively mediated (chap. 3), the relationship between craving and emotion (chap. 4), developmental perspectives (chap. 5), and an ethological approach to the question of drug-emotion associations (chap. 6). Chapters in the next section, Part II, consider recent advances in assessment, methodology, and treatment. Topics covered include an examination of the role played by emotions in relapse to alcohol using novel statistical approaches (chap. 7), use of daily process methodology to assess mood-drinking relationships (chap. 8), ecological momentary assessment as a tool through which drug-emotion associations can be discerned at the level of the individual (chap. 9), the implementation of neuropsychological and neuroscience approaches toward assessing impaired cognition and mood in methamphetamine abusers (chap. 10), and how furthering our understanding of drug-emotion relationships holds important implications for substance abuse treatment (chap. 11). The volume concludes with an Afterword that discusses our thoughts about what the totality of our inquiry into substance abuse and emotion has revealed and where the field might go from here. All of this being said, we offer one caveat up front. Virtually every chapter in this volume could be expanded to form a book itself. Thus, although the coverage of the topic of substance abuse and emotion is extensive, it is ultimately far from complete. Correspondingly, whereas we aspired to cover as much of the relevant landscape as possible, some topics worthy of discussion probably received relative short shrift (although all are given

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at least some attention across chapters, e.g., behavior-genetics, the role played by personality, drug-emotion associations in older populations, psychophysiology as an assessment tool). With these limitations acknowledged, it is our hope that this edited volume will hold broad appeal to researchers and clinicians alike. Hence, professors and graduate students in addiction science, clinical psychology, and developmental psychopathology, as well as child and adult psychopathology, psychiatry, clinical social work, behavioral pharmacology, and behavioral neuroscience, represent but a few of the disciplines for whom this work should prove relevant. In addition to academic professionals, this volume is likely to appeal to a diverse array of clinicians (psychologists, social workers, and psychiatrists) because the chapters are focused on vulnerabilities to, and consequences of, substance abuse, in particular with respect to the role played by emotion. Moreover, the exemplary chapter on treatment implications (chap. 11) should prove invaluable to clinicians actually working with this difficult population. Indeed, virtually all of the chapters in this volume either implicitly or explicitly address treatment implications. Last, we encourage readers to approach this book as they would a novel. We believe that reading it from start to finish will provide a gestalt not afforded by any single chapter alone (although each and every chapter is certainly worthy in its own right). So, view the "consumption" of this book as a journey-one that will, we hope, enlighten and give rise to more questions that professionals in the field of substance abuse and emotion might be just a little better positioned to answer as a result of having read this volume.

REFERENCES American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC; Author. Borsboom, D., Mellenbergh, G. ]., & van Heerden,]. (2003). The theoretical status of latent variables. Psychological Review, 110, 203-219. Brook, D. W., Brook,]. S., Zhang, c., Cohen, P., & Whiteman, M. (2002). Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders. Archives of General Psychiatry, 59, 1039-1044. Cervone, D., Orom, H., Artistico, A., Shadel, W. G., & Kassel,]. D. (2007). Using a knowledge-and-appraisal model of personality architecture to understand consistency and variability in smokers' self-efficacy appraisals in high-risk situations. Psychology of Addictive Behaviors, 21,44-54. Clore, G. L., & Ortony, A. (2000). Cognition in emotion: Always, sometimes, or never? In R. D. Lane & L. Nadel (Eds.), Cognitive neuroscience of emotion (pp. 24--61). New York: Oxford University Press.

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Compton, W. M., Thomas, Y. F., Stinson, F. S., & Grant, B. F. (2007). Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States. Archives of General Psychiatry, 64, 566-578. Conger, J. J. (1956). Reinforcement theory and the dynamics of alcoholism. Quarterly Journal of Stwlies on Alcohol, 17, 296-305. Conway, K. P., Compton, W., Stinson, F. S., & Grant, B. F. (2006). Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions.Journal of Clinical Psychiatry, 67,247-257. Davidson, R. J., Scherer, K. R., & Goldsmith, H. H. (Eds.). (2003). Handbook of affective sciences. New York: Oxford University Press. Degenhardt, L., Coffey, c., Carlin, J. B., Moran, P., & Patton, G. C. (2007). Who are the new amphetamine users? A lO-year prospective study of young Australians. Addiction, 102, 1269-1279. Federman, E. B., Costello, E. J., Angold, A, Farmer, E. M. Z., & Erkanli, A (1997). Development of substance use and psychiatric comorbidity in an epidemiologic study of White and American Indian young adolescents the Great Smoky Mountains Study. Drug and Alcohol Dependence, 44, 69-78. Forgas, J. P. (1995). Mood and judgment: The affect infusion model (AIM). Psychological Bulletin, 117, 39-66. Grant, B. F., Stinson, F. S., Dawson, D. A., Chou, P., Dufour, M. c., Compton, W., et al. (2004). Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders. Archives of General Psychiatry, 61 , 807-816. Hasin, D. S., Stinson, F. S., Ogburn, E., & Grant, B. F. (2007). Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States. Archives of General Psychiatry, 64, 830-842. Herrero, M. J., Domingo-Salvany, A, Torrens, M., Brugal, M. T., & The ITINERE Investigators. (2007). Psychiatric co morbidity in young cocaine users: Induced versus independent disorders. Addiction, 103, 284-293. Kandel, D. B., Johnson, J. G., Bird, H. R., Canino, G., Goodman, S. H., Lahey, B. B., et al. (1997). Psychiatric disorders associated with substance use among children and adolescents: Findings from the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Journal of Abnormal Child Psychology, 25,121-132. Kassel, J. D., & Hankin, B. L. (2006). Smoking and depression. In A Steptoe (Ed.), Depression and physical illness (pp. 321-347). Cambridge, England: Cambridge University Press. Kassel,J. D., Hussong, A M., Wardle, M. c., Veilleux,J. c., Heinz, A J., Greenstein, J. E., et al. (2010). Affective influences in drug use etiology. In L. M. Scheier (Ed.), Handbook of drug use etiology: Theory, method, and empirical findings (pp. 183-206). Washington, DC: American Psychological Association. Kassel, J. D., Stroud, L. R., & Paronis, C. A (2003). Smoking, stress, and negative affect: Correlation, causation, and context across stages of smoking. Psychological Bulletin, 129, 270-304.

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Kassel, J. D., Veilleux, J. c., Wardle, M. c., Yates, M. c., Greenstein, J. E., Evatt, D. P., & Roesch, L. L. (2006). Negative affect and addiction. In M. al'Absi (Ed.), Stress and addiction: Biological and psychological mechanisms (pp. 171-190). New York: Elsevier. Kassel, J. D., Weinstein, S., Skitch, S. A., Veilleux, J., & Mermelstein, R. (2005). The development of substance abuse in adolescence. In B. L. Hankin & J. R. Abela (Eds.), Development of psychopathology: A vulnerability-stress perspective (pp. 355-384). Thousand Oaks, CA: Sage. Khantzian, E. J. (1997). The self-medication hypothesis of substance use disorders: A reconsideration and recent applications. Harvard Review of Psychiatry, 4, 231-244. Kessler, R. C. (2004). The epidemiology of dual diagnosis. Biological Psychiatry, 56, 730-737. Koob, G. F., Ahmen, S. H., Boutrel, B., Chen, S. A., Kenny, P. J., Markou, A., et a1. (2004). Neurobiological mechanisms in the transition from drug use to drug dependence. Neuroscience & Biobehavioral Reviews, 27, 739-749. Larsen, R. J. (2000). Toward a science of mood regulation. Psychological Inquiry, 11, 129-14l. Lasser, K., Boyd, J. W., Woolhandler, S., Himmelstein, D. u., McCormick, D., & Bor, D. H. (2000). Smoking and mental illness: A population-based prevalence study.JAMA, 284, 2606-2610. Lubman, 0.1., Allen, N. B., Rogers, N., Cementon, E., & Bonomo, Y. (2007). The impact of co-occurring mood and anxiety disorders among substance-abusing youth. Journal of Affective Disorders, 103, 105-112. Merikangas, K. R., Mehta, R. L., Molnar, B. E., Walters, E. E., Swendsen, J. D., Aguilar-Gaziola, S., et a1. (1998). Comorbidity of substance use disorders with mood and anxiety disorders: Results of the International Consortium in Psychiatric Epidemiology. Addictive Behaviors, 23, 893-907. Morris, W. N. (2000). Some thoughts about mood and its regulation. Psychological Inquiry, 11, 200-202. Ortony, A., & Turner, T.]. (1990). What's basic about basic emotions? Psychological Review, 97, 315-331. Panksepp, J. (1998). Affective neuroscience: The foundations of human and animal emotions. New York: Oxford University Press. Panskepp, J., Nocjar, c., Burgdorf, J., Panskepp, J. B., & Huber, R. (2004). The role of emotional systems in addiction: A neuroethological perspective. In R. A. Bevins & M. T. Bardo (Eds.), Nebraska Symposium on Motivation: Vol. 50. Motivational factors in the etiology of drug abuse (pp. 85-126). Lincoln: University of Nebraska Press. Ramsey, S. E., Kahler, C. W., Read, J. P., Stuart, G. L., & Brown, R. A. (2004). Discriminating between substance-induced and independent depressive episodes in alcohol dependent patients. Journal of Studies on Alcohol, 65,672-676. Russell, J. A. (2003). Core affect and the psychological construction of emotion. Psy-

chological Review, 110, 145-172.

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Schuckit, M. A (2006). Comorbidity between substance use disorders and psychiatric conditions. Addiction, 101, 76-88. van Laar, M., van Dorsselaer, S., Monshouwer, K., & de Graaf, R. (2007). Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population? Addiction, 102, 1251-1260. Wills, T. A, & Shiffman, S. (1985). Coping and substance use: A conceptual framework. In S. Shiffman & T. A. Wills (Eds.), Coping and substance use (pp. 3-24). New York: Academic Press. Wittchen, H., Frohlich, c., Behrendt, S., Gunther, A, Rehm, )., Zimmermann, P., et al. (2007). Cannabis use and cannabis use disorders and their relationship to mental disorders: A 10-year prospective-longitudinal community study in adolescents. Drug and Alcohol Dependence, 88S, S60-S70. Wu, L., & Howard, M. O. (2007). Psychiatric disorders in inhalant users: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug and Alcohol Dependence, 88, 146-155.

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I THEORETICAL PERSPECTIVES

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1 NEGATIVE REINFORCEMENT: POSSIBLE CLINICAL IMPLICATIONS OF AN INTEGRATIVE MODEL DANIELLE E. McCARTHY, JOHN J. CURTIN, MEGAN E. PIPER, AND TIMOTHY B. BAKER

Many addicted individuals report that they crave and use drugs to escape various forms of distress (e.g., Holahan, Moos, Hyolahan, Cronkite, & Randall, 2001); however, the hypothesis that people take drugs to alleviate distress is controversial because evidence does not consistently show that distress predicts drug use (Jaffe, 1992; Lyvers, 1998; van Ree, Gerrits, & Vanderschuren, 1999). In this chapter, we briefly review the history of models that assert that negative reinforcement learning (i.e., learning that drug self-administration is followed by a reduction in an aversive stimulus) plays a central role in addiction. We then summarize the current support for a reformulated negative reinforcement model of drug motivation (Baker, Piper, McCarthy, Majeskie, & Fiore, 2004) that specifies the conditions in which the distress that prods drug craving and self-administration will enter awareness and thus be amenable to both self-report and cognitive control (Curtin, McCarthy, Piper, & Baker, 2006). This model may explain the inconsistency in the observed relations between distress on the one hand, and indexes of drug motivation (urge report and self-administration) on the other hand. We conclude the chapter with a discussion of clinical implications of the reformulated model.

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A BRIEF HISTORY OF NEGATIVE REINFORCEMENT MODELS OF DRUG MOTIVATION Negative reinforcement learning has been proposed as an explanation for addictive drug use for at least the past half-century (Wikler, 1948). In operant conditioning, a behavior that is negatively reinforced by relief from a noxious stimulus is likely to be repeated in the future when the noxious stimulus is present. Escape from aversive drug withdrawal effects is thought to be a central motive for continued drug use due to repeated cycles oflearning that drug use alleviates aversive withdrawal symptoms. Withdrawal symptoms vary across drugs of abuse, but they have in common a core of negative affect symptoms, such as irritability, anxiety, and depressed mood (Gawin & Kleber, 1986; Hughes & Hatsukami, 1986; Kosman & Unna, 1968; Mansky, 1978). Recognition of this common core of distress has helped clarify the basis of the addictive liability of substances such as nicotine that do not lead to dramatic physical signs of withdrawal. Withdrawal symptoms develop rapidly following repeated use of drugs (Schulteis, Heyser, & Koob, 1997), so negative reinforcement learning may playa role early in an individual's drug use career as well as later, when dramatic withdrawal symptoms emerge. The view that relief of negative affect constitutes the core of negative reinforcement suggests that any sort of affective distress may cue drug use for the addicted individual, even if it does not arise from drug withdrawal (see Kassel, Stroud, & Paronis, 2003). Evidence indicates that the acute phase of withdrawal (2-7 days after discontinuation of drug use) is indeed a time of high relapse vulnerability (e.g., Kenford et al., 1994). Relapses sometimes occur long after withdrawal seems to have resolved (Brandon, Lazev, &}uliano, 1998), however, which would seem to challenge withdrawal relief as a primary motive for relapse. Wikler (1965) accounted for this by arguing that drug withdrawal responses, just like direct drug effects, can be conditioned through associative learning. Consistent with this claim, both the physical and affective symptoms of withdrawal can be reinstated by exposure to conditioned stimuli (e.g., Kenny & Markou, 2005; Mucha, 1987; O'Brien, 1976; Siegel, 1977). For example, recent research in rats demonstrated that cues (a light + tone compound) previously paired with naloxone-precipitated withdrawal elicited increased heroin consumption and decreased activity in reward pathways when presented without naloxone (Kenny, Chen, Kitamura, Markou, & Koob, 2006). Addiction models have identified negative reinforcement as a potent influence on drug use while recognizing the positive reinforcement also provided by drugs. The opponent process model of addiction, for instance, posits that drugs disturb homeostasis in a positive direction initially (the hedonically positive direct drug effect is called the a process), but this disturbance is followed by a countervailing response (called the b process) that returns the

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user to homeostatic balance (Solomon, 1977; Solomon & Corbit, 1973). With repeated drug use, the b process increases in amplitude and duration so that it overwhelms the initial appetitive a process, and the net effect of using drugs is a negative disturbance, which manifests as withdrawal symptoms. The opponent process model incorporates both positive and negative reinforcement learning and accounts well for the development of the tolerance and withdrawal that are hallmarks of addiction. Recently, Koob and Le Moal ( 1997, 2001) have extended the opponent process model. They asserted that addiction cannot be fully accounted for by homeostatic processes because addiction is an allostatic state in which the homeostatic reward set point is itself changed by drug use. They also asserted that repeated drug use disturbs the brain's reward system set point. This change in set point places an allostatic load on the individual, and dysregulation in the reward system leads to a "spiraling distress of addiction" (Koob & LeMoal, 2001, p. 111) in which stress systems are activated and reward systems are underactivated in abstinence. In essence, addicted individuals are changed by drug use so that they experience more stress and respond less to rewards when they are abstinent, which sets the stage for negative reinforcement by drug use. The allostatic reward model is grounded in animal research and evidence regarding the effects of drugs on reward, stress, and corticothalamic brain functions (Koob & LeMoal, 2001). Considerable evidence supports the core predictions made by these models of drug motivation. In particular, there is consistent, compelling evidence that drug use leads to aversive symptoms, primarily affective distress, when blood drug levels fall, even after a single exposure (e.g., Bickel, Stitzer, Liebson, & Bigelow, 1988; Heischman, Stitzer, Bigelow, & Liebson, 1989; Schulte is et al., 1997). According to negative reinforcement models, such distress is the setting event for negative reinforcement following readministration of drugs. Substantial evidence also supports the prediction that withdrawal distress predicts continued or renewed drug use (Baker, Piper, et al., 2004; Piasecki, }orenby, Smith, Fiore, & Baker, 2003; Sofuoglu, Dudish-Poulsen, Poling, Mooney, & Hatsukami, 2005). Withdrawal is not always a predictor of use, however, and failures to detect such relations (e.g., Patten & Martin, 1996) have been cited as evidence that negative reinforcement is not a primary motivation for addicted drug use (e.g., van Ree et al., 1999). In addition, self-reported drug motivation, in the form of cravings or urges, is not consistently higher during withdrawal than during or immediately after use (e.g., Fischman, Foltin, Nestadt, & Pearlson, 1990). Alternative models of drug motivation have been proposed to account for these inconsistencies. For example, Robinson and Berridge (1993, 2003) have proposed that drug motivation is characterized by sensitization of drugwanting even as drug-liking diminishes (Le., even when drug use is no longer reinforcing). Their incentive sensitization model has generated much interest

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and research (e.g., Bradberry & Rubino, 2006; Heinz et al., 2007) that supports the sensitization of incentive salience over repeated drug exposures (e.g., Mogg, Bradley, Field, & De Houwer, 2003; Taylor & Horger, 1999). The mixed evidence regarding the role of withdrawal symptoms in motivating continued or renewed drug use seems to invalidate the central tenets of negative reinforcement models of addiction. Any contemporary negative reinforcement model of drug motivation must account for the following observations: (a) Withdrawal symptoms are only sometimes predictive of drug use; (b) self-reported urges to use drugs are sometimes greater when withdrawal symptoms should be negligible or absent; (c) drug use following abstinence or stress does not consistently reduce distress; and (d) relapse sometimes occurs in the context of positive affect or euthymia, rather than distress.

