Dispelling the Myths about Addiction

Strategies to Increase Understanding and Strengthen Research

Committee to Identify Strategies to Raise the Profile of Substance Abuse and Alcoholism Research

Division of Neuroscience and Behavioral Health

Division of Health Promotion and Disease Prevention

INSTITUTE OF MEDICINE

NATIONAL ACADEMY PRESS
Washington, D.C.
1997



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Dispelling the Myths about Addiction Strategies to Increase Understanding and Strengthen Research Committee to Identify Strategies to Raise the Profile of Substance Abuse and Alcoholism Research Division of Neuroscience and Behavioral Health Division of Health Promotion and Disease Prevention INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1997

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NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. This study was supported under a grant from the W.M. Keck Foundation of Los Angeles. The views presented are those of the Institute of Medicine Committee to Identify Strategies to Raise the Profile of Substance Abuse and Alcoholism Research and are not necessarily those of the funding organization. Library of Congress Catalog Card No. 97-69691 International Standard Book Number 0-309-06401-5 Additional copies of this report are available from: National Academy Press 2101 Constitution Avenue, N.W. Lock Box 285 Washington, DC 20055 Call 800-624-6242 or 202-334-3313 (in the Washington metropolitan area) or visit the National Academy Press's online bookstore at http://www.nap.edu. Copyright 1997 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin. Cover: The cover of this report includes a circular motif, called a mandala, that was designed by Leigh Coriale of the National Academy Press. The term mandala comes from Sanskrit, and such motifs are prominent among many of the world's religions. In psychology, mandalas were studied and used most extensively by the psychiatrist Carl Jung, who viewed mandalas as abstract representations of the totality of the conscious and unconscious. Universal elements of the unconscious, or archetypes, were important in Jung's theory of individual psychological development and manifestations, but also were evident in symbols, myths, legends, and rituals. Color reprints of some of Jung's patient's mandalas are contained in R.F.C. Hull's English translation of Jung's book, The Archetypes and the Collective Unconscious (Second Edition, Tenth Printing; Princeton, NJ: Princeton University Press, 1990).

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COMMITTEE TO IDENTIFY STRATEGIES TO RAISE THE PROFILE OF SUBSTANCE ABUSE AND ALCOHOLISM RESEARCH NANCY C. ANDREASEN, (Chair),* Andrew H. Woods Professor of Psychiatry and Director, Mental Health Clinical Research Center, University of Iowa, Iowa City, Iowa STANLEY J. WATSON, Jr. (Vice-Chair),* Codirector and Research Scientist, Mental Health Research Institute, and Professor and Associate Chair for Research, Department of Psychiatry, School of Medicine, University of Michigan, Ann Arbor, Michigan MICHAEL BYAS-SMITH, Assistant Professor of Anesthesiology, Emory Anesthesiology Administration, Atlanta, Georgia MARC G. CARON, Investigator, Howard Hughes Medical Institute, and Professor, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina BRIAN M. COX, Professor and Chairman, Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland JOHN GRABOWSKI, Professor, Department of Psychiatry and Behavioral Science, University of Texas Health Science Center, Houston, Texas SHARON M. HALL, Professor and Vice-Chairperson, Department of Psychiatry, School of Medicine, University of California at San Francisco, San Francisco, California STEVEN E. HYMAN, Director, National Institute of Mental Health, Rockville, Maryland TING-KAI LI, Distinguished Professor of Medicine and Biochemistry, School of Medicine, Indiana University, Indianapolis, Indiana HERBERT W. NICKENS, Vice President for Community and Minority Programs, Association of American Medical Colleges, Washington, D.C. DOROTHY P. RICE,* Professor Emeritus, Institute for Health and Aging, University of California at San Francisco, San Francisco, California SALLY SATEL, Research Psychiatrist, School of Medicine, Yale University, Washington, D.C. WILLIAM K. SCHMIDT, President and CEO, NorthStar Research and Development, Ltd., Newark, Delaware RICHARD W. TSIEN,* George D. Smith Professor and Chairman, Department of Molecular and Cellular Physiology, School of Medicine, Stanford University, Stanford, California JUDITH R. WALTERS, Chief, Neurophysiological Pharmacology Section, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland *   Institute of Medicine member.

