Tobacco Documents Online

John P. Pierce, M.Sc., Ph.D, Chief, Edidemiology Branch, Office on Smoking and Health, Center for Health Promotion and Education, Centers for Disease Control, Rockville, Maryland Ovide F. Pomerleau, Ph.D., Behavioral Medicine Program, Universi- ty of Michigan, Department of Psychiatry, Ann Arbor, Michigan Amelie G. Ramirez, M.P.H., Faculty Associate, The University of Texas Health Science Center, Assistant Professor, Baylor College of Medicine, Houston, Texas Jed E. Rose, Ph.D., Veterans' Administration Medical Center, Wadsworth and Brentwood Divisions, Los Angeles, California J.A. Rosecrans, Ph.D., Department of Pharmacology, Medical Col- lege of Virginia, Virginia Commonwealth University, Richmond, Virginia Mary Anne Salmon, Ph.D., Research Associate, Health Services Research Center~ University of North Carolina, Chapel Hill, North Carolina Nina G. Schneider, Ph.D., Associate Research Psychologist, Depart- ment of Psychiatry and Biobehaviorai Sciences, UCLA School of Medicine, Research Psychologist, Psychopharmacology Unit, Vet- erans' Administration Medical Center, Brentwood Division, Los Angeles, California V.J. Schoenbach, Ph.D., Associate Professor, Department of Epide- miology, Research Associate, Health Services Research Center, University of North Carolina, Chapel Hill, North Carolina Saul Shiffman, Ph.D., Associate Professor, Department of Psycholo- gy, University of Pittsburgh, Pittsburgh, Pennsylvania Victor J. Strecher, Ph.D., Research Associate, Health Services Research Center, Assistant Professor, Department of Health Education, University of North Carolina, Chapel Hill, North Carolina David M. Warburton, Professor, Department of Psychology, Univer- sity of Reading, Whiteknighte, Reading, United Kingdom Elizabeth A. Wells, Ph.D., Past-Docteral Fellow, Center for Social Welfare Research, University of Washington, Seattle, Washington Thomas Ashby Wills, Ph.D., Assistant Professor of Psychology, Assistant Professor of Epidemiology and Social Medicine, Depart- ment of Epidemiology and Social Medicine, Ferkauf Graduate School of Psychology and Albert Einstein College of Medicine, Bronx, New York Phillip P. Woodson, Dr.sc.nat., Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland The editors acknowledge with gratitude the following distin- guished scientists, physicians, and others who lent their support in the development of this Report by coordinating manuscript prepara- tion, contributing critical reviews of the manuscript, or assisting in other ways. xii •

Leo G. Abood, Ph.D., Department of Pharmacology, University of Rochester Medical Center, Rochester, New York John S. Baer, Ph.D., Department of Psychology, University of Washington, Seattle, Washington Timothy B. Baker, Ph.D., Department of Psychology, University of Wisconsin, Madison, Wisconsin Claudia R. Baquet, M.D., M.P.H., Chief, Special Populations Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland Glen Bennett, M.P.H., Field Studies Advisor, Office of Prevention, Education, and Control, National Heart, Lung, and Blood Insti- tute, Bethesda, Maryland George E. Bigelow, Ph.D., Associate Professor of Behavioral Biology, Director, Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins Universi- ty School of Medicine, Baltimore, Maryland Clarice Brown, M.S., Data Analyst, Office of Prevention, Education, and Control, National Heart, Lung, and Blood Institute, Bethesda, Maryland David M. Burns, M.D., Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Medical Center, San Diego, California Donald R. Cherek, Ph.D., Department of Psychiatry and Behavioral Sciences, Mental Sciences Institute, The University of Texas Health Science Center, Houston, Texas Paul B.S. Clarke, Ph.D., Department of Pharmacology and Thera- peutics, McGin University, Montreal, Quebec, Canada Re Nemeth-Coslett, Ph.D., Psychologist, Prevention Research Branch, Division of Clinical Research, National Institute on Drug Abuse, Rockville, Maryland Thomas J. Crowley, M.D., University of Colorado Health Sciences Center, Denver, Colorado Joseph W. Cullen, Ph.D., Deputy Director, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland K. Michael Cummings, Ph.D., M.P.H., Research Scientist, Depart- ment of Cancer Control and Epidemiology, Roswell Park Memorial Institute, Buffalo, New York Susan Curry, Ph.D., Center for .Health Studies, Group Health Cooperative of Puget Sound, Seattle, Washington Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Sir Richard Doll, University of Oxford, Oxford, England Manning Feinleib, M.D., Dr.P.H., Director, National Center for Health Statistics, Centers for Disease Control, Hyattsville, Mary- land xiii