THE REFORMULATED NEGATIVE REINFORCEMENT MODEL OF DRUG MOTIVATION In 2004, Baker et al. proposed a reformulated negative reinforcement model of drug motivation that attempts to account for the inconsistencies in past research and makes novel, testable predictions about the conditions in which withdrawal distress will predict urges to use and self-administration of drugs, two principal indicators of drug motivation (Baker, Piper, et al., 2004). The reformulation adds three stipulations to traditional concepts of negative reinforcement. First, the reformulated model specifies that the primary motive for drug use is avoidance or escape from affective (rather than somatic) components of withdrawal (e.g., Khantzian, 1997; see Figure 1.1). This prediction is based on the extensive research on the nature of withdrawal that suggests that affective distress is the common core in withdrawal across substances of abuse (e.g., Kosman & Unna, 1968; Mansky, 1978; Welsch et al., 1999). In addition, research suggests that affective symptoms have greater motivational significance than do somatic symptoms and that affective symptoms are particularly predictive of drug use (e.g., Kenford et al., 2002; McAuliffe, 1982). Basic research on emotion also highlights the priority afforded to affective information in information processing and the motivational correlates and consequences of affective states (Ohman, Dimberg, & Esteves, 1989; Sutton & Davidson, 1997). The explicit focus on affective withdrawal distress as the setting event for drug use in this model can account for past failures to reveal a link between undifferentiated withdrawal composites and drug use. Second, the reformulated model proposes that much drug motivational processing occurs outside of awareness (Baker, Brandon, & Chassin, 2004; Baker, Piper, et al., 2004); that is, although addicted individuals are usually aware that they are using drugs (but see Tiffany, 1990, and chap. 4, this volume), they are typically unaware of the motivational and decision-making

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Stressor

Falling Drug Blood Levels & Associated Cues

\ Affective Distress

Drug Use Motivation

Drug SelfAdministration

/

Provocative Novel or Incentive Cues

~//

Nonuse Motivation

Recruitment of Cognitive Control

/

Surprising Outcome

Alternative Behavior

Conscious Urge to Use

Figure 1.1. Integrated negative reinforcement model of drug motivation and boundary conditions of urges. Because of negative reinforcement learning, both withdrawal and exogenous stressors increase drug motivation that sometimes leads to drug self-administration and recruitment of cognitive control under certain circumstances, including the presence of provocative cues, and motivation to engage in a response other than drug use, disappointing or surprising outcomes. Non-drug use motivation moderates the effect of motivation to use drugs on cognitive control recruitment, such that recruitment of cognitive control is likely when both drug use and non-drug use motivation are strong, but not when only one response option is activated. Activation of cognitive control is reciprocally linked to conscious awareness of urges to use drugs, such that conscious urges are more likely when anterior cognitive control systems are engaged and cognitive control activity is sustained by the addicted individual's desire to resolve urges.

processes that prompt use (see Figure 1.1). We posit that experiencing repeated cycles of withdrawal relieved by substance use leads to automatization of drug-seeking routines in the context of withdrawal. With greater experience, individuals learn to detect earlier and more subtle signs of withdrawal symptoms that begin to emerge as soon as blood drug levels begin to fall. With enough practice, symptom detection becomes an automatic, preconscious process of anticipation of distress to come, which then spurs avoidance behavior (i.e., drug ingestion) to prevent symptom exacerbation. Thus, a welltrained user may self-administer drugs before he or she even consciously detects the distress that implicitly motivated the behavior. In this sense, drug use has much in common with other well-practiced responses in that strong stimulus-response (S-R) mapping results in relatively automatic execution of the primed response (Cohen, Dunbar, & McClelland, 1990; Curtin et al., 2006; Palfai, 2006).

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A substantial body of research indicates that implicit cognitive processes influence goal-directed behavior (e.g., Bargh, Gollwitzer, Lee-Chai, Bardollar, & Roman, 2001). In addition, basic research demonstrates that internal states can serve as conditioned stimuli for other internal states through interoceptive conditioning (Razran, 1961). As such, basic research supports the suggestion that motivational and self-monitoring (e.g., detection of interoceptive changes) processes can be automatized and performed outside of awareness. The prediction that much, if not most, drug motivational processing occurs outside of awareness allows the reformulated negative reinforcement model to account for the inconsistent relationship between self-reported distress and drug motivation (indexed by urges and use) reported in the human addiction literature. Third, the reformulated model articulates the way in which negative reinforcement learning, based on withdrawal-relief, generalizes to aversive affective states unrelated to withdrawal. Although it is not clear that all drug use reverses stress due to causes other than falling drug levels (Kassel et al., 2003), it is clear that many addicted individuals expect drug ingestion to help them relax and reverse distress triggered by stressors (e.g., Brandon, Juliano, & Copeland, 1999; Galen & Henderson, 1999). Stress is a potent trigger for renewal of drug self-administration among humans and animals (Kassel et al., 2003; Piazza & Le Moat, 1998; Shaham, Erb, & Stewart, 2000). The reformulated negative reinforcement model asserts that this relation reflects generalization of the learning regarding withdrawal-induced distress to nonpharmacologic distress that yields similar interoceptive stimuli (see Figure 1.1); that is, we propose that addicted individuals use drugs to escape distress, whether the distress is due to drug deprivation or environmental stress, even if drugs do not effectively blunt the effects of non-withdrawal-related distress. This view is consistent with findings that suggest that, as addiction becomes more severe, the addicted individual's stress reactions become increasingly similar to his or her reactions to withdrawal and drug cues (Fox et al., 2005; Sinha, Fuse, Aubin, & O'Malley, 2000). Thus, even if addictive drugs do not reduce stress-related distress (AI'Absi, 2007; Conklin & Perkins, 2005; Kassel et al., 2003), generalization may occur across withdrawal- and stress-related distress (Gauvin, Carl, Gouldin, & Holloway, 1993). This postulate extends Wikler's (1948, 1965) concept of conditioned withdrawal to help explain relapses that occur long after pharmacological withdrawal has ended. If interoceptive cues are critical to drug motivation, then the source of interoceptive distress cues (drug withdrawal vs. an external stressor) is less important than the interoceptive state per se. Any event that has the capacity to elicit interoceptive distress cues can trigger self-administration, for example, withdrawal, cues previously paired with drug or withdrawal, or stressors and associated stimuli. This extension of the negative reinforcement model might account for the well-documented effects of exposure to drug cues and priming doses of drug on subsequent drug self-administration (Stewart,

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de Wit, & Eikelboom, 1984). Exposure to drug cues or to smaller-thanexpected doses of drugs may elicit frustration or conditioned withdrawal. Such mild distress may prime drug motivation because, in the past, mild distress predicted even greater withdrawal distress (Hendricks, Ditre, Drobes, & Brandon, 2006). These three modifications to traditional negative reinforcement models account for some of the evidence that challenged traditional negative reinforcement models. How, then, does the new model address the evidence supporting incentive-based or positive reinforcement models (see chap. 2, this volume)? Similar to other negative reinforcement models (Kenny et al., 2006; Solomon, 1977), the reformulated model does not hold that distress is the sole precipitant of urges or self-administration, although it does assert that escape or avoidance of distress is the dominant motive for use. As such, the reformulated model is congenial toward incentive-based models of addiction (Robinson & Berridge, 1993) and acknowledges the role that positive reinforcement plays in drug use, particularly during initiation of use or after a period of abstinence in which tolerance diminishes (Baker, Morse, & Sherman, 1987). Although incentive theorists have tended to assert that distress exerts little effect on drug motivation (e.g., Lyvers, 1998; Robinson & Berridge, 1993), data reveal that distress potently affects the incentive value of drug cues (e.g., Feltenstein & See, 2006). In fact, Robinson and Berridge (1993) acknowledged that background affective distress inflates the salience of incentive cues, beyond the sensitization that occurs directly because of drug effects. Negative reinforcement models make the same prediction but assert that negative reinforcement learning is at least partially responsible for this modulating effect (i.e., that incentives gain value in the presence of distress because past learning has indicated that they are particularly helpful in reducing distress in this context). Such learning could be attributed to either incentive learning, because the incentive value of cues is enhanced, or to negative reinforcement, because the enhancement of incentive value depends on drug self-administration in the context of withdrawal (Hellemans, Dickinson, & Everitt, 2006). In any case, it is clear that taking a drug in the presence of withdrawal distress increases the future likelihood and magnitude of drug selfadministration in the presence of such distress. In summary, the 2004 reformulation of negative reinforcement models strove to reconcile negative reinforcement accounts with extant data and alternative accounts of drug motivation. In so doing, the model suggested that automatic processes drive much of addictive behavior (Palfai, 2006; Tiffany, 1990). This account of drug motivation must then be reconciled with the extensive evidence that conscious processes importantly influence drug motivation. We have recently extended the model by specifying boundary conditions that influence awareness and effortful self-regulation of drug motivation. Next, we review the factors that we posit influence awareness of

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drug motivation and then discuss the research and clinical implications of the integrated modeL

DRUG MOTIVATION AWARENESS BOUNDARY CONDITIONS The initial reformulated model of addiction said little about urges, the subjective experiences of wanting to use drugs, except to indicate that urges were more likely when negative affect was elevated and that the probability of awareness increased as negative affect increased. This simple account failed to reflect the important influence of context on urges. Evidence indicates that exposure to external cues associated with drugs elicits urges among addicted individuals (Carter & Tiffany, 1999) and the degree to which exposure does so predicts self-administration and relapse among those trying to curb drug use (e.g., Marissen et al., 2006). In addition, perceptions of drug availability also modulate the experience of urges, such that addicted individuals who know they will not have access to drugs (e.g., hospitalized smokers) experience fewer urges to smoke than do those who perceive opportunities to use drugs (e.g., Juliano & Brandon, 1998). Any comprehensive motivational account of addiction must account for such contextual influences, and a negative reinforcement model must explain why contextual cues and distress may exert different effects on indexes of drug motivation from one occasion to another. In particular, a comprehensive model must account for why urges and drug self-administration are either poorly correlated with one another or are poorly related to withdrawal magnitude (e.g., Tiffany, 1990). Understanding this lack of coherence demands that knowledge about cognitive control and attentional processing be applied to an understanding of urges. We propose that urges represent an awareness of underlying drug motivation that is driven, at least in part, by negative reinforcement learning. In this model of urges (Curtin et al., 2006), drug motivation is necessary but not sufficient for the experience of urges. This raises questions about the critical boundary conditions that prompt awareness of otherwise-latent motivational processes. To answer this question, we apply basic research on the cognitive control of behavior to the drug use context to generate hypotheses regarding the conditions and factors that make implicit drug motivational processing explicit (Curtin et aL, 2006).

Cognitive Control of Behavior

Cognitive control has been defined as effortful, controlled activation and allocation of attention in order to select and process goal-relevant information that facilitates behavioral adaptation in tasks involving high difficulty,

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novelty, decision uncertainty, or response conflict (Botvinick, Braver, Barch, Carter, & Cohen, 2001; Miller & Cohen, 2001). Cognitive control is crucial to overcome well-learned, habitual responses that are not adaptive, goal relevant, or contextually appropriate. Such maladaptive responses often conflict with more appropriate responses that require support to compete successfully with this strong activation. Cognitive control provides this support by biasing processing in favor of weaker, adaptive responses in the service of the individual's current goals. For example, cognitive control allows individuals completing the classic color-naming Stroop (1935) task to inhibit the welllearned tendency to read words in order to succeed in the task at hand, which is naming the script color of the word. Cognitive control processes are implemented in an anterior attention system that includes structures, such as the anterior cingulate cortex (ACC) and prefrontal cortex (PFC), that receive dopaminergic projections from the ventral tegmental area (Botvinick et al., 2001; Holroyd & Coles, 2002; Miller & Cohen, 2001). (These structures do not constitute the hardware of drug motivational processing, but the involvement of these structures in drug motivation suggests causal paths in such processing.) Cognitive control and the brain systems that govern it can be subdivided into at least two classes of processes. The first class, action-monitoring processes, evaluate the efficacy of current behavioral strategies in real time and titrate the level of (regulative) control to achieve optimal outcomes. The second type, regulative control processes, are recruited to implement top-down biasing of behavior when action-monitoring processes detect that the context demands increased control to support adaptive, goal-consistent behavior (MacDonald, Cohen, Stenger, & Carter, 2000). Recent research on action monitoring has helped identify both its neural substrates and the factors that recruit cognitive control processes. An elegant synthesis of empirical research involving behavioral and functional imaging techniques with theory-driven computational models of response competition paradigms such as the Stroop (1935) color-naming task indicated that detection of response conflict by the ACC plays an important role in action monitoring (Botvinick et al., 2001). Other research that has used event-related brain potentials (in particular, error-related negativity) suggests that action-monitoring processes in the ACC are activated by task errors and negative evaluative feedback about task performance (e.g., Nieuwenhuis, Yeung, Holroyd, Schurger, & Cohen, 2004). Similarly, Holroyd and Coles (2002) documented that outcomes that are generally "worse than expected," including task errors and nondelivery of an expected reward, activate ACC, consistent with its role in action monitoring. Once recruited, regulative control processes are responsible for both the representation and integration of information regarding context and goals in working memory and implementation of top-down attentional control. As

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task-inappropriate responses become more potent, or reinforcement contingencies change, the contribution of regulative control to novel or weaker, but adaptive, responses increases (Botvinick et al., 2001; Yeung, Botvinick, & Cohen, 2004). Nonhuman primate lesion studies and human neuroimaging research strongly implicate the dorsolateral PFC in the working memory processes that are critical for the active maintenance and utilization of both goal and context representations to guide adaptive behavior (Goldman-Rakic, 1987; Miller & Cohen, 2001). The orbital frontal cortex integrates information about future consequences (e.g., S-R associations) and may be critical for adaptive behavior when reinforcement contingencies change (Bechara, Damasio, & Damasio, 2000). The foregoing description indicates that cognitive control is crucial to overcome potent S-R mappings that are not adaptive in the current context. This cognitive control system is a general-purpose executive attention system that is recruited to guide goal-directed behavior across diverse contexts, eliciting stimuli, and S-R complexes. Cognitive control may also be recruited to regulate drug-seeking or self-administration behaviors that are strongly established through negative reinforcement. Indeed, for the dependent drug user pursuing drug abstinence, cognitive control becomes critical in overcoming routinized drug-seeking responses in favor of alternative, less practiced behaviors. Our model suggests that the conditions that recruit cognitive control are ones that also trigger urges among addicted individuals (see Figure 1.1); that is, the operational characteristics of systems affecting cognitive control serve as a basis for deducing factors that influence or produce urges to use drug. Consideration of the various situations and consequences associated with the recruitment of cognitive control provides an explanatory mechanism for many observations about drug use and craving (Curtin et al., 2006). Cue-reactivity research offers preliminary support for the prediction that self-reported urges to use drugs covary with activation of the neural substrates of cognitive control processes. In the cue-reactivity paradigm drug craving is elicited in dependent users by exposing them to various cues that typically co-occur with drug administration (e.g., drug paraphernalia). Neuroimaging research has demonstrated increased activation of key neural structures associated with the recruitment and implementation of cognitive control in this paradigm (see also Franken, Zijlstra, Booij, & van den Brink, 2006). In fact, recent reviews of this literature have concluded that the ACC and sectors of the PFC are the most reliably activated neural structures across cue-reactivity experiments (See, 2002; Wilson, Sayette, & Fiez, 2004). Moreover, several studies have documented that the degree of activation of these neural substrata of the cognitive control system covaries directly with drug craving self-report (e.g., Bonson et al., 2002; Brody et al., 2002) and mental work to resist drug craving (Brody et aL, 2007). As such, research supports the relevance of cognitive control research to awareness of drug motivation in the form of cravings or urges to use.