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STEPHEN M. WEISS, Professor and Codirector, Division of Behavioral Medicine and Consultation Psychiatry, School of Medicine, University of Miami, Miami, Florida Institute of Medicine Staff LAUREN B. LEVETON, Study Director until September 1996 CARRIE E. INGALLS, Research Associate THOMAS J. WETTERHAN, Project Assistant/Research Assistant AMELIA B. MATHIS, Project Assistant TERRI SCANLAN, Administrative Assistant DIANA ZUCKERMAN, Consultant MICHAEL A. STOTO, Director, Division of Health Promotion and Disease Prevention CONSTANCE M. PECHURA, Director, Division of Neuroscience and Behavioral Health

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Preface Research on addiction reveals fascinating paradoxes and contradictions. On one hand, there are enormous opportunities, such as those for furthering knowledge about the complex and sophisticated science of neurobiology. Scientists have identified many of the brain mechanisms that lead human beings to develop the cravings and physical dependencies that characterize addiction. These mechanisms appear to be at work with many different types of drugs, ranging from commonly used legal drugs, such as nicotine, to illicit drugs, such as heroin, which are abused and, in some individuals, lead to addiction. There are enormous barriers, however, based on stigma and misunderstanding, which have undermined the benefits of increased scientific knowledge. To address this problem effectively, the public, health educators, policymakers, and clinicians who treat addiction must be educated about research accomplishments and critical questions, and additional researchers must be recruited into the field. This report attempts to identify key barriers that need to be overcome before a rational, science-based approach to drug addiction, one of our most pressing public health problems, can be achieved. Many Institute of Medicine (IOM) studies are intended to serve as instruments of change that will shape future policies. The charge to the Committee on Raising the Profile of Substance Abuse and Alcoholism Research was to conduct a study and to develop a report to identify and address barriers to public understanding of the field and those that present obstacles for attracting and sustaining talented investigators and other health professionals who wish to pursue careers in addiction research. The committee was also charged with developing strategies to overcome the barriers.

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As work on this study progressed, a novel situation unfolded: the process itself became a catalyst for change. Committee members learned from one another—basic researchers from clinical and behavioral researchers, senior from younger, and those outside the field from those within. In particular, a workshop held in March of 1996 brought committee members, young* and senior investigators, and other health professionals and policymakers together in a meeting that helped to begin changes in attitudes and increases in knowledge (see Appendix A for the workshop agenda and Appendix B for a list of participants). The workshop provided new insights, encouraged constructive debate, and ultimately achieved consensus about the various barriers; it also stimulated innovative thinking about critical strategies. The results of the workshop and committee deliberations are presented in this report, which we hope will also be an instrument of change. It is addressed to several audiences, but particularly to the lay public, college and graduate students, university administrators, policymakers, and others who may be interested in understanding drug abuse and addiction. This report sets forth a strategy to dispel the myths about addiction and to facilitate a better understanding of the accomplishments in addiction research and the critical questions that remain to be answered (Chapters 3, 4 and 5). Addiction to nicotine, alcohol, and illegal drugs is a preventable and treatable brain disease influenced by complex sets of behaviors that may be the results of genetic, biological, psychosocial, and environmental interactions, as this report emphasizes. The costs of these problems are high and underscore the need to approach the problems from a perspective that is more rational and evidence based. The committee of 16 members was carefully selected to represent basic, clinical, and behavioral researchers both inside and outside the field of drug addiction with expertise spanning different disciplines (e.g., neuroscience, psychopharmacology, anesthesiology, behavioral medicine, economics) and different substances (e.g., nicotine, alcohol, opioids, stimulants). They were also selected for their experience in careers associated with academia, government, and industry. In addition, to improve understanding as to how various barriers may pose problems at different stages of a research career, the committee was selected to be representative of those different stages, ranging from junior to more senior researchers and clinicians. The committee collected quantitative and qualitative data during the study, including data on prevalence and costs of addiction (Chapter 2), efforts made in educational settings from early grades through medical schools (Chapter 6), investments in research and training (Chapter 7), and initiatives to educate the *   Young investigators were defined for the purpose of this study not by chronological age, but rather as individuals who were at early stages of their careers.