Richard R. Frecker, M.D., Ph.D., Head, Biomedical Research, Department of Pharmacology, Addiction Research Foundation, Toronto, Ontario, Canada K.H. Ginzel, Ph.D., Professor, Department of Pharmacology and Interdisciplinary Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas Russell E. Glasgow~ Ph.D., Oregon Research Institute, Eugene, Oregon Nancy P. Gordon, Sc.D., Behavioral Scientist, Division of Research, Kaiser Permanente Medical Group, Oakland, California Roland R. Grlffiths, The Johns Hopkins University School of Medicine, Baltimore, Maryland Ellen R. Gritz, Ph.D., Director, Division of Cancer Control, Joasson Comprehensive Cancer Center, University of California, Los Angeles, California Sharon M. Hall, Ph.D., Professor, Department of Psychiatry, Center for Social and Behavioral Sciences, University of California, San Francisco, California Louis S. Harris, Ph.D., Senior Science Advisor, National Institute on Drug Abuse, Alcohol, Drug Abuse, and Mental Health Administra- tion, Rockville, Maryland Ronald I. Herning, Ph.D., Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland Dietrich Hoffmann, Ph.D., Associate Director, Naylor Dana Insti- tute, Valhalla, New York Leo Hollister, M.D., Medical Director, Harris County Psychiatry Center, Houston, Texas Enid Hunkeler, Senior Investigator, Kaiser Permanente Medical Care Program, Oakland, California Peyton Jacob III, Ph.D., Division of Clinical Pharmacology, San Francisco General Hospital, University of California, San Francis- co, California Jerome Jaffas, M.D., Director, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MaiTland Murray E. Jarvik, M.D., Ph.D., The Neuropsychatric Institute and Hospital School of Medicine, University of California, Los Angeles, and Veterans' Administration Medical Center West Los Angeles, Brentwood Division, Los Angeles, California Martin Jarvis, M.Phil., Senior Lecturer, Addiction Research Unit, Institute of Psychiatry, London, England Chris-Ellen Johanson, Ph.D., Department of Psychiatry, Pritzker School of Medicine, University of Chicago Drug Abuse Research Center, Chicago, Illinois Reese T. Jones, Ph.D., Department of Psychiatry, University of California School of Medicine, San Francisco, California xiv •

Ken J. Kellar, Ph.D., Department of Pharmacology, Georgetown University Medical Center, Washington, D.C. Lynn T. Kozlowski, Ph.D., Head, Behavioral Research on Tobacco Use, Addiction Research Foundation, Toronto, Ontario, Canada Richard J. Lamb, Ph.D., Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland Charles L. LeMaistre, M.D., President, University of Texas Systems Cancer Center, Houston, Texas Claude Lenfant, M.D., Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Howard Leventhal, Ph.D., Professor of Psychology, University of Wisconsin, Madison, Wisconsin Edward Lichtenstein, Ph.D., Oregon Research Institute, Eugene, •Oregon Donald Inn Macdonald, M.D., Administrator, Alcohol, Drug Abuse, and Mental Health Administration, RockviUe, Maryland G. Alan Marlatt, Ph.D., Professor of Psychology, University of Washington, Seattle, Washington William R. Martin, M.D., Chairman, Department of Pharmacology, University of Kentucky College of Medicine, Lexington, Kentucky James O, Mason, M.D., Dr.P.H., Director, Centers for Disease Control, Atlanta, Georgia J. Michael McGinnis, M.D., Deputy Assistant Secretary (Disease Prevention and Health Promotion), Washington, D.C, A. Thomas MeLelian, Ph.D., Substance Abuse Treatment Research Center, Philadelphia Veterans' Administration Medical Center and The University of Pennsylvania, Philadelphia, Pennsylvania Nancy K. Mello, Ph.D, Alcohol and Drug Abuse Research Center, McClean Hospital, Belmont, Massachusetts Gregory J. Morasco, Ph.D., M.P.H., Smoking Education Program Coordinator, National Heart, Lung, and Blood Institute, Bethesda, Maryland Joseph P. Mulholland, Ph.D., Bureau of Economics, Federal Trade Commission, Washington, D.C. Herbert W. Niekens, M.D., M.A., Director, Office of Minority Health, Public Health Service, Washington, D.C. Richard Pete, M.A., M.Sc., Imperial Cancer Research Fund, Cancer Studies Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, University of Oxford, Oxford, England Roy W. Pickens, Ph.D., Director, Division of Clinical Research, National Institute on Drug Abuse, Rockville, Maryland John P. Pierce, M.Sc., Ph.D., Chief, Epidemiology Branch, Office on Smoking and Health, Center for Health Promotion and Education, Centers for Disease Control, Rockville, Maryland XV