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Cognitive Control and Awareness of Drug Motivation Our model of the boundary conditions for the recruitment of cognitive control that leads to awareness of urges to use or cravings for drugs is depicted in Figure 1.1. This model proposes that affective distress is a primary setting event for drug motivation and use and that additional factors influence the likelihood that the action monitoring and regulative cognitive control resources described earlier will be recruited and will trigger awareness of the drive to selfadminister drugs. In particular, we propose that high levels of distress, provocative cues (e.g., drug cues of high incentive value), conflict between drug-use and alternative behavioral responses, and surprising outcomes following drug-use or non-drug use behaviors, are positively related to the occurrence of conscious urges to use addictive drugs. In an effort to avoid complexity, some features are not depicted in the model, such as exposure to appetitive drug cues that would also activate approach systems (Ito, Dalley, Robbins, & Everitt, 2002; see also chap. 2, this volume), and the relative weighting of drug use versus other response options, which would affect the likelihood of drug use and conflict occurrence. Our specific predictions are described next. First, we predict that high levels of distress will lead directly to conscious urges to use drugs because both physical and emotional pain invoke cognitive control resources (Botvinick et aL, 2001). Thus, we assert that distress can directly recruit cognitive control, independent of any prior association with drug use. Pain is a salient signal that corrective action is necessary, and the ACC is strongly recruited in response to manipulations that produce both physical pain (Sewards & Sewards, 2002) and psychological distress (Eisenberger, Lieberman, & Williams, 2003). Given that withdrawal is distressing, it is sensible that mounting levels of withdrawal distress will be detected by actionmonitoring processes and recruit increased regulative controL Recent research has implicated the insula, which is involved in interoceptive and exteroceptive detection and processing of errors, emotional distress, and pain (e.g., Critchley, Wiens, Rothstein, Ohman, & Dolan, 2004; Seminowicz & Davis, 2007), in drug craving (Naqvi, Rudrauf, Damasio, & Bechara, 2007). The insula may provide a link between internal distress, including interoceptive signals of distress (Critchley et aL, 2004), and activation of cognitive control processes. Regulative control, once recruited, may result in drug use or abstinence, depending on the addicted individual's current goals. High levels of affective distress may simultaneously recruit and impede regulative control processes (see Tiffany, 1990) because very high levels of distress are likely to invoke stress responses and prompt execution of overlearned flight responses (e.g., avoidance of affect through drug use; Metcalfe & Mischel, 1999). Research supports these hypotheses. Among smokers, for example, mounting withdrawal distress does indeed predict urges (Hendricks et aL, 2006) and relapse (Piasecki et aL, 2003).

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Whereas many studies have revealed reliable relations among withdrawal distress, urges, and drug self-administration, exceptions have also been found (Robinson & Berridge, 1993; Tiffany, 1990). These exceptions reflect the complex relations among these variables. Our model (see Figure 1.1) suggests that, at very low levels of distress, an individual may be guided primarily by automatic processes because the threshold of activation for unconscious drug motivational processing and automatic self-administration is lower than the threshold for cognitive control recruitment. As distress increases, an individual may become aware of the urge to alleviate distress (through drug use) and will consider either the best way to fulfill that urge or the best way to maintain abstinence. At very high levels of distress an individual is very likely to be aware of the affect and associated drug motivation, but regulative cognitive control mechanisms may be compromised so that behavior is likely to be driven by automatic, rather than effortful, processes. Also, the level of drug motivation may be sufficiently great so that regulative control processing supports drug use because the addicted individual consciously concludes that the goal of abstinence is less desirable than the goal of immediate distress relief. These complex distress effects highlight the complexity of relations with urges and self-administration that depend on consideration of other factors, such as weighting of drug use versus other goals (e.g., abstinence). Second, cues associated with incentives of high value (e.g., cues with strong appetitive associations) also tend to engage attention and may recruit cognitive control resources, as indicated by both behavioral and brain electrophysiology measures (Peoples, 2002; Williams, Matthews, & MacLeod, 1996). Among addicted animals and humans, cues associated with their drug of choice have strong incentive values that dwarfs the value of alternative incentives (Robinson & Berridge, 1993, 2003). When very attractive incentives are available, cognitive control resources may be recruited to ensure that the opportunity for reinforcement is not missed (Peoples, 2002).lt is important, however, to avoid the tendency to think of automaticity or cognitive control as dichotomous; instead, both phenomena show gradients of engagement (Cohen et aL, 1990; Cohen, Servan-Schreiber, & McClelland, 1992). Cognitive neuroscience research also suggests that novel incentives are likely to recruit cognitive control resources (see Figure 1.1) and invoke evaluative and regulatory functions in a manner similar to highly valued incentives (Botvinick et aL, 2001). Thus, novel stimuli may temporarily shift attentional focus from drug use. Third, conflict between behavioral response dispositions activated by a set of cues increases the likelihood that drug motivation will enter awareness and demand ongoing processing. In Figure 1.1 we note this by indicating that motivation to engage in nonuse behavioral responses (non-drug use motivation) moderates the relationship between drug motivation and urges to use (recruitment of cognitive control). Response conflict has been shown

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to increase recruitment of cognitive control. As noted earlier, the conflict between the responses of reading text (e.g., "blue") and naming script colors (e.g., "red") in the Stroop (1935) task is a classic example of response conflict. Extensive practice renders reading the dominant response to the presentation of written words. Cognitive control is required in the Stroop task because a person must resist the dominant word-reading response and substitute the less practiced response of color naming. Cognitive control facilitates this shift in response to contextual demands. Negative affect and drug cues are strongly mapped to associated drug-seeking and administration behaviors, much as Stroop color words are strongly mapped to word reading responses. Reinforcement mechanisms and repeated pairings of stimuli and drug-seeking responses across the drug user's career establish a strong mapping between interoceptive withdrawal distress and drug cue stimuli and drug use responses, such that the drug use response has become a "habit" driven by S-R associations (Everitt & Robbins, 2005). When the drug user establishes a drug abstinence goal and reduces drug intake, cognitive control becomes critical for nondrug behaviors to compete successfully with drug use responses activated by distress. In particular, the early stages of quitting are characterized by juxtaposed significant withdrawal-related distress, which primes drug use responses, and motivation to sustain drug abstinence. The conflict between these competing motivations may recruit cognitive control and explain high levels of self-reported craving during early abstinence (e.g., Hendricks et al., 2006). Analogously, the gradual decline in urges with increased durations of abstinence may reflect both the decline of withdrawal distress as well as the increased mapping of nondrug response options. Response conflict surrounding drug use should also occur among nonabstinent drug users and those not striving for abstinence. Some scholars argue that ambivalence about drug use is the basis of addictive behavior (Breiner, Stritzke, & Lang, 1999; Heather, 1998). Any temporary impediment to drug use should occasion conflict, and result in urges, when drug motivation is present. If drug motivation is low, such urges are likely to be transient and to occupy less mental work space than they would at high levels of motivation. In summary, response conflict is likely a daily experience among addicted individuals and is not confined to periods in which access to drugs is blocked or when an individual is trying to curb or cease drug use. Fourth, we expect drug motivation to be experienced as cravings or urges when the outcome of response execution is disappointing or surprising (see Figure 1.1). Electrophysiological and functional imaging studies indicate that both explicit task errors and evaluative feedback about task performance strongly activate the ACC and that this activation is associated with recruitment of the PFC and the execution of corrective behavior (e.g., Gehring, Goss, Coles, Meyer, & Donchin, 1993; Luu, Tucker, Derryberry, Reed, &

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Poulsen, 2003). We predict that this same action-monitoring system will recruit evaluative control when drug effects are either much better or much worse than expected (e.g., when a drink is less relaxing or provides less of a "buzz" than expected), but not when drug effects match expectations. For example, if the effects of the first drink of the night on mood are less potent than a drinker expects, this disappointment may be associated with an increase in the drinker's craving for alcohol. According to this model, the drug motivation that prompted ingestion of the first drink breaks into awareness following its disappointing impact and then spurs additional drinking. Similarly, urges may be caused by tolerance that blunts the direct effect of drug or by switching to a less satisfying form of drug delivery (Hughes, Keely, & Callas, 2005). Evaluative control that is recruited by nondrug responses might also produce urges if such responses are made in the presence of cues with powerful drug use associations. For instance, we predict that coping responses (in lieu of drug use) that do not have the expected effects will increase drug craving. There is some evidence that non-drug use coping responses that are executed to avoid drug use may increase a person's craving and subsequent drug use (Shiffman, 1984). Our model would thus attribute increased awareness of drug motivation in this instance to monitoring of the disappointing outcomes of coping (e.g., inadequate reduction in negative affect). As noted earlier, the factors that increase the likelihood that drug motivation will enter awareness in the form of urges to use are not necessarily the same factors that increase the likelihood of self-administration (Tiffany, 1990; see also chap. 4, this volume). For example, distress may cause an urge, but the relative mapping of drug and nondrug response options may determine whether use occurs. Multiple factors spur the recruitment of cognitive control that may resolve the response conflict in favor of either drug use or an alternative response. In the absence of motivation to engage in an incompatible response, however, drug use would proceed unimpeded without the need for cognitive control or associated awareness of the desire to use. An important point of the foregoing discussion is that conflict between use and nonuse response options does not precipitate urges; it may influence the severity or duration of an urge, but this conflict becomes significant in the context of cues that activate the drug use response (e.g., distress). Figure 1.2 depicts the varied drug motivational outcomes that might arise from a high level of distress as a function of the modulating factors listed earlier. For instance, high levels of distress would be expected to result in strong urges, as depicted in Box A; however, such distress might not be translated into drug self-administration because strong contingencies for abstinence might result in a response weighting in favor of nondrug response options. Box B presents a situation in which weak urges are encountered because the drug use response option is so heavily weighted that little conflict occurs and drug use ensues quickly. Box C represents a situation in which

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Distress

I

I A

B

C

Strong Urges

Weak Urges

Strong Urges

+

+

+

Low Drug Intake Likelihood

High Drug Intake Likelihood

High Drug Intake Likelihood

Figure 1.2. Diverse theory-based outcomes of distress. One criticism of negative reinforcement models of drug motivation has been that distress is not consistently related to urge magnitude or drug use likelihood. This may occur because the relation of distress with urge and drug use is moderated by factors such as drug availability and level of response conflict. For instance, Box A reflects a pattern that occurs when high motivation to abstain causes great response conflict (along with distress) and low likelihood of drug use. The pattern depicted in Box B might occur because low reasons to abstain result in little response conflict and drug availability result in drug use. The pattern of Box C might occur because the presence of drug cues (along with distress) might recruit increased cognitive control resources and strong urges, even though drug use is imminent.

distress is present and a potent incentive cue activates anterior attentional control systems, which produces strong urges, but an absence of response conflict allows drug intake to occur unimpeded. This simple schematic reveals that a cognitive control information-processing model may be helpful in elucidating the sort of influences that can account for distinct covariation patterns among such variables as distress, urges, and drug use. In summary, the conditions that we assert are most likely to predict awareness of drug motivation (i.e., urges) are high levels of distress, exposure to cues of great incentive value, response conflict, and detection of surprising response outcomes. We assert that the recruitment of cognitive control mediates the effects of these factors on urges. These predictions are grounded in recent findings regarding the neural substrates of cognitive control and represent a refinement of our negative reinforcement model of drug motivation. This refined model in tum allows us to make more specific predictions about the circumstances under which self-reported urges to use drugs will reliably index drug motivation and predict self-administration.

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Each of the three proposed negative reinforcement model modifications just described suggests that research methods used to test the model need to be updated. The hypothesis that withdrawal-induced negative affect is the motivational core of drug addiction suggests that we need to refine our assessments of the affective components of withdrawal and separate these affective symptoms from other withdrawal components when testing distress-relapse relations (e.g., McCarthy, Piasecki, Fiore, & Baker, 2006; Sofuoglu et al., 2005). When testing withdrawal-use relations, the potential moderating effect of conflicting response motivation and drug cues may also need to be taken into account because we predict that drug use may be very likely in the context of low distress, if drug cues are present and response conflict is low. In addition, the importance of unconscious motivational processing in the reformulated model suggests that self-report measures are likely to be insensitive to the very early signs of affective withdrawal. Implicit measures of both affective processing and drug motivation are therefore essential in future tests of the model. Although such measures exist, their reliability and validity have not been established (e.g., De Houwer, 2006; Fiedler, Messner, & Bluemke, 2006; Schmukle, 2005). Furthermore, our model suggests that the validity of self-report urges may be moderated by the conditions that influence awareness of drug motivation. For example, individuals should be able to report drug motivation more accurately when distressed, in the presence of highvalue incentives, when they are experiencing response conflict, or when they are disappointed with outcomes. As such, the validity of self-report assessments is likely to vary across contexts and time.

CLINICAL IMPLICATIONS OF THE REFORMULATED NEGATIVE REINFORCEMENT MODEL The reformulated model and boundary conditions for awareness of drug motivation described earlier suggest several behavioral routes to facilitating change in addictive drug use. (We will ignore for now pharmacologic routes that reduce the negative affect or anhedonia produced by withdrawal [Piper et al., 2008] and therefore reduce the motivational press to use.) The first route to change focuses on altering directly the S-R mappings that sustain addictive drug use. The second route focuses on strengthening cognitive control. An optimal treatment strategy might involve both the first, bottom-up route, and the second, top-down route. With time and practice, drug abstinence in the presence of cues formerly associated with drug use should become the default, automatic response (Palfai, 2006). The reformulated model suggests that mapping of drug use responses to interoceptive signals of activity in negative affect systems is the primary basis for continued drug use. Given this, Pavlovian extinction involving repeated

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exposure to interoceptive cues of negative affect without drug use should weaken the distress-drug use mapping. Distress would still elicit cognitive control following extinction, but extinction would shift the balance of response mapping in favor of nondrug response options. Past interventions based on extinction have attempted to weaken the link between external cues and drug effects, with limited success (e.g., Conklin & Tiffany, 2002). Pilot research in opiate users suggests that extinction to internal cues may be more effective, at least for women (Pollack et al., 2002). In addition, operant conditioning could be used to train addicted individuals to execute drug-incompatible responses in the presence of distress cues. Contingency management programs alter the contingencies for drug use overall (so that abstaining yields positive reinforcers) and lead to significant decreases in drug use (Higgins, Roll, Wong, Tidey, & Dantona, 1999). Strong rewards for eschewing drugs would also lead to decreased drug urges to the extent that the rewards reduced response conflict by overwhelming the attractiveness of the drug use response. In either the case of extinction or operant conditioning of alternative responses, however, the key to success will be the individual's extensive practice of alternative responses across diverse internal and external contexts (Otto, Powers, & Fischman, 2005). Such repetition will be essential to compete with the overlearned, strongly mapped response of drug-seeking in various contexts. The present model also suggests that it may be helpful to extensively rehearse nondrug responses to negative affect and urges to use before attempting to change drug use. Response conflict increases the likelihood that drug motivation will enter awareness and that prefrontal cognitive control resources will be recruited to resolve the conflict. As such, increasing response conflict by strengthening connections between drug use instigators and nondrug responses prior to a behavior change attempt may help people resolve urges without using drug. Massed pre-cessation execution of competing responses should have several effects. Whereas it might increase urges (because the alternative response options would become more balanced with drug use responses), the increased mapping of the nondrug response may make its execution more likely once cognitive control is engaged-that is, urges would be increased, but drug use would be less likely. Finally, pre-cessation execution might make the individual thoroughly familiar with the consequences of the nondrug response and thus make it less likely to yield disappointing effects that can increase urges. Seen in this light, the individual would be better off to practice extensively only a few nondrug responses versus a menu of diverse responses. The danger that inappropriate expectations about nondrug responses might foster greater urges suggests that, instead of touting the benefits of alternative behaviors (coping responses) in treatment, perhaps clinicians should, paradoxically, promote more modest expectations of relief or reward regarding the outcomes of their coping efforts. Surpassing low expectations is associated with greater satisfaction with change than is failing to meet high expectations,