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public and the role of public perception in supporting or inhibiting increased understanding and implementation of effective public policies regarding research (Chapter 8). The day-and-a-half workshop was a major data gathering activity that helped to shape the search for information and enriched the committee discussions. The workshop highlighted young investigators' perceptions of their experiences of the barriers and opportunities in pursuing careers in addiction research and treatment. The young investigators represented the entire spectrum of career pathways, from predoctoral and premedical students to recent postdoctoral and junior faculty individuals. In addition, they represented career paths spanning neurobiological, clinical, and behavioral areas both inside and outside addiction research and treatment. The workshop also included a broad representation of other individuals—senior investigators inside and outside addiction research, and medical and health professionals and policymakers representing universities, foundations, industry, government, and professional associations interested in addiction research. Seventy people participated in the workshop and an additional 29 young investigators and 25 senior investigators and other professionals provided written contributions about their perceptions and experiences of barriers and strategies for attracting individuals into the field (Appendix B contains the list of workshop participants and contributors). The committee also heard about advances in addiction research from two keynote speakers, Drs. Avram Goldstein and Ivan Diamond, who shared valuable perspectives based on their extensive experience in this field (Appendixes C and D). Finally, to obtain a perspective on lessons learned, three speakers described how their fields had advanced and overcome the barriers posed by stigma. The fields (depression, epilepsy, and breast cancer) were selected by the committee to illustrate success stories that could serve as role models for advancing the field of addiction research. Many individuals helped the committee do its work, but first we would like to thank the W.M. Keck Foundation of Los Angeles for their financial support, without which this study would not have taken place. We would like to thank the committee members for their dedication and diligence, but most of all for their open-mindedness and flexibility. Each made a unique contribution and broadened our perspective. We also appreciate the efforts of a number of people who obtained and provided information on the various federal agencies and their funding, and shared their knowledge and perspectives through interviews and questionnaires. Several people provided valuable assistance in preparing chapter drafts, workshop summaries, and in copy editing the manuscript (Diana Zuckerman, Sara Brookhart, Peter Slavin, and Beth Gyorgy). Most particularly, we are grateful to the IOM staff: Lauren Leveton for assuming in-house leadership for the study and the organization of the workshop until September 1996; Constance Pechura for providing wise oversight; Carrie Ingalls for exceptional

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research and writing assistance; Thomas Wetterhan for additional skilled research support, manuscript preparation, and logistical support; Terri Scanlan for consistently helpful administrative assistance; and Amelia Mathis for making our travel, meeting arrangements and meals comfortable and enjoyable. Also, we appreciate the efforts of Michael Edington, managing editor, Claudia Carl, administrative associate for report review, and Carlos Gabriel, financial associate. Finally, we would like to thank all the young investigators who have much to look forward to as they pursue the exciting challenges in addiction research. NANCY C. ANDREASEN M.D., PH.D., Chair STANLEY WATSON, M.D., PH.D., Vice-Chair

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Contents     SUMMARY   1 1   INTRODUCTION   11     Definitions and Concepts   13     Classification of Drugs   14     Organization of the Report   16 2   PREVALENCE, COSTS, AND INVESTMENTS   19     Prevalence   19     Economic Costs of Addiction   25     Investments   28     Conclusion   32 3   NEUROBIOLOGY OF ADDICTION: AN OVERVIEW   37     The Brain's Common "Reward" Pathway   39     Drug Effects on Brain Reward Systems   41     Emotion, Memory, and the Transition from Use to Addiction   42     Vulnerabilities to Addiction   47     Conclusion   49 4   PSYCHOSCIAL FACTORS AND PREVENTION   55     Psychosocial Factors   55     Prevention   57     Conclusion   66

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5   TREATING ADDICTIVE DISORDERS   73     Treatments for Alcohol and Cocaine Addiction   75     Treatments for Opioid Addiction   83     Smoking Cessation Programs   85     Conclusion   87 6   EDUCATION AND TRAINING   95     Career Pathways   96     Secondary School and Undergraduate Education   97     Graduate and Professional Education   99     The Importance of Mentors   106     Specialization and Credentialing Issues   109     Conclusion   111 7   RESOURCES NEEDED FOR YOUNG INVESTIGATORS   115     Funding Levels   119     The Pipeline   120 8   PUBLIC PERCEPTIONS, PUBLIC POLICIES   139     Stigma   139     Advocacy   141     A Model for Understanding the Educational and Public Barriers   142     Strategies   142     APPENDIXES         A Workshop Agenda   149     B Workshop Contributors and Participants   153     C Plenary Lecture I, Avram Goldstein, M.D.   161     D Plenary Lecture II, Ivan Diamond, M.D., Ph.D.   169     E History of Drug Addiction Research: Key Discoveries/Events, National Policies, and Funding   177     F Recent Advances in Addiction Research   193     G Recent Advances in Pharmacotherapy   199     H Recent Advances in Behavioral Sciences and Treatment   201     I Key Barriers and Critical Strategies in the Research and Public Arenas   205     INDEX   211