John M. Pinney, Executive Director, Institute for the Study of Smoking Behavior and Policy, John F. Kennedy School of Govern- ment, Harvard University, Cambridge, Massachusetts Michael R. Polen, M.A., Research Associate, Division of Research, Kaiser-Permanento Medical Group, Oakland, California William Pollin, M.D., Former Director, National Institute on Drug Abuse, Bethesda, Maryland David C. Ramsey, M.P.H., Health Educator, Division of Health Education, Center for Health Promotion and Education, Centers for Disease Control, Atlanta, Georgia Everett R. Rhoades, M.D., Assistant Surgeon General and Director, Indian Health Service, Rockville, Maryland M.A.H. Russell, F.R.C.P., Addiction Research Unit, Institute of Psychiatry, University ofLondon, London, England Charles R. Schuster, Ph.D., Director, National Institute on Drug Abuse, Rockville, Maryland Burt Sharpe, M.D., Hennepin County Medical Center, Department of Medicine, Minneapolis, Minnesota Donald R. Shopland, Public Health Advisor, Smoking, Tobacco, and Cancer Program, National Cancer Institute, Bethesda, Maryland Jerome E. Singer, Ph.D., Medical Psychology, Uniformed Services University of the Health Sciences, Bethesda, Maryland Maxine L. Stitzer, Ph.D, Associate Professor, Behavioral Biology, The Johns Hopkins School of Medicine; Behavioral Pharmacology Research, Francis Scott Key Medical Center, Baltimore, Maryland David N. Sundwall, M.D., Assistant Surgeon General and Adminis- trator, Health Resources and Services Administration, Rockville, Maryland Dennis D. Tolsma, M.P.H., Director, Center for Health Promotion and Education, Centers for Disease Control, Atlanta, Georgia Frederick L. Trowbridge, M.D., Director, Division of Nutrition, Center for Health Promotion and Education, Centers for Disease Control, Atlanta, Georgia Frank J. Voccl, Jr., Ph.D., Acting Chief, Drug Abuse Staff, Center for Drug Evaluation and Research, Food and Drug Administration, Washington, DC Ronald W. Wilson, M.A., National Center for Health Statistics, Centers for Disease Control, Hyattsville, Maryland Roy A. Wise, Ph.D., Department of Psychology, Concordia Universi- ty, Montreal, Quebec, Canada Faye Wright, Center for Applied Psychological Research, Depart- ment of Psychology, Memphis State University, Memphis, Tennes- see Ernst L. Wynder, M.D., President, American Health Foundation, New York, New York ×vi

James B. Wyngaarden, M.D., Director, National Institutes of Health, Bethesda, Maryland Tomoji Yanagita, M.D., Ph.D., Preclinical Research Laboratories, Central Institute for Experimental Animals, Kawasaki, Japan Frank E. Young, M.D., Commissioner, Food and Drug Administra- tion, Rockville, Maryland The editors also acknowledge the contributions of the following staff members and others who assisted in the preparation of this Report. Margaret Anglia, Secretary, Office on Smoking and Health, Rock- vine, Maryland Charles Appiah, Project Clerk, Smoking and Health Project, The Circle, Inc., McLean, Virginia John L. Bagroski, Associate Director for Program Operations, Office on Smoking and Health, Rockville, Maryland Sonia Balakirsky, Secretary, Office on Smoking and Health, Rock- ville, Maryland Carol Bean, Associate Project Director, Smoking and Health Project, The Circle, Inc., McLean, Virginia Tamara Blair, Production Coordinator, Information Management Department, ATLIS Federal Services, Inc., Rockville, Maryland Catherine E. Burckhardt, Editorial Assistant, Office on Smoking and Health, Rockville, Maryland Gayle Christman, Word Processing Specialist, Smoking and Health Project, The Circle, Inc., McLean, Virginia Carol K. Cummings, Secretary, Office on Smoking and Health, Roekville, Maryland Stephanie D. DeVoe, Programmer, Information Systems Depart-ment, ATLIS Federal Services, Inc., Rockville, Maryland Michael C. Fiore, M.D., M.P.H., Medical Epidamiologist, Office on Smoking and Health, Rockville, Maryland David Fry, Editor, Smoking and Health Project, The Circle, Inc., McLean, Virginia Lynn Funkhauser, Word Processing Specialist, Smoking and Health Project, The Circle, Inc., McLean, Virginia Mary Gardner, Senior Editor, Smoking and Health Project, The Circle, Inc., McLean, Virginia Amy Garson, M.P.H. student, Office on Smoking and Health, Rockville, Maryland Arnetta G. Glover, Secretary, Office on Smoking and Health, Rockville, Maryland Evridiki Hatziandreu, M.D., M.P.H., Epidemic Intelligence Service Officer, Office on Smoking and Health, Rockville, Maryland Patricia E. Healy, Technical Information Specialist, Office on Smoking and Health, Rockville, Maryland xvii