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and satisfaction predicts maintenance of behavior change (Baldwin et al., 2006). These findings suggest that it may be helpful to temper rather than enhance clients' expectations regarding the outcomes of effortful coping, in particular once they have decided to try to change. Even extensive training in alternative responses and changes in response contingencies are not likely to be sufficient to promote lasting change in addictive drug use. Effortful processing may also be helpful in preventing drug motivation and self-administration. For example, selecting environments that offer few opportunities to use drug and that have few associations with use may serve as an urge and use prevention strategy (see also chap. 11, this volume). Rather than relying on effortful cognitive control resources to help when one is already in trouble (i.e., when drug motivation has already been activated and drug opportunities are available), one can use cognitive control resources to minimize the risk that automatic drug use will occur (Palfai, 2006). In fact, evidence suggests that this strategy (i.e., avoiding drug use triggers) is effective in helping individuals achieve long-lasting abstinence (Fiore et al., 2000). However, the current conceptualization suggests particular reasons why this approach may be beneficial in addition to the usual notions that it reduces elicitation of drugconditioned responses. One reason is that avoiding triggers does not rely on awareness of drug motivation. Another benefit is that reducing drug motivation and opportunities for use is likely to reduce demand for limited cognitive control resources. Research suggests that self-control failures are especially likely after completing earlier tasks that demand self-control (Muraven & Baumeister, 2000). This makes sense given the finite nature of cognitive control processes mediated by the ACC and PFC and their susceptibility to fatigue (Falkenstein, 2004), and therefore it makes sense to conserve resources by avoiding unnecessary demands on this system. Individuals may become worn out or fatigued from using cognitive control resources continuously as they relearn daily routines by constantly substituting effortful responses for automatic ones (Piasecki, Fiore, McCarthy, & Baker, 2002). Any treatment strategy that relies on cognitive control must take into account variability in the recruitment and execution of controlled processing across individuals and situations. Research indicates that cognitive ability in areas such as memory and various dimensions of executive functioning moderate alcoholics' responses to treatment (Bates, Pawlak, T onigan, & Buckman, 2006). According to our model, individual differences or states that mark impaired recruitment or implementation of cognitive control will be associated with increased probability of drug use when the individual is exposed to negative affect or drug cues (i.e., trait or state reductions in cognitive control activation are associated with increased drug use probability when pursuing drug abstinence; e.g., Naqvi et al., 2007). Recent research has demonstrated that individuals who show greater biases toward drug-related cues in modified Stroop tasks (i.e., who take longer to color-name drug-related vs. neutral words of

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motivational relevance), presumably because of weaker cognitive control, have more difficulty in subsequent abstinence attempts (Cox, Hogan, Kristian, & Race, 2002; Waters et al., 2003). This interference may reflect multiple influences, including weaker cognitive control, but more research is needed to support this interpretation. In addition, it is important for research to examine the role of distress in modulating the effective exercise of cognitive control, inasmuch as there is strong evidence that it is precisely when individuals are distressed that they are most likely to relapse (e.g., Kassel et al., 2003). Distress tolerance is another individual difference of note in addiction. Research on distress tolerance has provided data linking individual differences in cognitive control with drug use probability (Brown, Lejuez, Kahler, Strong, & Zvolensky, 2005). In distress tolerance studies, drug users are instructed to perform stressful behavioral or mental tasks (e.g., solving difficult anagrams). Drug users presumably experience conflict between adhering to instructions to persist at the task and motivation to terminate the aversive experience. Thus, duration of task persistence may be a proxy for successful application of topdown control. Consistent with this notion, decreased ability to persist on the aversive tasks is associated with decreased duration of abstinence among smokers (Brandon et al., 2003) and users of other substances (Daughters, Lejuez, Kahler, Strong, & Brown, 2005). Other interpretations are possible, but the phenomenon is also consistent with a cognitive control explanation. In clinical settings, it may be important to identify people who are slow to recruit cognitive control or exercise control ineffectively. Treatments can be tailored for such individuals to emphasize bottom-up change strategies such as those listed earlier. Some recent research has shown promising outcomes in the training of enhanced executive function in various patient populations (e.g., computer assisted remediation; Elgamal, McKinnon, Ramakrishman, Joffe, & MacQueen, 2007; Kurtz, Seltzer, Shagan, Thime, & Wexler, 2007). In addition, it may be important to educate individuals about situations that diminish the effectiveness of cognitive control, such as intoxication (e.g., Curtin & Fairchild, 2003). Impairment in top-down attentional control process has been implicated in the general increase in behavior regulation problems observed among intoxicated individuals (e.g., aggression, impulsive risk taking; Steele & Josephs, 1990). Alcohol impairment of cognitive control may account for the increased risk for relapse to smoking when intoxicated (Krall, Garvey, & Garcia, 2002). Abstaining smokers who are in a bar or drinking context will frequently encounter smoking cues that activate strong motivation to smoke. If cognitive control processes are acutely compromised by alcohol intoxication, these smokers will not be successful in inhibiting smoking motivation and will fail to maintain abstinence. The current perspective yields the prediction that alcohol intake will increase drug use but not urges. In summary, the reformulated model suggests that success in changing drug use may be enhanced by changing S-R mappings and associated expectancies

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regarding the impact of nondrug reinforcers, particularly for interoceptive cues of distress, prior to attempts to permanently change behavior. In addition, the model highlights the relative unavailability of drug motivational processing for introspection and conscious control and the importance of developing awareness of drug motivation before it prompts strong drug urges or use. A treatment package based on this model of addiction would differ considerably from existing treatments, although some traditional treatment components, such as encouraging people to reduce exposure to drug triggers, especially those involving distress, would remain the same. In general, this model stresses the importance of preparing for a change attempt both behaviorally and cognitively and suggests that reliance on effortful coping and regulatory cognitive control mechanisms will not be helpful for people with relatively nonresponsive or ineffective cognitive control processes. Unfortunately, compromised cognitive control may be relatively common among populations of addicted individuals (Ersche, Clark, London, Robbins, & Sahakian, 2006; Verdejo-Garda & Perez-Garda, 2007).

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2 POSITIVE REINFORCEMENT THEORIES OF DRUG USE HARRIET DE WIT AND LUAN PHAN

Drugs of abuse exert their actions in the brain on the same neural circuits that subserve natural reward, a construct often considered to be synonymous with positive reinforcement (Koob & Bloom, 1988; Koob & Nestler, 1997; Wise, 1980, 1996). Both drugs of abuse and natural rewards, such as food and sex, activate the mesolimbic dopaminergic pathway. In humans, drugs of abuse also produce positive affective states that resemble the states experienced during naturally occurring positive emotions, raising the possibility that the same neural mechanisms involved in positive emotionality may also be involved in drug-use behavior. Most research on the neurobiology of drug-taking behavior is based on studies of laboratory animals. Although these preclinical studies have greatly advanced our understanding of the behavior of drug seeking, they are less suited to investigation of the subjective experiences produced by drugs, including euphoria, heightened affective states, and positive emotions. Thus, relatively little is known about how drugs or drug-related cues affect emotional processes in humans, even though the euphorigenic and affective Preparation of this chapter was supported by Grants DA02812 and DA09133. From the National Institutes of Health. We thank Gillinder Bedi and Chris-Ellyn Johanson for helpful comments on the chapter.

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effects of drugs may be central to their rewarding effects in humans. There recently has been an increased interest in the role of positive (and negative) affect in drug-seeking behavior. In addition, imaging techniques now widely used in affective neuroscience offer a rich source of information about the neural circuits involved in positive affective states, knowledge that can be applied to our understanding of drug use (see also chap. 11, this volume). These imaging studies characterize the neural circuitry underlying the perception, experience, and memory of positive or pleasurable stimuli. In this chapter, we review the role of positive affect in drug-taking. First, we review the idea that drugs are used mainly for their rewarding, or positive reinforcing, effects. Then we briefly review recent empirical findings about the relationship between positive affect and drug-taking, and between cues and positive affect. Finally, we review recent evidence from affective neuroscience regarding the neural basis of affective processes involved in drug-seeking behavior.

BEHAVIORAL AND NEUROBIOLOGICAL MECHANISMS OF DRUG REWARD Early drug self-administration studies conducted with laboratory animals demonstrated unequivocally that most drugs of abuse can function as positive reinforcers in much the same way as classic positive reinforcers such as food or water (Deneau, Yanagita, & Seevers, 1969; Henningfield, Lukas, & Bigelow, 1984; Thompson & Schuster, 1964). The patterns of acquisition, intermittent reinforcement, extinction, and reinstatement of drug-reinforced responding resemble patterns of responding for traditional rewards (de Wit, 1996; Goldberg, 1973; Pickens, Meisch, & Thompson, 1978; Spealman & Goldberg, 1978). These findings were contrary to a common conception, based on early clinical impressions, that drug-taking is mainly motivated by negative reinforcement, or relief of withdrawal (Stewart & Eikelboom, 1981; Wikler, 1961). In the 1970s and 1980s, a large body of parametric research on the behavioral aspects of drug self-administration accumulated, laying the groundwork for later studies investigating the neurobiological basis of drug reward. These studies described the role of dose, reinforcement schedule, conditioned stimuli, extinction, and many other features of drug-reinforced behaviors, further supporting the view that drug-seeking related mainly to the positive, or desirable, effects of drugs instead of avoidance of a negative state. The resulting literature provided a solid empirical basis for researchers to investigate the neurobiological mechanisms that underlie drug-seeking behavior. In parallel, controlled laboratory studies of drug-taking were also conducted with humans, with procedures that were similar to those used with animals. These studies initially were conducted from a purely behavioral point of view, without reference to any inferred underlying internal states

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or processes (e.g., Fischman & Schuster, 1982). There was an excellent correspondence between the behavior maintained by drugs as reinforcers in humans and in nonhumans, supporting the idea that similar processes of positive reinforcement maintain drug-seeking across species (Henningfield et al., 1984). Later, studies with humans incorporated measures of selfreported subjective states, indicating that the positive reinforcing effects of self-administered drugs are accompanied by feelings of well-being or euphoria. Modern research on the neurobiological mechanisms underlying drug reward grew from investigations of rewarding electrical brain stimulation in laboratory animals. The discovery that animals would learn to press a lever to obtain small pulses of stimulation in certain brain areas led to the idea of a reward center, or reward circuit, in the brain (Olds & Milner, 1954). Researchers discovered that the main neuroanatomical pathway supporting rewarding brain stimulation was the medial forebrain bundle, and further research indicated that the neurotransmitter system critically involved in brain stimulation reward was dopamine (DA; Wise & Bozarth, 1985). They also found that most drugs of abuse decreased the threshold for brain stimulation reward, suggesting that they acted on the same dopaminergic system (Wise, 1985). Since then, a convergence of neurochemical, electrophysiological, and behavioral data indicates that most drugs that are abused by humans and selfadministered by animals elevate DA levels in the nucleus accumbens (e.g., amphetamine, cocaine, nicotine, opioids, alcohol, marijuana; Koob & Nestler, 1997). This finding, together with the observation that most drugs of abuse also produce feelings of positive affect in humans, led to the idea that DA mediates drug-induced hedonia. This led to an initial working hypothesis that the DA system mediated the hedonic and rewarding effects of all positive reinforcers, including drugs and natural rewards (Wise, 1980). In the 1990s, evidence against the hedonia hypothesis began to accumulate. For example, DA receptor antagonists, such as pimozide, failed to block the euphorigenic effects of stimulant drugs in healthy human volunteers (Brauer, Goudie, & de Wit, 1997). Most influential was the research conducted by Berridge and Robinson (1998), who argued that the immediate pleasurable effects of stimuli, or "liking," could be dissociated from seeking of the stimuli, or "wanting," and that compulsive drug use was more related to wanting than to liking. Berridge and Robinson noted that the locomotor effects of stimulant drugs in animals become more pronounced with repeated administration of the drug, and they applied this idea to drug dependence. They postulated that the escalation in motor responses was similar to the observed progressive increase in the incentive salience, or motivational significance, of stimuli related to administration of the drug. The incentive salience theory postulates that wanting of a drug, elicited by environmental cues associated with the drug, escalates through the process of conditioning, even if liking of the drug does not increase, and may even

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decrease. In this way, Berridge and Robinson proposed that drug-related cues acquire strong conditioned incentive properties that come to control the organism's behavior. Another model that has received considerable attention postulates a reward learning hypothesis, with DA playing a key role in "stamping in," or reinforcing, responses that are followed by rewards (Everitt & Robbins, 2005). This may occur either by strengthening processes of stimulus-stimulus pairings (Le., Pavlovian conditioning) or by strengthening stimulus-response habits that lead to rewards (Le., operant conditioning). A specific form of reward learning forms the basis of the prediction error hypothesis, which is based on patterns of the firing of DA neurons during reward-related behaviors (W. Schultz, 1998,2006; W. Schultz, Dayan, & Montague, 1997; W. Schultz, Tremblay, & Hollerman, 1998). These authors have shown that DA neurons in the striatum, frontal cortex, and amygdala fire under specific conditions, suggesting that they serve a function of predicting reward; that is, they are active when an unconditioned rewarding stimulus is presented, or in anticipation of a reward predicted by a conditioned stimulus, but not when an expected unconditioned rewarding stimulus occurs. Thus, exogenously administered drugs (Le., drugs of abuse) that perturb or activate this system may produce a false or exaggerated signal for an upcoming rewarding stimulus. For example, in humans, the direct effects of drugs, such as cocaine, may amplify the motivational significance of environmental cues that are associated with availability of the drug (e.g., drug-taking paraphernalia). W. Schultz (2002) postulated that this reward signaling function complements other, more tonic processes, which direct the reward-related signal to the behavior that is appropriate for the situation. He drew an interesting analogy between this reward-alert signal and certain theories of emotion (e.g., LeDoux, 1996, 2000) that postulate that emotion-inducing states are initially nonspecific and acquire distinctive feelings and response tendencies only when they are combined with more specific cognitive representations. Thus, to the extent that abused stimulant drugs activate the phasic DA system, they may result in drug-seeking behaviors only in a context where the reward signal can be directed to appropriate behaviors.

RELATIONSHIPS BETWEEN POSITIVE AFFECT AND DRUG USE The evidence just described suggests that drugs increase positive affect and produce reward-related motivational states. A related issue is how affective states themselves facilitate the use of drugs and whether environmental events that increase positive or negative affect also increase the likelihood of using drugs, just as drug-related cues do. In the following section, we review

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evidence that positive affect can set the occasion for continued or renewed drug-seeking behavior and that the facilitatory effects of drug-related cues may also engage affective processes. Several studies have examined the bidirectional relationships between subjectively experienced positive affective states and drug use. As we noted in the preceding section, most drugs that are abused, perhaps with the exception of nicotine (Kassel et al., 2007), produce feelings of well-being and positive mood, which may be synonymous with naturally occurring positive affect. Several studies have examined whether positive affective states unrelated to drugs increase the tendency to use drugs in nondependent volunteers or abstinent, dependent users and whether drug-related cues increase positive affect. The findings of studies that have addressed these questions are complex, and they vary with methodological factors and across drug classes. Here, we discuss some examples of research in this area. The evidence that positive affect can precipitate relapse is mixed. In one study, Shiffman et al. (2002), using ecological momentary assessment, found that momentary increases in positive or negative affect did not consistently lead to relapse to smoking in abstinent smokers. However, in other studies (Baer & Lichtenstein, 1988; Shiffman, 1982, 1986), positive affect was associated with relapse to cigarette smoking. Similar findings have been found with regard to cocaine (McKay, Rutherford, Alterman, Cacciola, & Kaplan, 1995). There is also a large body of evidence showing that, in humans and nonhumans, small priming doses of a previously self-administered drug increase reinstatement of drug-seeking (de Wit, 1996; Shaham, Shalev, Lu, de Wit, & Stewart, 2003 ). To the extent that self-administered drugs produce positive affect, this is consistent with the idea that positive affective states may facilitate relapse. Positive affect may also facilitate drug use in nondependent individuals.In laboratory-based studies, we and others (Acheson, Mahler, Chi, & de Wit, 2006; Cousins, Stamat, & de Wit, 2001; Higgins, Roll, & Bickel, 1996) have found that drugs that increase positive mood states, including cocaine, d-amphetamine, and alcohol, and sometimes nicotine, can increase the likelihood of ingesting other drugs. For example, we found that transdermal nicotine increased positive mood and increased alcohol consumption in a choice test in male light smokers, but not in women (Acheson et al., 2006). Higgins and colleagues (1996) showed that acute doses of cocaine increased self-administration of alcohol, and Cousins et al. (2001) showed that d-amphetamine, which produces feelings of well-being and positive mood, increased consumption of cigarettes in a laboratory choice procedure. Several studies (King & Epstein, 2005; Sayette, Martin, Wertz, Perrott, & Peters, 2005) have reported that alcohol increased craving for cigarettes, and there is some evidence that this effect is mediated by alcohol-induced increases in positive mood states.