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TABLES, FIGURES, AND BOXES Tables 1.1   Classification of Abusive and Addictive Drugs   17 2.1   Trends in Past Month Use of Marijuana, Alcohol, and Cigarettes by 8th Graders, 10th Graders, and High School Seniors, 1992–1996   24 2.2   Estimated Economic Costs of Illicit Drug, Alcohol, and Nicotine Abuse, 1990 (Millions of Dollars)   26 2.3   Costs of Illness for Selected Diseases and Conditions (Billions of Dollars)   29 2.4   NIDA Funding History (1988–1997): Research Training Grants, Research Grants, and Total Budget (Thousands of Dollars)   31 2.5   NIAAA Funding History (1988–1997): Research Training Grants, Research Grants, and Total Budget (Thousands of Dollars)   31 3.1   Some Future Challenges in Basic Research   50 4.1   Some Future Challenges in Psychosocial and Prevention Research   67 5.1   Duration of Addiction Treatment   76 5.2   Some Future Challenges in Pharmacotherapy and Treatment Research   88 7.1   Total Costs to Society and Training and Research Support for Specific Diseases (Millions of Dollars)   119 7.2   R01 Success Rates   129 7.3   NIDA Research Training Funding as a Percentage of Total Extramural Research Funding (Millions of Dollars)   130 7.4   NIAAA Research Training Funding as a Percentage of Total Extramural Research Funding (Millions of Dollars)   130 Figures 2.1   Past Month Illicit Drug Use by Age: 1979–1995   20 2.2   Past Month Illicit Drug Use, by Past Month Alcohol Use, Age 12 and Older, 1995   22 2.3   Economic Costs of Addiction by Type of Cost and Drug, 1990   27 3.1   Schematic Diagram of the Brain Reward Circuitry   40 3.2   The Effect of Cocaine and Amphetamine   42 7.1   Total Institute Budgets, 1986–1995 (Constant Dollars)   122 7.2   Total Institute Research Grant Budgets, 1986–1995 (Constant Dollars)   123 7.3   Total Research Training Grant Budgets, 1986–1995 (Constant Dollars)   124 7.4   Total Number of T32, F31, and F32 Applicants, 1986–1995   125 7.5   Total Number of T32, F31, and F32 Awards Granted, 1986–1995   126 7.6   Total Number of R01 and R29 Applicants, 1986–1995   127 7.7   Total Number of R01 and R29 Awards Granted, 1986–1995   128

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8.1   Critical Links in the Strategies for Raising the Profile of Addiction Research   143 Boxes 2.1   Estimating the Cost of Drug Abuse in New York City   28 3.1   Animal Models: Examples from Alcohol Research   38 3.2   Effects of Alcohol on Neurotransmission   43 6.1   American Association for the Advancement of Science   98 6.2   Faculty for Undergraduate Neuroscience   99 6.3   Case Study: Harvard Medical School, Division on Addictions   102 6.4   Case Study: University of Pennsylvania, School of Medicine   103 6.5   North Carolina Governor's Institute on Alcohol and Substance Abuse, Inc.   105 7.1   Description of Awards   116 7.2   Foundation-Funded Research: A Model Program   132

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Acronyms AA Alcoholics Anonymous AAAS American Association for the Advancement of Science AAMC Association of American Medical Colleges ABPN American Board of Psychiatry and Neurology ACS American Cancer Society ADA American Diabetes Association ADD attention-deficit disorder ADH alcohol dehydrogenase ADHD attention-deficit hyperactivity disorder AHA American Heart Association AHCPR Agency for Health Care Policy and Research, United States Department of Health and Human Services AHEC Area Health Education Centers AIDS acquired immunodeficiency syndrome ALDH2 aldehyde dehydrogenase AMA American Medical Association AMERSA Association for Medical Education and Research in Substance Abuse APA American Psychological Association ASA American Sociological Association ASAM American Society of Addiction Medicine ATP adenosine triphosphate AVP arginine vasopressin B/START Behavioral Science Track Award for Rapid Transition