Terri L. Henry, Clerk-Typist, Office on Smoking and Health, Rockvine, Maryland Timothy K. Hensley, Technical Publications Writer, Office on Smoking and Health, Rockville, Maryland Shirley K. Hickman, Data Entry Operator, Information Manage- ment Department, ATLIS Federal Services, Inc., Rockville, Mary- land Robert S. Hutchings, Associate Director for Information and Pro- gram Development, Office on Smoking and Health, Rockville, Maryland Karen Jacob, Senior Editor, Smoking and Health Project, The Circle, Inc., McLean, Virginia Sheila Jones, Word Processing Specialist, Smoking and Health Project, The Circle, Inc., McLean, Virginia R~ck Keir, Senior Editor, Smoking and Health Project, The Circle, Inc., McLean, Virginia Julie Kurz, Graphics Specialist, Information Management Depart- ment, ATLIS Federal Services, Inc., Rockville, Maryland Gerri E. Mast, Secretary, Center for Health Promotion and Educa- tion, Centers for Disease Control, Atlanta, Georgia Judy J. Mast, Secretary, Center for Health Promotion and Educa- tion, Centers for Disease Control, Atlanta, Georgia Dixie McGough, Program Manager, Information Management De- partment, ATLIS Federal Services, Inc., Rockville, Maryland Dan McLaughlin, Editorial Assistant, Smoking and Health Project, The Circle, Inc., McLean, Virginia Nancy Miltenberger, Editor, Smoking and Health Project, The Circle, Inc., McLean, Virginia Cathie O'Donnell, Senior Editor, Smoking and Health Project, The Circle, Inc., McLean, Virginia Ruth C. Palmer, Secretary, Office on Smoking and Health, Rockville, Maryland Russell D. Peek, Library Acquisitions Specialist, Information Man- agement Department, ATLIS Federal Services, Inc., Rockville, Maryland Margaret E. Pickerel, Public Information and Publications Special- ist, Office on Smoking and Health, Rockville, Maryland Renate Phillips, Desktop Publishing/Graphic Artist, Smoking and Health Project, The Circle, Inc., McLean, Virginia Karen Sherman, Production Assistant, Information Management Department, ATLIS Federal Services, Inc., Roekville, Maryland Linda R. Spiegelman, Administrative Officer, Office on Smoking and Health, Roekville, Maryland Tamara Shipp, Publications Assistant, Smoking and Health Project, The Circle, Inc., McLean, Virginia xviii •

O Evelyn L, Swarr, Systems Management Projects Supervisor, Infor- mation Systems Department, ATLIS Federal Services, Ino,, Rock. ville, Maryland Daniel R. Tisch, Project Director, Smoking and Health Project, The Circle, Inc., McLean. Virginia Louise G. Wiseman, Technical Information Specialist~ Office on Smoking and Health, Rockville, Maryland O xix

TABLE OF CONTENTS Foreword ................................................................. i Preface .................................................................. ill Acknowledgments .......... : ......................................... ix I. Introduction, Overview, Summary, and ' Conclusions ..................................................... 1 II. Nicotine: Pharmacokinetics, Metabolism, and Phar- maeodynamies ................................................. 21 III. Nicotine: Sites and Mechanisms of Actions ........... 75 IV. Tobacco Use and Drug Dependence ................... 145 V. Tobacco Use Compared to Other Drug Dependencies ............................................. :... 241 VI. Effects of Nicotine That May Promote Tobacco Use ......................................................... :.,.. 375 VII. Treatment of Tobacco Dependence ..................... 459 Appendix A: Trends in Tobacco Use in the United States ............................................... 561 Appendix B: Toxicity of Nicotine ............................. 589 xxi

CHAPTER I INTRODUCTION, OVERVIEW, SUMMARY, AND CONCLUSIONS