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A further question is whether drug-related cues increase positive affect, thereby increasing the likelihood of drug use. The question of whether drug cues increase positive affect (similar to the drug itself) or produce negative affect (opposite to the drug) touches on a long-standing and still-unresolved issue about the direction of conditioned drug effects (Eikelboom & Stewart, 1982). The effects of drug-related cues on affect are complex and probably depend on the conditions of testing. For example, the effects of cues may depend, in part, on the motivational state of the individual. Payne, McClemon, and Dobbins (2007) recently reported that cues that have been paired with smoking produced favorable emotional states in smokers, but only in those who were highly motivated to smoke and not in a state of acute nicotine withdrawal. Little is known about the relation between cue-induced positive affect and drug-taking behavior. Heinz et al. (2007) examined limbic brain activation elicited by briefly presented alcohol-associated stimuli in abstinent alcoholic participants. Surprisingly, individuals who displayed higher limbic brain activation during affectively positive but not negative stimuli were less likely to relapse, suggesting that positive affective responses to cues may be protective, although the study did not measure self-reported affective states after the stimuli. The interactions between cues and positive affect are an important area for future research.

NEUROSCIENCE OF POSITIVE AFFECT Drug addiction typically has been studied on the basis of behavioral neuroscience research conducted with nonhuman species, with few studies directly addressing the neural substrates underlying the subjectively experienced emotional and motivational changes associated with drugs in humans. As noted earlier, drugs of abuse exert euphorigenic (mood-elevating) effects perhaps by acting on reward centers of the brain (Kalivas & Nakamura, 1999; Kalivas & Volkow, 2005), which may be related to the neural processes that mediate positive affect. By understanding the neural mechanisms of positive affect in humans through the use of brain imaging techniques, we may improve our understanding of the internal processes that contribute to the initiation and maintenance of drug taking. Positron emission tomography and functional magnetic resonance imaging provide measures of blood flow/oxygenation changes as an index of functional brain activation in response to emotional probes. These techniques allow researchers to localize emotional perception and experience in specific brain areas/circuits in humans (Davidson, Abercrombie, Nitschke, & Putnam, 1999; Phan, Wager, Taylor, & Liberzon, 2002; Phillips, Drevets, Rauch, & Lane, 2003) and to compare findings based on humans with the far larger literature based on laboratory animals.

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Affective neuroscientists have conceptualized positive affect not only as hedonic feelings but also as behavioral and physiologic changes that guide the pursuit, attainment, and enjoyment of rewards. As such, positive affect has been studied as subjective experiences/feelings of pleasant emotions (hedonia), tendencies to approach and acquire things known to evoke hedonic responses (e.g., reward seeking; Frijda, 1986), and increases in peripheral and central reactions to pleasant stimuli (Lang, Bradley, & Cuthbert, 1998; Lang, Greenwald, Bradley, & Hamm, 1998). Affective experience may be characterized on a dimension of good-bad feelings (e.g., Positive and Negative Affect [Davidson, 1995]), and the positive affect component of this dimension may be related to the subjective feelings of euphoria, elation, and being high induced by drugs of abuse. In affective neuroscience research, three aspects of transient positive affective states have been studied: evaluative (e.g., perception of stimuli that evoke pleasant feelings and motivate approach behaviors), experiential (e.g., the experience of those pleasant feelings), and cognitive (e.g., learning to predict and anticipating pleasant feelings). Positive affective states are typically measured with self-report Likert-type rating scales or by examining unconditioned behavioral responses. For example, emotional states evoked by viewing pictures that elicit pleasant feelings can be assessed using a pictorial symbol or a verbally anchored scale (e.g., low vs. high positive valence; Lang et al., 1993); alternatively, positive emotional states can be quantified by the presence of distinctive features of facial musculature thought to reflect genuine positive emotion (Ekman, 2003). Affective neuroscientists have begun to elucidate the neural basis of the processes involved in perception, experience, response, and anticipation of positive affect (Barrett, 2006; Gross, 2002; Phillips et al., 2003). The neural circuits most strongly implicated in these functions are the ventral striatum (including the nucleus accumbens), orbitofrontal cortex, and amygdala, which coincide closely with the regions implicated in the mood-elevating effects of drugs of abuse. Drugs of abuse may act on these emotional systems through a number of processes. Drugs may lower the threshold to achieve positive affect, or they may enhance the intensity or duration of positive affective experience. The initial stage of positive affect involves the perception and evaluation of pleasurable stimuli. Mesolimbic brain regions (ventral striatum, nucleus accumbens, amygdala) and the orbitofrontal cortex are activated in response to tasting sweet chocolate (Small, 2002; Small et al., 2003), viewing attractive faces (Aharon et al., 2001), listening to pleasurable music (Blood & Zatorre, 2001; Blood, Zatorre, Bermudez, & Evans, 1999), and viewing erotic scenes/movies (Redoute et al., 2000) and pleasant pictures (Garavan, Pendergrass, Ross, Stein, & Risinger, 2001; Hamann, Ely, Hoffman, & Kilts, 2002; Uberzon, Phan, Decker, & Taylor, 2003). In laboratory animals, meso limbic structures are activated when animals detect reward and

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represent reward-related goals (striatum), and the orbitofrontal cortex is involved in the representation of reward value (magnitude and value; Rolls, 2000; R. T. Schultz et al., 2003). The amygdala/extended amygdala has also been implicated in reward responding in studies conducted with laboratory animals (Baxter & Murray, 2002; Gilbert & Kesner, 2002; Paton, Belova, Morrison, & Salzman, 2006). As we noted earlier, responses to drug-related cues (Tiffany & Carter, 1998; Tiffany, Carter, & Singleton, 2000) may also involve the perception and detection of pleasurable stimuli. Drug-related cues in addicted individuals elicit subjective feelings of craving, or wanting to use a drug (Tiffany & Carter, 1998; Tiffany et al., 2000; see also chap. 4, this volume). Consistent with the idea that cues induce conditioned positive responses, functional brain imaging evidence suggests that the circuits implicated in detection and visual processing of drugrelated cues are the same as those activated in response to non-drug-related pleasurable stimuli. The mesolimbic-mesocortical reward circuit (including the striatum, accumbens, amygdala, and orbitofrontal cortex) is engaged by visual cues designed to elicit craving for tobacco (David et al., 2005; McClernon & Gilbert, 2004; McClernon, Hiott, Huettel, & Rose, 2005), heroin/opiates (Sell et al., 2000), and cocaine (Bonson et al., 2002; Kilts, Gross, Ely, & Drexler, 2004). Of interest is that administration of cocaine in cocaine-dependent individuals modulated the activity of the nucleus accumbens and amygdala, and the extent of activation was correlated with craving ratings (Breiter et al., 1997). Conversely, DA antagonists have been reported to reduce cue-induced craving in addicted individuals (Berger et al., 1996; Smelson, Roy, & Roy, 1997). As such, DA may trigger the brain's attention toward appetitive stimuli as represented by drug-related cues (Franken, 2003). Thus, the circuits that mediate craving overlap substantially with those that mediate processing of other non-drug-related pleasurable stimuli and reward. Positive subjective experiences are elicited by detection of both drug and nondrug rewarding/pleasurable stimuli, and perhaps by cues associated with such stimuli. It is interesting that similar regions, such as the nucleus accumbens and the ventral striatum, appear to be engaged during the positive emotions elicited by such diverse experiences as winning money/ getting a financial reward (Breiter, Aharon, Kahneman, Dale, & Shizgal, 2001; Delgado, Locke, Stenger, & Fiez, 2003; Elliott, Newman, Longe, & William Deacon, 2004; Knutson, Fong, Adams, Varner, & Hommer, 2001), playing enjoyable video games (Koepp et al., 1998), recalling and imagining positive life events (Damasio et al., 2000), and experiencing orgasmic pleasure following ejaculation (Holstege et al., 2003). Consistent with this notion, the mood-elevating (euphorigenic) and pleasurable effects of drugs of abuse also activate predominantly dopaminergic meso limbic brain regions (Kalivas & Volkow, 2005). For example, the extent of ventral striatal DA receptor binding induced by dopaminergic psychostimulants is correlated

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with self-reported ratings of a subjective high (Volkow et al., 1997), and feelings of euphoria after amphetamine are correlated with amphetamineinduced DA release in the ventral striatum (Drevets et al., 2001). As we noted earlier, dopaminergie agonists or drugs that increase DA levels lower reward thresholds in animal brain stimulation models (Le., increase reward; Cryan, Bruijnzeel, Skjei, & Markou, 2003). In humans, DA agonists, including drugs of abuse such as amphetamine, modulate meso limbie brain activity in response to emotional cues (Hariri et al., 2002; Tessitore et al., 2002). Amphetamine also enhances arousal responses to monetary gains (Knutson et al., 2004), supporting the idea that drugs of abuse act on the same neural circuits that mediate nondrug rewards. Whether similar effects also occur with other classes of abused drugs remains to be determined. There is also indirect evidence that the experience of positive affect during rewarding experiences activates the mesolimbic brain regions in laboratory animals, even though subjective experiences associated with rewards cannot be assessed directly in animals. One behavioral measure thought to reflect positive affect in rats is 50-kHz ultrasonic vocalizations (Burgdorf & Panksepp, 2006). These vocalizations are modulated by DA (Knutson, Burgdorf, & Panksepp, 2002). Another measure used to assess positive affect is the distinctive stereotypical oral-facial expressions elicited by sweet solutions. These responses are elicited in rodents, human infants, and adult nonhuman primates, suggesting that there is cross-species generality in positive hedonic taste reactivity (Berridge, 2000; Steiner, Glaser, Hawilo, & Berridge, 2001). Microinjections of drugs that activate mesolimbic-mesocortical "hedonic hotspots" (Berridge & Kringelbach, 2007) have been shown to enhance these positive reactions to sweet tastes and are associated with increased intake of sweet rewards (Mahler, Smith, & Berridge, 2007; Pecifia & Berridge, 2000, 2005; Smith & Berridge, 2005, 2007). Thus, there is indirect evidence to support the idea that pleasurable experiences of both drug and nondrug stimuli activate the mesolimbic DA system in animals, just as they do in humans. Another link between positive affect and reward-motivated behaviors involves cognitive processes (anticipation, learning, decision making) related to the reward. In humans and other primates, the expectation and prediction of rewards appear to be coded by the ventral striatum and orbitofrontal cortex (Breiter et al., 2001; Knutson, Adams, Fong, & Hommer, 2001; Knutson, Fong, et al., 2001; Pagnoni, Zink, Montague, & Berns, 2002; Rolls, 2000; R. T. Schultz et al., 2003). Indeed, research suggests that the mesolimbicmesocortical DA system mediates learning and prediction about reward, serving to strengthen, or reinforce, certain behaviors (Bayer & Glimcher, 2005; Di Chiara & Bassareo, 2007; W. Schultz et al., 1997). These functions are thought to be mediated by the nucleus accumbens and related striatal brain

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regions (Barnes, Kubota, Hu, Jin, & Graybiel, 2005; Carelli, 2004). It has been hypothesized that people addicted to drugs may be impaired at making cost-reward calculations and that they may fail to maximize rewards, given that they prefer to engage in drug-seeking behaviors over actions that ultimately result in more favorable outcomes. Empirical studies of such processes investigate temporal discounting, or preference for immediate over delayed rewards of larger value, a tendency related to impulsivity and that may be a risk factor for addictive disorders. In support of this idea, individuals who exhibit a greater preference for smaller, immediate (over larger, but delayed) rewards also exhibit greater activity in the ventral striatum/nucleus accumbens (Hariri et a1., 2006; McClure, Laibson, Loewenstein, & Cohen, 2004). On perhaps a related note, patients with cocaine addiction exhibit dampened corticolimbic reward circuit responses when making decisions about monetary rewards (Goldstein, Alia-Klein, et a1., 2007; Goldstein, Tomasi, et a1., 2007). Decision making and sensitivity to future consequences have also been linked to orbitofrontal functioning (Bechara, Damasio, & Damasio, 2000; Bechara, Damasio, Damasio, & Anderson, 1994), and opiate and heroin users exhibit both impaired risk-reward judgments and hypofunction of orbitofrontal activity (Ersche et a1., 2005, 2006). CONCLUSIONS We have reviewed evidence for the idea that drugs of abuse produce positive reinforcing or rewarding effects, which correspond to feelings of positive affect in humans. In laboratory animals, drugs of abuse control behavior in much the same way as other, natural rewards, such as food or sex. Drugs activate mesolimbic reward pathways in laboratory animals, and recent imaging studies with humans suggest that they also stimulate affective circuitry related to reward and positive affective states in humans. There is also some evidence that drug-related cues similarly activate the neural substrates for both reward and positive affect. Taken together, these findings provide support for the view that drug-taking is, at least in part, related to the drugs' actions on neural circuits of positive affect. REFERENCES Acheson, A., Mahler, S. V., Chi, H., & de Wit, H. (2006). Differential effects of nicotine on alcohol consumption in men and women. Psychopharmacology (Berlin), 186,54-63. Aharon, I., Etcoff, N., Ariely, D., Chabris, C. F., O'Connor, E., & Breiter, H. C. (2001). Beautiful faces have variable reward value: fMRI and behavioral evidence. Neuron, 32,537-551.

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3 COGNITIVE THEORIES OF DRUG EFFECTS ON EMOTION JON D. KASSEL, MARGARET C. WARDLE, ADRIENNE J. HEINZ, AND JUSTIN E. GREENSTEIN

The idea that drugs of abuse yield reliable, direct, and generally positive emotional effects seems pervasive throughout most societies. Indeed, many people believe that drug abuse and addiction result from hedonistic desires run amok and that all individuals would surely find drugs rewarding were they not to exercise restraint in the face of such temptation (e.g., Measham, Aldridge, & Parker, 2001). Such a stance represents, then, an extreme form of the posi~ tive reinforcement view of drug abuse (see chap. 2, in this volume). A different, yet no less pervasive viewpoint holds that people who self~administer drugs do so, in great part, because drugs reliably reduce various manifestations of nega~ tive affect (see chap. I, this volume; Kassel et al., 2006); this particular notion reflects the negative reinforcement model of addiction. Hence, simply put, a pre~ dominant belief, persistent at the level of both society and science, is that drugs of abuse make people "feel" better, either by increasing positive affect or decreasing negative affect, and that such effects are inevitable. When the dust settles, however, problems emerge with both perspec~ tives, at least as portrayed in the rather extreme (and likely overly simplistic) Preparation of this chapter was supported in part by grants from the National Cancer Institute (1 PO 1CA98262) and from the National Institute on Alcohol Abuse and Alcoholism (5RO 1AA 12240-04 ).

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manifestations just presented. The reality appears to be that most, if not all, substances with any degree of abuse liability yield remarkably inconsistent effects on emotion, both across different people and within the same persons across time and situation (see Peele, 1985, for an in-depth discussion of these issues). Hence drugs as diverse as nicotine, alcohol, cocaine, and heroin may not be inherently pleasurable to all who try them (see, e.g., Eissenberg & Balster, 2000, who observed that most adolescents find their first cigarette aversive in numerous respects). Instead, context and other inter- and intrapersonal factors help shape and determine the affective consequences (both pleasant and unpleasant) of drug use (Zinberg, 1984). Acknowledging that myriad candidate variables may mediate or moderate the influence of drugs on affect, our intention for this chapter is to focus largely on one: cognition. It is clear that the past several decades have seen the emergence of cognitive theory in psychological research, with tremendous advances being made in the realm of cognitive and affective neuroscience (e.g., Lane & Nadel, 2002; Panksepp, 1998). As such, the field of psychopathology in general, and addiction science in particular, has benefited from a shift away from strict behavioristic accounts of behavior toward a realization of the profound role played by cognitive processes in promoting both adaptive and maladaptive behavior. Of particular relevance to the present chapter is that there is growing reason to believe that cognitive processes are intimately influenced by, and influence, emotional response. More specifically, then, in this chapter we review the theoretical and empirical literature positing that drug effects on emotion-in particular, alcohol and nicotine, because they have benefited from the most empirical scrutiny-may be mediated through cognitive processes. We begin with a discussion of the complex and reciprocal interplay between cognition and emotion. We then review the influential attention-allocation (alcohol myopia) model of alcohol reinforcement, with further consideration of how this perspective may also shed light on cigarette smoking's inconsistent effects on affect. Next, we review the extent to which alcohol may modify emotional experience through its impact on appraisal processes. Finally, we address the powerful role played by cognitive outcome expectancies in shaping (and being shaped by) the affective experience of drug use, and we make recommendations for future research.