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BAC blood alcohol concentrations BLS Bureau of Labor Statistics cAMP cyclic adenosine monophosphate CASA Center on Addiction and Substance Abuse CCK-8 cholecystokinin-8 cDNA deoxyribonucleic acid, complementary sequence cm centimeters CME continuing medical education CNS central nervous system CRA community reinforcement approach CRF corticotropin releasing factor CSAP Center for Substance Abuse Prevention CSAT Center for Substance Abuse Treatment DARP Drug Abuse Reporting Project DEA Drug Enforcement Administration delta-9-THC delta-9-tetrahydrocannabinol DHHS Department of Health and Human Services DMT dimethyltryptamine DNA deoxyribonucleic acid DoD Department of Defense DOM dimethoxymethylamphetamine DOT Department of Transportation DSM-III-R Diagnostic and Statistical Manual of Mental Disorders—Third Edition Revised DSM-IV Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition DWI driving while intoxicated F30 Individual Predoctoral National Research Service Award for M.D./Ph.D. Fellowships F31 Individual Predoctoral National Research Service Award for Fellows F32 Individual Postdoctoral National Research Service Award for Fellows FAS fetal alcohol syndrome FDA Food and Drug Administration FHN familial high-alcohol nonpreferring FHP familial high-alcohol preferring FUN Faculty for Undergraduate Neuroscience GABA gamma-aminobutyric acid GAO General Accounting Office HCFA Health Care Financing Administration HCl hydrochloride

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HDL high-density lipoprotein HIV human immunodeficiency virus HRSA Health Research and Services Administration ICD International Classification of Disease IOM Institute of Medicine IRB institutional review board IRG initial review group K01 Mentored Research Scientist Development Award K02 Independent Scientist Award K05 Senior Scientist Award K07 Academic Career Award K08 Mentored Clinical Scientist Development Award kcal kilocalories LAAM levo-alpha-acetylmethadol or levomethadyl acetate, trade name: Orlaam® LCME Liaison Committee on Medical Education LRP Loan Repayment Program LSD lysergic acid diethylamide LTA latent transition analysis MATCH Matching Alcohol Treatment to Client Heterogeneity MDA methylenedioxyamphetamine MDD Medications Development Division MDMA methylenedioxymethamphetamine mg milligram mm millimeter MMWR Morbidity and Mortality Weekly Report MOU memorandum of understanding MSTP Medical Sciences Training Program NAc nucleus accumbens NAMA National Alliance of Methadone Advocates NAMI National Alliance for the Mentally Ill NARSAD National Alliance for Research on Schizophrenia and Depression NAS National Academy of Sciences NBCC National Breast Cancer Coalition NCHGR National Center for Human Genome Research NCHS National Center for Health Statistics NCI National Cancer Institute NCRR National Center for Research Resources NEI National Eye Institute NHLBI National Heart, Lung, and Blood Institute NIA National Institute on Aging

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NIAAA National Institute on Alcohol Abuse and Alcoholism NIAID National Institute of Allergy and Infectious Diseases NIAMS National Institute of Arthritis and Musculoskeletal and Skin Diseases NICHD National Institute of Child Health and Human Development NIDA National Institute on Drug Abuse NIDCD National Institute on Deafness and Other Communication Disorders NIDDK National Institute of Diabetes and Digestive and Kidney Diseases NIDR National Institute of Dental Research NIEHS National Institute of Environmental Health Sciences NIGMS National Institute of General Medical Sciences NIH National Institutes of Health NIMH National Institute of Mental Health NINDS National Institute of Neurological Disorders and Stroke NINR National Institute of Nursing Research NMDA N-methyl-D-aspartate NRC National Research Council NRSA National Research Service Awards OER Office of Extramural Research ONDCP Office of National Drug Control Policy OTA Office of Technology Assessment OTC over-the-counter PCP phencyclidine PET positron-emission tomography PTSD posttraumatic stress disorder QTL quantitative trait loci R01 Investigator Initiated Research Project R03 Small Grant R21 Exploratory/Developmental Grant R29 FIRST Award—First Independent Research Support and Transition Award R37 MERIT Award—Method to Extend Research in Time Award RFA request for applications RFP request for proposals RI recombinant inbred RWJF Robert Wood Johnson Foundation SAMHSA Substance Abuse and Mental Health Services Administration SOAR The Society of American Recovery SPECT single photon emission computed tomography

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T32 National Research Service Award Institutional Research Training Grant T35 National Research Service Award Short-Term Institutional Research Training Grant THC tetrahydrocannabinol TOPS Treatment Outcomes Prospective Study VTA ventral tegmental area WHO World Health Organization

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