COGNITION AND EMOTION: THEIR COMPLEX INTERPLAY AND IMPLICATIONS FOR SUBSTANCE ABUSE RESEARCH As discussed in the Introduction to this volume, clarifying one's use of the terms emotion (discrete feeling states), mood (more enduring feeling states, not attributable to a known precipitant), and affect (the most general term, encompassing both mood and emotion) is critical to sound theory building and test-

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ing. Hence, the extent to which one views cognition as integral to emotion ultimately depends on how broadly emotion is construed-as encompassing all evaluative experiences (affect, using our terminology) or only affective episodes with a distinct duration and object (emotion). Indeed, such distinctions among affect, mood, and emotion are not irrelevant to models of drug use (Kassel et aL, 2010). For example, Baker and colleagues' negative reinforcement model of drug addiction (Baker, Piper, McCarthy, Majeskie, & Fiore, 2004; see also chap. 1, this volume) distinguishes between processes that maintain drug use at low levels of negative affect, before conscious perception (e.g., during a negative mood), and the processes engaged by high levels of negative affect (e.g., during the experience of a negative emotion). Establishing whether a given affective experience is a mood or emotion is thus important for predicting which of these processes will motivate drug-taking behavior. T uming now to the construct of cognition, we begin with the idea that cognition cannot merely be identified with conscious thought. The belief that cognitive processing may have both automatic (unconscious, rapid, highcapacity, low-effort) and controlled (conscious, slow, limited-capacity, effortful) components is now generally accepted (Schneider & Shiffrin, 1977; Storbeck, Robinson, & McCourt, 2006). Furthermore, identification of cognition with cortical areas and of emotion with subcortical areas of the brain does not appear particularly accurate or useful with regard to current understanding of brain functionality (Duncan & Barrett, 2007; Moors, 2007). However, proposals linking specific emotions with well-delineated brain circuits (LeDoux, 2000; Panksepp, 2007) may be more successful at providing an anatomical distinction between emotions and cognition. Cognition may be viewed as any process that transforms input (Neisser, 1967). One perspective that may be particularly pertinent to the thesis of this chapter is the idea that cognition involves representation (Fodor & Pylyshyn, 1988; Moors, 2007). Hence, representations are considered necessary to explain any case in which the relationship between an input and output is neither invariant nor fixed. This definition also provides a convenient way of hypothesizing about the degree to which cognition contributes to the effects of particular drugs of abuse. For example, an understanding of direct drug effects on emotion (where they do exist) may not benefit at all by reference to said drug's cognitive effects. However, for drugs that have failed to demonstrate such predictable influences on emotion (in our view, the majority of drugs), cognition proves to be an important intervening variable (Kassel, 1997; Kassel, Stroud, & Paronis, 2003; Sayette, 1993; Steele & Josephs, 1988). Given the inconclusive state of the literature addressing the primacy of affect versus cognition, several possibilities for describing the relationship between these two constructs warrant consideration. LeDoux's (1995, 2000) work examining the role of the amygdala in conditioned fear offers a paradigmatic example of the independence stance. LeDoux (2000) identified two

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routes that may elicit fear: (a) a direct pathway from the thalamus that appears to bypass the sensory cortex, where semantic evaluations are made, inputting directly to the amygdala, which then coordinates changes in attention and fear responses; and (b) an indirect pathway passing through the sensory cortices that also inputs to the amygdala. The first pathway (frequently referred to as the low road) appears to represent an example of emotion elicitation with minimal involvement of cognition. Within this framework, cognition and emotion are held to represent qualitatively distinct phenomena, and LeDoux (1995) suggested that further research on the nature of the representations used in emotional (e.g., the amygdala) and cognitive (e.g., the hippocampus) areas of the brain may provide a principled basis on which to separate the two concepts. A similar model positing a greater variety of emotions was advanced by Izard (2007). This model proposes a number of basic emotion systems (interest, joy, happiness, sadness, anger, disgust, and fear) that are evoked by evolutionarily relevant stimuli with a minimum of cognitive mediation. Izard argued that these noncognitive basic emotions are most important in early development and in a limited number of evolutionarily significant situations. In adults, emotion-eliciting functions are usurped by emotion schema, which are more cognitively based. However, the basic emotion systems continue to provide the emotional tone or feeling across all experiences of affect, regardless of how experiences are evoked. Panksepp (2007) advanced a similar view but specified somewhat different basic affective systems (SEEK, RAGE, FEAR, LUST, CARE, PANIC, and PLAY, which are capitalized to indicate their usage as labels for neurological systems instead of lay terminology; see chap. 6, this volume). Finally, Russell (2003) proposed that "core affect" consists of two dimensions: (a) arousal and (b) valence. Core affect, then, is a technical term referring specifically to a basic neurophysiological state, not to the broader universe of terms indexed by affect. Implications of these various theories for research on drug-affect relationships become apparent. For example, one might expect some drugs to influence the low road (minimal cognitive involvement), whereas others may interfere with cognitively mediated fear. Indeed, the contrast between the specific reduction of fear-potentiated startle to unpleasant stimuli found with diazepam and the nonselective emotional effects of alcohol on startle reflects just such a separation (Patrick, Berthot, & Moore, 1996; Stritzke, Patrick, & Lang, 1995). Similarly, from Izard's (2007) perspective, another distinction of interest for substance use researchers might be differentiating drugs that influence basic emotion systems (and thus provoke unreflective emotional episodes) from those that alter factors relevant to emotion schemas. Finally, the distinction between core affect and basic emotions models may also be germane. If one adopts the core affect view, instruments that measure just two dimensions of valence and arousal may be sufficient to capture and distinguish drug effects (Russell, 2003). By contrast, the basic emotions view suggests that

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one might need to assess the specific actions of different drugs on separable neuropsychological systems (e.g., FEAR vs. SEEK; Panksepp, Knutson, & Burgdorf, 2002). Some theorists posit a stance (Lazarus, 1984; Moors, 2007) in which goal representations, or appraisals, are viewed as necessary for the elicitation of emotion. This approach to emotion-cognition relations has already yielded profitable contact with the substance abuse literature in the form of Sayette's ( 1993) appraisal~disruption theory of alcohol use (which we discuss later in this chapter). From the perspective of appraisal theory, the study of drug effects on emotion would necessarily involve understanding drug effects on cognitive processes. Hence, it is important to note that appraisal theorists concentrate on explaining discrete emotional episodes instead of all affective phenomena (e.g., evaluative preferences; Clore & Ortony, 2000; Lazarus, 1984). At the same time, some appraisal theorists acknowledge the possibility of noncognitive "moods" (Clore & Ortony, 2000), again suggesting that some drugs may affect moods instead of emotions per se, a potentially important and clinically meaningful distinction. Finally, some theorists believe that any division between cognition and emotion is fundamentally artificial (Barrett, Ochsner, & Gross, 2007; Duncan & Barrett, 2007; Leventhal & Scherer, 1987). According to this stance, cognition and emotion are neither neurologically nor onto logically distinct (Duncan & Barrett, 2007). These theorists instead emphasize a number of other distinctions. For example, Leventhal and Scherer (1987) preferred to think in terms of sensorimotor, schematic, and conceptual levels of processing. Thus, instead of separating cognitive and emotional effects, substance use researchers might instead define at which of these levels drugs are purportedly wielding their effects. Rotteveel and Phaf (2007) noted that positive affect may form a natural category with global processing, perceptual fluency, and other more traditionally cognitive phenomena with which it has more traits in common than with negative affect. Furthermore, Barrett et al. (2007) discarded the distinction of automatic versus controlled processing and instead proposed a constraint satisfaction system that may vary along the dimension of automaticity. In sum, each of these models offers new ways to view the effects of drugs on combined emotional-cognitive processes.

ALCOHOL MYOPIA A host of cognitive theories have been put forth to explain the mechanisms by which drugs affect emotions; however, within the realm of explicating alcohol's unreliable effects on emotional response probably no conceptualization has generated as much interest and empirical scrutiny as the attentionallocation model (Josephs & Steele, 1990; Steele & Josephs, 1988, 1990).

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Simply put, this conceptualization rests on the assumption that whereas alcohol does not possess an innate ability to assuage affective distress or increase positive affect, it does yield known and reliable effects on certain aspects of cognitive processing. Hence, it is argued that alcohol reduces psychological stress through its disruption of cognitive functioning. More specifically, then, alcohol is thought to both reduce cognitive processing capacity and restrict attention (by means of a reduction in cue utilization; cf. Easterbrook, 1959) to the most salient aspects of one's internal or external environment, resulting in alcohol myopia, "a state of shortsightedness in which superficially understood, immediate aspects of experience have a disproportionate influence on behavior and emotion, a state in which we can see the tree, albeit more dimly, but miss the forest altogether" (Steele & Josephs, 1990, p. 923). Although the model is applicable to understanding a diverse array of alcohol's effects on social behavior (e.g., drunken excess, drunken self-inflation, drunken relief of emotional distress), its stance regarding alcohol's effects on negative affect proves most pertinent to the present discussion. Indeed, Steele and Josephs's (1988, 1990) attention-allocation model has lent itself to examination of alcohol effects of alcohol on a variety of emotions, including anxiety and anger. According to this model, alcohol will affect anxiety indirectly through its reduction of cognitive capacity. Thus, when individuals are intoxicated and in the presence of benign distraction, they should experience a reduction in anxiety, through a reallocation of attention away from the stressful cognitions toward the distraction. However, in the absence of pleasant, engaging distraction, intoxicated individuals should actually experience an exacerbation of anxiety because their attention becomes focused on the cognitions that are, at least in part, promoting anxiety. A series of elegantly designed laboratory studies by Steele and Josephs (during which anxiety was induced in all participants by asking them to prepare a potentially embarrassing speech; e.g., Josephs & Steele, 1990; Steele & Josephs, 1988; Steele, Southwick, & Pagano, 1986) revealed that, in accordance with predictions of the model, alcohol significantly decreases anxiety when paired with benign distraction (rating pleasant art slides). However, when the anxious individual drinks in the absence of such distraction, alcohol reliably leads to an increase in anxiety. Hence, these studies provide some boundary conditions in which alcohol should-and should not-result in affective benefit. Recent work using psychophysiological measures of emotional response further supports the model and offers refinement of the operative mechanisms. For example, Curtin, Lang, Patrick, and Stritzke (1998) assessed fear response (by means of startle eyeblink magnitude) to threat of shock. The results revealed that, whereas alcohol attenuated overall startle reactivity, marked fear potentiation was observed in all conditions (alcohol and placebo) except when participants consumed alcohol in the presence of pleasant slides

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(Le., benign distraction). Correspondingly, Curtin, Patrick, Lang, Cacioppo, and Birbaumer (2001) found that, during intoxication, reduction in fear response (again assessed by startle eyeblink potentiation) occurred only with increased cognitive load (dual-stimulus conditions). Moreover, these reductions in fear response also coincided with reduced attentional processing of threat cues as evidenced by brain response assessed by P3 event-related potentials. Thus, dampening of stress response by alcohol appears to depend on participants' diminished ability to process competing cognitive demands, an interpretation consistent with the tenets of the attention-allocation model (see also Erblich & Earleywine, 1995). The attention-allocation model has also been used to explain alcohol's effects on aggressive behavior. It is thought that alcohol facilitates aggression in certain situations by decreasing attentional capacity and resulting in enhanced attentional focus on more salient hostile cues, relative to less pronounced cues promoting restraint. Indeed, research by Zeichner, Pihl, Niaura, and Zacchia (1982) revealed that whereas participants who consumed alcohol and partook in a laboratory aggression task displayed increased aggression when attending to the aggression task, they evidenced decreased aggressive behavior when they were distracted from the task. Giancola and Corman (2007) similarly found that moderate distraction suppressed aggression among participants who drank alcohol below that observed in participants who consumed a placebo beverage. Taken together, these results suggest--consistent with the findings observed with fear and anxiety-that alcohol can either increase or decrease aggressive responding depending on the presence or absence of competing attentional demands. As impressive as the findings are regarding the basic tenets of the attention-allocation model, limitations have been noted. For example, Sayette and others (e.g., Sayette, 1993; Sayette, Martin, Perrott, Wertz, & Hufford, 2001; Sayette, Smith, Breiner, & Wilson, 1992) have demonstrated that alcohol can reduce stress-responding even in the absence of distraction. In addition, although the attention-allocation model rests on the assumption that alcohol consumption reduces cognitive capacity, more recent research suggests that alcohol may actually impair the processing, rather than the capacity, component of attention (Saults, Cowan, Sher, & Moreno, 2007). Last, and as noted by Curtin et al. (1998), constructs such as salient and distracting stimuli bring with them potential for tautological inference (see Gilbert et al., 2008, for an interesting discussion of this issue). Thus, that which is viewed as more salient (when comparing stimuli competing for attentional primacy) can often be deemed so only after the fact (e.g., "I attended to the pleasant art slides because they were more salient" vs. "I attended to the stressful speech because that was more salient"). In this respect, clear a priori predictions steeped in sound theoretical rationale must be put forth in order to avoid such post hoc speculation.

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A TTENTIONAL MEDIATION OF CIGARETTE SMOKING'S EFFECTS ON EMOTIONAL RESPONSE On the basis of the belief that, like alcohol, nicotine has no direct effect on negative affect, Kassel (1997; Kassel & Shiffman, 1997) has proposed that smoking also affects anxiety and other emotional states indirectly, through its reliable effects on attentional narrowing (a notion that, although it differs slightly in its proposed mechanisms, is consistent with Gilbert's [1995] situation X trait adaptive response model). This is called the attentional mediation model. Drawing on Steele and Joseph's (1988) model of alcohol's effects on emotional response, Kassel (1997) noted that smoking similarly narrows the focus of attention and therefore may reduce anxiety by facilitating distraction from an impending threat. In the first test of this model, Kassel and Shiffman (1997) demonstrated that, as predicted, smoking reduced anxiety only when paired with a distractor (viewing and rating art slides). In the absence of benign distraction, smoking exerted no effect on anxiety. Among participants who were not exposed to the distractor, anxiety remained unchanged whether they smoked or not. Thus, the findings could not be explained by direct nicotine effects or nicotine withdrawal (because all smokers were minimally deprived, and a nonsmoker control group was also used). In a follow-up study (Kassel & Unrod, 2000), smokers smoked either a high-nicotine-yield (HN) or ultra-Iow-nicotine-yield cigarette with or without the presence of benign distraction. A similar pattern of findings emerged such that smokers who smoked the HN cigarette paired with art slides experienced a large reduction in subjective anxiety, whereas those who smoked the HN cigarette in the absence of distraction actually experienced a slight exacerbation of their anxiety. These findings, therefore, implicate nicotine as the agent in cigarette smoke responsible for attentionally mediated anxiety reduction. Moreover, the results from these studies point to the importance of considering context-in this case, benign distraction-when examining smoking's effects on emotional response (see also Gilbert & Welser, 1989; Gilbert et al., 2008). Although the attentional mediation model offers some promising initial findings, the extent to which the proposed mechanism is applicable to other negative affective states has yet to be determined. Neither is it clear whether the proposed mechanism is a volitional one, over which the smoker exerts conscious control, or instead is an automatic process of attentional capture (although Gilbert's attentional model [e.g., Gilbert et al., 2008] specifically asserts that nicotine biases attention toward positive cues and away from negative cues to the degree that these cues are of equal salience). Future research based on this kind of a contextual approach to the study of nicotinenegative affect interactions is clearly warranted.

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APPRAISAL DISRUPTION The appraisal-disruption model (Sayette, 1993) also invokes a cognitive perspective in trying to explain the inconsistent effects of alcohol on emotion. Appraisal is defined as the evaluation of the personal relevance of a situation and the implications of that situation for the person's well-being (Lazarus & Smith, 1988; Sayette, 1993). According to this theory, then, appraisals are presumed to be the primary mechanisms producing emotional responses (Lazarus & Smith, 1988). Sayette (1993) contended that alcohol interferes with appraisal by restricting priming, or the spread of activation, to related information stored in memory. If, during intoxication, a stimulus fails to trigger stored knowledge about how the stimulus is personally relevant, then appraisal will be disrupted and an emotional response less likely to occur. The bulk of research on the appraisal-disruption model has addressed the effect of alcohol on stress. However, the effects of alcohol on other emotions and the possibility of generalizing this model to other drugs of addiction also are briefly considered in this section. Regarding alcohol and anxiolysis, the primary prediction of the appraisaldisruption model is that alcohol will most effectively reduce stress when it is consumed before presentation of the stress-inducing stimulus. Under these conditions, intoxication will prevent both full appraisal of the noxious stimulus and activation of a stress response. In instances in which participants appraise a stressor while still sober, subsequent consumption of alcohol is not expected to reduce stress because the emotion-eliciting appraisals have already been made (Sayette, 1993). This prediction has been examined in several ways. First, a review of the literature (Sayette, 1993) revealed that stress reduction effects of alcohol were more common in studies that stressed participants subsequent to intoxication. Second, several experimental studies that directly manipulated the temporal patterning of drink and stressor have produced results supportive ofthis model (Noel, Lisman, Schare, & Maisto, 1992; Sayette & Wilson, 1991; Sayette, Wilson, & Carpenter, 1989). Finally, at least one preliminary investigation of the effects of alcohol on construal of threatening events in the real world-specifically, the emotional reactions of rape victims who were or were not under the influence of alcohol at the time of their trauma-supported the tenets of this model (Clum, Nishith, & Calhoun, 2002). Findings from several other studies also shed light on predictions derived from the appraisal-disruption model and, in doing so, raise additional questions. First, one study that directly manipulated temporal order (alcohol vs. stressor) confirmed the predictions of appraisal theory, but only for men with high anxiety sensitivity. Of interest is that females high in anxiety sensitivity, and all participants low in anxiety sensitivity, demonstrated an opposite pattern, with consumption of alcohol prior to stressor onset actually increasing anxiety (Zack, Poulos, Aramakis, Khamba, & MacLeod, 2007).

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Second, to date, it has been difficult to confirm (and empirically assess) the proposed mechanisms underlying appraisal disruption. The model differs from others purporting to explain drug effects on emotion in that impairment of both automatic and controlled processes is thought to necessarily contribute to inadequate appraisaL (Other theories, such as attention allocation, tend to emphasize the impairment of controlled processes only; Sayette, 1999.) Indeed, impairment of the automatic processes governing priming is viewed as the major operative mechanism (Kirchner & Sayette, 2003; Sayette, 1993). Nonetheless, it has been difficult to gamer evidence directly supporting impairment of automatic processes by alcohol. Studies that have examined alcohol-induced impairment of explicit and implicit memory processes have typically revealed intact implicit memory (Hashtroudi, Parker, Delisi, Wyatt, & Mutter, 1984; Kirchner & Sayette, 2003). Kirchner and Sayette (2003) argued that the more pertinent distinction may not be automatic versus controlled processes but instead perceptual versus conceptual features, with stimulus-driven perceptual processing left intact and conceptual processing impaired by alcohol. Indeed, alternate measures of priming not dependent on perceptual processing have found that intoxication constrained the spread of priming (at least for participants without a family history of alcoholism; Sayette, Martin, Perrott, & Wertz, 2001) and reduced interference on an emotional Stroop task presumed to index the degree of automatic activation of negative words (Sayette, Martin, Perrott, et aL, 2001). Furthermore, studies of information retrieval during intoxication have demonstrated reduced retrieval of negative information during intoxication (Fromme, D'Amico, & Katz, 1999; Sayette, 1994). These findings are supportive of constrained priming by alcohol, providing one assumes that positive information is more easily primed for the typical nondepressed individuaL Regardless of whether the primary impairment is in automatic priming processes or more controlled processes, alcohol has been shown to reliably interfere with the elaboration and encoding of new material into memory, consistent with the proposed disruption of memory and appraisaL Following from the notion that positive associations may be more difficult to disrupt than negative associations, the appraisal-disruption model also offers differential predictions for alcohol's effects on different emotions. Appraisal is viewed as integral in producing all emotions, and thus one might expect reduced overall emotional responding-to both pleasant and unpleasant stimuli-during intoxication (as was observed when psychophysiological measures of emotion were used; Stritzke et aI., 1995). However, the idea that some appraisals may be more resistant to disruption than others actually leads to prediction of specific disruption of negative associations and emotions (as found in Fromme et aI., 1999; Sayette, 1994). Furthermore, one meta-analysis demonstrated that the suppression of anxiety by alcohol can produce a complementary effect of disinhibition of aggression (Ito, Miller, & Pollock, 1996).

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Whereas this failure of alcohol to suppress anger might suggest that the retrieval of both positive and anger-related information is more difficult to disrupt than the retrieval of anxiety-related information, this explanation awaits further empirical scrutiny. Several other implications of appraisal theory are worthy of consideration. The comorbidity of anxiety disorders and alcohol abuse might lead one to predict that anxious individuals would derive the most benefit from appraisal disruption (Gerlach, Schiller, Wild, & Rist, 2006); however, as noted earlier, this theory predicts that certain appraisals will be more difficult to disrupt than others. Although one would expect that in individuals who do not have anxiety disorders positive associations will be more practiced and thus more resistant to the effects of alcohol, one might anticipate that chronically anxious individuals may instead have highly practiced and integrated negative associations, which would be more resistant to disruption. Consistent with this idea, one study found that control participants, but not participants with social phobia, experienced anxiolysis when alcohol was administered prior to stressor onset (Gerlach et al., 2006). It also seems reasonable to propose that, on the basis of the basic precepts of appraisal theory, individuals who are already cognitively impaired will derive the most anxiolytic benefit from alcohol, a prediction supported by several studies (e.g., Peterson, Finn, & Pihl, 1992; Sher & Walitzer, 1986). On the other hand, one might also posit that individuals with enhanced cognitive abilities would derive heightened benefit from the appraisal-disruption effects of alcohol (reflecting a variation of the law of initial values hypothesis, which states that the better a person's ability to initially appraise information, the more emotional benefit he or she will derive from the disruptive effects of alcohol). In fact, findings consistent with this notion have been reported as well (Sher, Bartholow, Peuser, Erickson, & Wood, 2007). Finally, the potential applicability of the appraisal-disruption model to other drugs of abuse ultimately depends on the extent to which such drugs exert similar effects on cognitive processes. Of interest is that one investigation of nicotine found effects opposite in direction to those predicted for alcohol: An increased stress response was observed when the stressor was presented after, rather than before, cigarette smoking (Juliano & Brandon, 2002). Such a finding likely reflects inherent differences in smoking's (nicotine's) effects on cognitive processing relative to alcohol. Indeed, in this respect there is reason to believe that although both drugs may share a propensity to induce attentional narrowing, alcohol reduces overall attentional processing capacity, whereas nicotine appears to increase it (Kassel, 1997). In sum, the appraisal-disruption model is an exemplar of theoretically based research that, drawing on cognitive mechanisms, challenges the notion that alcohol has direct effects on emotional outcomes. The research generated to date that has assessed the tenets of this approach has been compelling

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and continues to offer exciting possibilities with respect to better understanding drug effects on emotional response systems.

DRUG OUTCOME EXPECTANCIES A growing body of research has revealed that individuals' actual experiences of a drug (e.g., affective responses) are both shaped by, and subsequently shape, the outcome expectancies held for that drug. Commonly defined as an individual's beliefs about the probable consequences associated with use of a particular substance, drug outcome expectancies are associated with substance use behaviors in important and meaningful ways. More specifically, burgeoning evidence collectively implicates drug expectancies in all critical periods of the drug use trajectory, from initiation through relapse. Results yielded by prospective studies have identified expectancies as causally related to initiation and maintenance of alcohol (Goldman, Del Boca, & Darkes, 1999; Jones, Corbin, & Fromme, 2001) and tobacco (Brandon, Juliano, & Copeland, 1999) use. Furthermore, drug expectancies are capable of distinguishing among classes of substance users (e.g., alcoholics, problem drinkers, nonproblem drinkers; Connors, O'Farrell, Cutter, & Thompson, 1986). Several theories offer insight into the processes by which drug outcome expectancies are acquired and shaped across the life span. Social learning theory (Bandura, 1977) espouses that an individualleams what to expect from the use of a drug by observing the actions modeled by others (Abrams & N iaura, 1987). There is also evidence to suggest that expectancies are derived from social messages delivered through various media outlets (e.g., Connolly, Casswell, Zhang, & Silva, 1994). Moreover, such findings suggest that drug expectancies may develop at a young age, independent of direct pharmacological experience. Indeed, children of preschool and elementary school age hold both positive and negative expectancies for alcohol use, even in the absence of having ever consumed alcohol (e.g., Dunn & Goldman, 1996; Zucker, Kincaid, Fitzgerald, & Bingham, 1996). Conditioning theories suggest that expectancies are shaped by repeated experiences of positive (e.g., Glautier, 2004) and negative (e.g., Baker et aL, 2004) reinforcement such that use of a substance is paired with an emotionally rewarding consequence. Hence, as experience with a drug increases, so does the strength of the associative links (memory nodes) between substance use and expected affective change in one's schematic representation of a particular drug. More specifically, cognitive schemas provide the framework in which we organize knowledge about substance use as well as expectations for how substance use affects behavior and emotion. Following this logic, the decision to use a substance should be predominantly driven by the ease in which these associations are activated and accessed in memory.

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Although positive expectancy outcomes generally predict amount and frequency of substance use (e.g., Brown, 1993), a specific subset of affectively laden expectancies have demonstrated unique contributions in explaining drug use behaviors. Considerable evidence suggests that expectancies for negative affect amelioration, in particular, are related to more problematic substance use outcomes (Cooper, 1994; Farber, Khavari, & Douglas, 1980). For example, tension-reduction expectancies predict problem drinking in college students (Brown, 1985) and current alcohol dependence in young adults (Kilbey, Downey, & Breslau, 1998). Furthermore, Wetter et al. (1994) found that negative (i.e., negative affect reduction), but not positive, reinforcement expectancies predicted cessation outcomes among smokers. It is important to note that expectations for negative affect and tension reduction have been repeatedly implicated in relapse to drinking and smoking (e.g., Marlatt, 1985; Shiffman, 1984). Expectations for enhancement (e.g., mood improvement, increased sociability) have also been implicated in substance use behaviors. For instance, Bauman and Chenoweth (1984) found that changes in smoking among teenagers (including smoking initiation among prior nonsmokers) was best predicted by expectations of deriving pleasure from smoking. Cooper, Russell, Skinner, and Windle (1992) found that enhancement and coping motives, although conceptually different from expectancies, differed in the magnitude of their effects on drinking behavior such that enhancement, but not coping, motives were associated with heavy frequent drinking. In sum, then, expectancy networks appear to be intricately intertwined with human affective processes (Goldman et al., 1999). Broadly construed, drug outcome expectancies are thought to exist at both implicit and explicit levels. Some scholars have speculated that as experience with a substance mounts, explicit awareness of expectancies decreases, supplanted by more automaticity in behavior; that is, in the presence of drug schema activation expectancies come to influence behavior and outcomes implicitly, in the absence of conscious deliberation (see Tiffany, 1990). Assessment of explicit outcome expectancies requires effortful introspection by the individual and is commonly captured with self-report questionnaires. Implicit outcome expectancies, in contrast, are thought to be shaped by both early drug experiences and behaviors that influence affective experience. Thus, such implicit expectancies appear to mediate drug use behavior in an automatic fashion (Thush & Wiers, 2007). A number of empirically supported proxies, introduced by cognitive psychologists, are available for determining the effect of implicit drug expectancies on affective outcomes in the laboratory. Memory association tasks are frequently used for this purpose because accessibility of expectancies is likely dictated by the strength of connections among drug stimuli, drug-related contexts, and outcome expectancies stored in memory. In turn, degree of expectancy accessibility is related to drug use behaviors {Goldman et al.,

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1999; Leigh & Stacy, 1998; Palfai & Wood, 2001; Stacy, 1997). As such, several methods for implicit priming of expectancies have been established (e.g., implicit-association tests, exposure to drug-related advertisements). For instance, reaction time (e.g., time needed to identify drug-related stimuli) should be faster (i.e., performance enhanced) in tasks that prime drug-related concepts. Free-association paradigms are also commonly used to gauge drug expectancy accessibility on activation of expectancy network structures through priming. To partition the respective contribution of expectancies and direct drug effects, numerous controlled laboratory studies have used placebo control designs (Marlatt & Rohsenow, 1973). Comprehensive reviews of such studies indicate that drug expectancies exert significant influence over actual consumption patterns and behavioral and affective change (Brandon et al., 1999; Goldman et al., 1999). In an effort to increase ecological validity, laboratory studies have also considered the role of contextual influences in the relationship between substance use and affective change. Drug outcome expectancies, although traitlike and stable in many ways (e.g., alcohol; Brown, Christiansen, & Goldman, 1987), are also thought to differ across context, a term that, broadly construed, encompasses environmental (e.g., individual vs. group [Sher, 1985], naturalistic bar vs. laboratory [Wall, McKee, Hinson, & Goldstein, 2001]), cognitive (e.g., accessibility of drug-related information, Earleywine, 1995), physical (e.g., withdrawal, craving, Gottlieb, Killen, Marlatt, & Taylor, 1987; Tate et al., 1994), and affective states (e.g., mood; Hufford, 2001; Read & Curtin, 2007). Manipulation of these situational variables has proven to be a particularly effective means of determining their contribution to the relationship between drug expectancy and affective outcomes. Regarding the processing of cognitive-affective drug expectancies, the principle of encoding specificity (Tulving, 1983) posits that information about the effects of a particular drug is more readily accessible when one is exposed to cues (i.e., mood states) similar to those present when expectancies were initially formed. In accordance with this notion, the situational specificity hypothesis espouses that contextual variation in substance use behavior is driven by exposure to cues previously associated with substance use (i.e., mood-congruent memory; Blaney, 1986). Because experiences with substances are often affectively laden and motivated, it is likely that an affective state may trigger activation of affective outcome expectancies and influence how those expectancies are cognitively processed. For example, Hufford (2001) found that negative affect was positively correlated with positive expectancies for alcohol and that participants in a negative mood induction condition endorsed more positive alcohol expectancies relative to participants who had been assigned to a positive mood induction. Correspondingly, McKee, Wall, Hinson, Goldstein, and Bissonnette (2003) observed that in response to negative mood induction, participants were more likely to generate smoking expectancies about the nega-

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tively reinforcing properties of smoking (i.e., negative affect relief). Taken together, these findings highlight the potential risk for state negative affect, in particular, to produce substance use behaviors as a function of affective coping expectancies. In sum, the importance of affective expectancies in drugs' influence on emotion cannot be overstated. Furthermore, to the extent that these expectancies are malleable, prevention initiatives should attempt to modify expectancies using cognitive restructuring techniques (e.g., Cruz & Dunn, 2003), and treatment providers should be aware of the contribution made by expectancies to risk for relapse (see chap. 11, this volume). Last, although this chapter has focused its discussion of expectancies primarily on nicotine and alcohol, we believe that the theoretical richness of these models makes them ideal for the study of psychological mechanisms subserving other drugs of abuse.

CONCLUSIONS Steeped in the observation that many drugs exert their effects on emotion indirectly, we reviewed the literature showing that cognitive factors can, and likely do, playa critical role in shaping affective responses to drugs. (At the same time, we are quick to recognize that many other inter- and intrapersonal factors also contribute to drug effects on emotion.) Taken as a whole, then, this area of research has provided rich theoretical frameworks for understanding the variable effects of drugs such as alcohol and nicotine on behaviors and emotional states, including fear, anxiety, and aggression. Moreover, in several instances these models have described the boundary conditions under which drugs will-and will not-lead to negative reinforcement through reduction in anxiety and/or fear. As such, this burgeoning area of research has done much to advance the field's understanding of the mechanisms underlying addictive behavior. Where should we go from here? Certainly, the clinical implications of the approaches to understanding drug-affect associations are rife with potential. As noted earlier, the use of strategies by which one's drug outcome expectancies are challenged (e.g., "Alcohol always makes me happy") coupled with recognition and acceptance of negative outcomes (e.g., "I often miss classes the day after drinking") offers promising avenues for treatment. Indeed, Cruz and Dunn (2003) offered an impressive exemplar of such an approach. Targeting fourth-graders, they used an alcohol-expectancy challenge approach, revealing that subsequent to this intervention children exhibited a greater likelihood to associate alcohol use with negative and sedating consequences and a decreased likelihood to associate alcohol with positive and arousing consequences. On the basis of the observation that children and adults who emphasize negative and sedating effects are less likely to use alcohol,

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expectancy challenge interventions that have been successful at modifying expectancies and subsequently decreasing alcohol consumption of adults may be useful in reducing the likelihood of early alcohol use among children (Dunn, Lau, & Cruz, 2000). The tools now available from the realms of cognitive and affective science to addiction researchers need to be used to advance our understanding of the reinforcing mechanisms governing drugs of abuse. Although tremendous advances have been made in this area over the past decade, more research of this nature is sorely needed. Well-articulated, theoretically based approaches to the study of drug effects on emotion that consider the complex interplay of cognition and emotion will no doubt ultimately inform intervention and prevention alike and help stem the tide of such destructive behavior.

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4 DRUG CRAVING AND AFFECT STEPHEN T. TIFFANY

Craving is a core feature of drug addiction. It emerges early in the natural history of drug abuse disorders (e.g., O'Loughlin et al., 2003) and is experienced by the vast majority of drug-dependent individuals. For example, over 90% of daily cigarette smokers report having at least some craving when they have not smoked for a few hours (Tiffany, Warthen, & Goedeker, 2009). Clinicians who work with addicts know that craving is a central concern for their clients. Addicts worry and complain about craving while they are using, as they try to stop using, and even long after they have quit using drugs (Tiffany, 1990; Tiffany et al., 2009). Given the ubiquity and salience of craving in addictive disorders, it should be no surprise that there has been extensive research on craving. Indeed, craving research has exploded over the past 20 years, increasing 50-fold compared with the preceding 20 years (Tiffany et al., 2009). More recently, in the first half of the present decade (2001-2006) there have been more than 2,100 published research articles with the words crave or craving in their abstracts. This research includes studies on the assessment, prevalence, correlates, manipulation, neurobiology, conceptualization, and treatment of craving in both humans and animals. Craving unquestionably remains a major issue for addicts and researchers alike, with most convinced that a

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deeper understanding of the sources and functions of craving in addiction will almost certainly lead to major advances in our ability to effectively treat addictive behavior. Affect, like craving, has also figured prominently in research on addiction. As evidenced by the chapters in this book, affective processes have been implicated as major causes, consequences, and correlates of drug abuse and dependence from the onset of scientific studies of addiction. Accordingly, research and theorizing on craving have often addressed affective processes. Many of the manipulations that influence affect have an impact on craving levels; conversely, procedures that trigger craving typically influence affective variables. More generally, craving typically has some emotional tone-most often negatively valenced, although occasionally positive. Furthermore, many theories of craving, specifically, and drug addiction, more broadly, invoke affective processes as contributing to the generation and maintenance of addictive behavior. There are also several theories of craving that, although not overtly using affective process as integral mechanisms, have clearly assimilated concepts derived from the literature on affect. Finally, many of the conceptual and empirical conundrums that confront craving research have similarly bedeviled our understanding of affective processes. In sum, it is nearly impossible to comprehensively review research on craving without also addressing what is known about craving's affective associates. In this chapter, I present major findings and concepts in the craving literature as they relate to affective processes. I start with an overview of how craving is typically assessed and manipulated and then summarize some primary facts regarding what we know about craving. This is followed by a selected presentation of major theories of craving, with a focus on models that deal explicitly with affect as a major component, input, or output of hypothesized craving processes. Next, I present a summary of research that addresses what we know about relationships between craving and affect. I conclude the chapter with a consideration of some of the major issues confronting research on craving, issues that have similarly challenged research on affect. In the last section, I provide some recommendations for future studies of affect-craving relationships-research informed, in part, by theoretical and empirical advances in the affective domain.

MEASUREMENT AND MANIPULATION OF eRAVING Two major methodological developments have had a major impact on modem craving research. First, the measurement of self-reported craving has advanced considerably over the past 20 years with the development of multiitem questionnaires that are highly reliable and very sensitive to fluctuations in craving over time (e.g., Florsheim et al., 2007; Heishman, Singelton, & Liguori, 2001; Tiffany & Drobes, 1991; Tiffany, Fields, Singleton, Haertzen,

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& Henningfield, 1995; Tiffany, Singleton, Haertzen, & Henningfield, 1993). The items on these questionnaires typically include ratings of statements of desire for a specific drug (e.g., "I have an urge for cocaine") but may cover other semantic content, including statements of intent and plans to use (e.g., "I will smoke as soon as possible"), anticipation of specific outcomes from drug use (e.g., "I would feel less depressed ifl could drink now"), and difficulty controlling use (e.g., "It would be difficult to turn down a joint right this minute"). Factor analyses of these questionnaires generally reveal that the latent structure of the items is multidimensional, with two or more first-order factors and a single higher order or general craving factor that permeates the craving questionnaire. The presence of a general craving factor across these various instruments has led to the development and widespread use of short-form craving questionnaires that reliably measure general levels of drug-specific craving in research settings (e.g., Cox, Tiffany, & Christen, 2001). Second, craving research has also advanced substantially by the widespread adoption of cue-reactivity procedures to study craving processes under controlled laboratory conditions (Carter & Tiffany, 1999; Drummond, Tiffany, Glautier, & Remington, 1995). The cue-reactivity paradigm draws on the common observation that craving is readily triggered when addicts are presented with stimuli that are strongly associated with previous episodes of drug use (Drummond et al., 1995). People with alcohol dependence, for example, will say that encounters with particular cues and situations, such as a drinking friend, a bottle of alcohol, or remembering past drinking episodes, can easily induce craving (Ludwig, 1986). Similarly, nearly all regular cigarette smokers will describe scenarios-the sight or smell of a lit cigarette, the end of meal, a break at work-that readily generate craving. Cue-induced craving is so commonly observed across addictive disorders that nearly all contemporary theories of addiction invoke cue-specific processes to explain craving and drug use (Tiffany et a1., 2009).

eRAVING FUNDAMENTALS After 25 years and across thousands of research articles, we can identify key factors that influence craving. These include drug abstinence, drug priming, environmental cues, and availability of drug use. Drug Abstinence

One surefire way of generating craving in an addict is to deny that person access to drugs. Drug abstinence or withdrawal reliably leads to increased craving in alcohol, nicotine, opiate, and stimulant addicts (e.g., Greenwald,

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2005; McGregor et al., 2005; Schuh & Stitzer, 1995; Schuster, Greenwald, Johanson, & Heishman, 1995; Tiffany & Drobes, 1991). In the case of some drug-dependence disorders, most notably daily cigarette smokers, craving can be elevated within a relatively short period after the last exposure to drug. For example, regular cigarette smokers can show a significant increase in craving after only 30 minutes of abstinence (Schuh & Stitzer, 1995). Over days or weeks of continued abstinence, craving tends to dissipate, although some addicts may report experiencing bouts of craving months or years after their last drug use (Tiffany, 1990). Drug Priming

Just as removal of a drug can evoke craving, so too can presentation of a drug. For example, an intravenous infusion of a small dose of cocaine to a cocaine addict can produce a transient increase in cocaine craving (e.g., Jaffe, Cascella, Kumor, & Sherar, 1989). This phenomenon, called drug-primed craving (de Wit, 1996; see chap. 2, this volume), has been studied most extensively in cocaine users (Mahoney, Kalechstein, De La Garza, & Newton, 2007) but has also been reported with heroin addicts (e.g., Meyer & Mirin, 1979) and alcoholics (e.g., Hodgson, Rankin, & Stockwell, 1979). In some instances of drug-primed craving it is difficult to isolate the pharmacological effects of drug exposure from exteroceptive cues that accompany drugs given through standard routes of administration. So, for instance, a sip of alcohol presents the user with both pharmacological (i.e., ethanol) and exteroceptive (e.g., taste) stimuli. Unless the two types of cues are experimentally dissociated, increases in craving following presentations of alcohol cannot be unambiguously attributed to the pharmacological effects of the drug. Environmental Cues The assumption underlying the cue-reactivity paradigm is that the presentation of drug cues will activate motivational processes that regulate approach and consumption of the associated drug (Drummond et al., 1995). Cues that have commonly been used in cue-reactivity research include mental imagery (e.g., imagining drug use scenarios), visual cues (e.g., pictures or videos of drug use), auditory cues (e.g., tape-recording of a drug scenario), and in vivo cues (e.g., holding a cigarette). Common reactivity measures have included selfreport measures (e.g., craving and mood), physiological measures (e.g., heart rate, functional magnetic resonance imaging activation), and behavioral measures (e.g., drug-seeking, drug consumption). The cue-reactivity paradigm, which has been applied to every major type of drug abuse disorder, has become the principal method for examining craving and drug motivational processes in the drug abuse field.

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Researchers have systematically developed several different procedures for the manipulation of craving to smoke in the laboratory (Burton & Tiffany, 1997; Cepeda Benito & Tiffany, 1996; Conklin & Tiffany, 2001; Conklin, Tiffany, & Vrana, 2000; Drobes & Tiffany, 1997; Elash, Tiffany, & Vrana, 1995; Maude-Griffin & Tiffany, 1996; Tiffany & Drobes, 1990; Tiffany & Hakenewerth, 1991; Tiffany, Cox, & Elash, 2000). Across all of this research, cigarette smokers report substantially stronger craving following presentation of smoking cues relative to nonsmoking cues. As one example, my colleagues and I have directly compared cue reactivity to smoking stimuli when those stimuli were presented through either in vivo or imaginal modes (Burton & Tiffany, 1997; Drobes & Tiffany, 1997; Tiffany et al., 2000). Drobes and Tiffany (1997) had smokers imagine scenarios that described smoking and craving situations or were smoking neutral (6 trials, 3 of each type). In addition, participants were given in vivo cue trials during which they watched an experimenter light and smoke a cigarette or pour and drink water (6 trials, 3 of each type). The 12 trials were presented in a randomized order to each smoker. Figure 4.1 shows the craving results from the reactivity session for 100 smokers. Cigarette trials of both types produced substantially stronger

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Figure 4.1. The impact of smoking-related cues (imaginal and in vivo) on craving. Data are from Drobes and Tiffany (1997). N = 100. QSU-Brief = Questionnaire on Smoking Urges-Brief.

DRUG CRAVING AND AFFECT

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craving than neutral trials, but the magnitude of craving was not influenced by the mode of stimulus presentation (in vivo or imaginal). The cue-reactivity effects routinely observed in studies of cigarette smokers are typical in the cue-reactivity literature. A meta-analysis of more than 40 cue-reactivity studies with cigarette smokers, alcoholics, heroin addicts, and cocaine addicts showed that craving and auronomic reactions can display a great deal of cue specificity (Carter & Tiffany, 1999). On average, drug-cue presentations produced significant increases in heart rate and sweat gland activity and significant declines in skin temperature. With the exception of studies on alcoholics, cue-specific craving across groups was extremely robust, producing average effect sizes in excess of 1.20. Overall, the craving effects were substantially larger than effects observed with the autonomic measures; these latter effects were, on average, smalL Drug Availability

One factor that may influence the magnitude of cue reactivity is the extent to which addicts believe that they will be able to use drugs either during or immediately after a session of cue exposure (Carter & Tiffany, 2001; Wertz & Sayette, 2001). Studies in which participants are informed that they will or will not be able to use their drug at the completion of the experimental session (distal availability) tend to produce only modest effects on cue-specific craving (see Carter & Tiffany, 2001, for a review). In contrast, availability can be manipulated by informing addicts that they would have immediate access to drug use in the presence of drug cues. One may suppose that the extent to which the participant has immediate drug access (local availability) might have a different impact on cue reactions than the situation in which access was permitted at the end of a session (distal availability). Carter and Tiffany (2001) studied the impact of local availability on responses to drug cues by modifying the conventional cue-reactivity design. In their cue-availability paradigm, availability was manipulated on each trial by presenting smokers with either a glass of water or a lit cigarette behind a glass door and informing them of the probability (0%, 50%, or 100%) that they would be able to open the door at the end of the exposure trial and sample the cue. The door was locked or unlocked depending on the probability given at the beginning of the triaL If the door was unlocked, the smoker could take one puff of the cigarette on cigarette trials and one sip of water on the water trials. Craving and physiological measures were collected in the presence of the cues. Smokers reported higher craving on cigarette trials than on water trials, and this difference increased with the probability of gaining access to the cigarette (see Figure 4.2). The smokers also had higher levels of skin conductance on cigarette trials, and this difference was most pronounced when they

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Affective Content Figure 4.3. Mood (top panel) and craving (bottom panel) ratings as a function of urge and mood content of imagery material in cigarette smokers. Data are from Maude-Griffin and Tiffany (1996). N = 60.

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STEPHEN T. TIFFANY

decreased positive mood report and increased negative mood report to positive affect and negative affect scripts. The bottom panel of Figure 4.3 shows the craving ratings generated by the imagery manipulation. Overall, inclusion of explicit smoking and craving material in the imagery scripts elevated craving relative to the comparable control scripts. For example, both positive and negative affect scripts with urge content generated substantially stronger craving ratings than the positive and neutral affect scripts without urge descriptors. The data also yielded clear evidence that induction of negative mood elevated craving: Imagery of negative affect scripts with no urge content produced substantially stronger craving to smoke than no-urge positive and negative affect scripts. In contrast, the induction of positive affect by itself had no significant impact on craving levels. The addiction literature is replete with examples of the impact of manipulations of negative affect and stress on craving. Laboratory procedures that induce negative affect consistently trigger craving in alcoholics (e.g., Cooney, Litt, Morse, Bauer, & Gaupp, 1997; Fox, Bergquist, Hong, & Sinha, 2007), cigarette smokers (e.g., Conklin & Perkins, 2005; Maude-Griffin & Tiffany, 1996; Perkins & Grobe, 1992; Tiffany & Drobes, 1990), and cocaine addicts (e.g., Sinha, Fuse, Aubin, & O'Malley, 2000; Sinha, Garcia, Paliwal, Kreek, & Rounsaville, 2006). In contrast, research to date has not produced evidence that induction of positive affect increases craving (Conklin & Perkins, 2005; Maude-Griffin & Tiffany, 1996; Tiffany & Drobes, 1990). Impact of Craving Manipulations on Affect With conventional cue-reactivity studies, when affect is included as an outcome variable presentations of stimuli that induce craving tend to generate negative affect and/or attenuate positive affect. In our laboratory, my colleagues and I have developed multiple procedures for smoking cue presentations to cigarette smokers, including long-imagery narratives, brief-imagery presentations,

and combined imagery-in vivo presentations (see Tiffany et al., 2009, for a review). Across all of these procedures, presentations of smoking-related cues consistently generate increases in negative mood ratings and/or decreases in positive mood ratings. Other researchers have reported similar profiles of mood outcomes in cue-reactivity studies with alcoholics (e.g., Fox et al., 2007), cocaine addicts (e.g., Harris, Batki, & Berger, 2004; Saladin, Brady, Graap, & Rothbaum, 2006), and heroin addicts (e.g., Yu et al., 2007). The literature on the affective consequences of drug-primed craving is not as clear cut as the cue-reactivity literature. In the most comprehensive report on the affective consequences of cocaine priming, Johnson and colleagues (Johnson, Roache, Ait-Daoud, Wells, & Mauldin, 2004) administered low or high intravenous doses of cocaine in a placebo-controlled design

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and measured craving and affective outcomes with the Profile of Mood States (McNair, Lorr, & Droppleman, 1971). Cocaine significantly increased selfreported craving and scores on the Tension-Anxiety scale of the Profile of Mood States. In addition, cocaine was associated with a significant increase in reported euphoria defined by an aggregated rating of "high," "like [the] effect," "rush or thrill," "aroused or stimulated," and "mind [is] racing." Comparable cocaine-induced euphorigenic effects assessed with similar descriptors have been found in other studies (e.g., Donny, Bigelow, & Walsh, 2004). The extent to which these items reflect positive affective states or a nonaffective, drug-specific subjective condition is unclear because the affective correlates of measures of drug euphoria have not been systematically examined to date. The affective consequences of craving manipulations might be revealed by measures other than self-report measures of affect. For example, the startle response to an abrupt, high-intensity stimulus has been studied extensively as a nonverbal index of basic affective propensities. Many studies (e.g., Bradley, Cuthbert, & Lang, 1999; Cook, Davis, Hawk, Spence, & Gautier, 1992; Vrana, Spence, & Lang, 1988) have shown that startle responding-for example, eyeblink-is amplified when the startle stimulus is presented in the context of aversive stimuli (e.g., photos depicting gruesome scenes) and attenuated when the same stimulus is presented in the context of affectively positive stimuli (e.g., photos of sleeping babies). Elash et al. (1995) reported that startle eyeblink responding was amplified when smokers imagined brief vignettes that described cigarette craving relative to imagery of neutral vignettes. This outcome was interpreted as indicating that the craving-inducing imagery activated a primarily aversive, affectively negative state. Subsequent research using startle as an index of the affective substrates of cue reactivity has produced mixed outcomes. Some researchers have reported that presentations of drug-related photos attenuated startle responses relative to neutral photos in smokers (Cinciripini et al., 2006) and alcoholics (Mucha, Geier, Stuhlinger, & MundIe, 2000), whereas others have not replicated these effects (e.g., Franken, Hulstijn, & Starn, 2004; Geier, Mucha, & Pauli, 2000; Mueller, Mucha, & Pauli, 1998). Given the decidedly mixed record of the startle paradigm across these studies, the probative value of this measure as a direct readout of the affective substrate of cue reactivity has yet to be established. Correlations of Craving and Affect An evaluation of the correlations of craving measures with measures of affect and mood should reveal the essential affective tone of craving processes. With that in mind, Table 4.1 depicts the correlations of major multi-item measures of craving for cigarettes, cocaine, alcohol, and heroin with the Pos-

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TABLE 4.1 Correlations of Craving and Mood Drug

N

Measure

p

Nicotine (cigarette)

230

Questionnaire on Smoking Urges -.216 Positive mood" .307 Negative mood b

Cocaine

225

Cocaine Craving Questionnaire-Now