ADDICTIONS

A COMPREHENSIVE GUIDEBOOK
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 ADDICTIONS
A COMPREHENSIVE GUIDEBOOK

EDITED BY

Barbara S. McCrady
Elizabeth E. Epstein

New York Oxford

Oxford University Press
1999
 Oxford University Press
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Copyright © 1999 by Oxford University Press, Inc.

Published by Oxford University Press, Inc.
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Oxford is a registered trademark of Oxford University Press
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means,
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without the prior permission of Oxford University Press.

Library of Congress Cataloging-in-Publication Data

McCrady, Barbara S.
Addictions : a comprehensive guidebook / Barbara S. McCrady,
Elizabeth E. Epstein.
p. cm.
Includes index.
ISBN 0-19-511489-2
1. Substance abuse. 2. Alcoholism. 3. Drug abuse. I. Epstein,
Elizabeth E. II. Title.
RC564.M327 1999
616.86-dc21 98-51552

1 3 5 7 9 8 6 4 2
Printed in the United States of America
on acid-free paper
To Margaret Miller Sachs (1921-1994), my mother, my role model, my inspiration.—BSM

To my family—Joe, Jeremy, Eve, and Sam.—EEE

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 Foreword

Some years ago, before coming to the National Insti- titioners, unlike their predecessors, have access to an
tute on Alcohol Abuse and Alcoholism, I directed a impressive array of clinical resources to help them to
large alcoholism treatment program in New York understand, diagnose, and treat the problems of alco-
City. At that time, our major goal was a relatively hol and drug misuse. This textbook, Addictions: A
simple one: to get our patients sober and to help Comprehensive Guidebook, is a fine example of such
them remain so. The tools that we had available to a resource. It presents a wide range of subjects writ-
help accomplish this goal also were relatively sim- ten by experts from the many varied fields that im-
ple: the experience of those who had recovered pri- pact in one way or another on the treatment of alco-
marily through Alcoholics Anonymous (AA) and our hol and other drug abuse. Its breadth and scope, in
basic clinical "common sense" (i.e., approaches that fact, are a testament to how far we have come in
seemed plausible and made intuitive sense but had defining what we do and how we can do it effectively
not been validated with contemporary techniques of based not just on common sense, but on a growing
treatment outcome evaluation). The type of science- body of quality basic and behavioral research.
based information available to other health care This change from reliance solely on common
practitioners through textbooks, health professions sense to common sense and science, above all others,
training, and other sources of information sharing has led our fields to acceptance and respect by the
that we take for granted today was, with a few notable professional health care field at large. It has also led
exceptions, nonexistent just 15 years ago. to greater understanding by the public of alcohol and
Today, the simple goal of treatment that we share substance use disorders as bona fide medical condi-
as alcohol and other drug abuse scientists and prac- tions that can respond to treatment. This change is
titioners has not changed. However, today's prac- reflected in many different ways. For example, it is
viii FOREWORD

reflected in the growing recognition of the need for access to resources such as this book is a must. Here,
science-based information by policymakers and prac- in one source, is the information needed by alcohol
titioners, a need deriving in part from demands by and drug abuse specialists, primary-care providers,
managed-care organizations, other third-party insur- policymakers, and others who are involved in pro-
ers, and state and federal policymakers for the same grams which are geared to helping those who abuse
type of safety and efficacy evidence that is required or are dependent on alcohol and other drugs to be-
for all other illnesses. It is also reflected in the in- come informed about these problems, including the
creasing number of physicians' and other primary far-reaching effects of these substances on individuals
health care organizations that provide research-based and on society. I commend both Dr. McCrady and
findings about alcohol and other drug problems to Dr. Epstein for their efforts in presenting such a
their memberships. This change is also reflected in wealth of material in a clear and concise manner ap-
the extensive research effort underpinning new di- propriate for a variety of audiences, and for having
agnostic classification systems, both nationally and pulled together the talented group of subject-matter
internationally, and in the increasing attention to li- experts represented in this book.
censure and certification by professional organiza-
tions and by the states. Enoch Gordis, M.D.
Because of these and other changes in how we do Director
business, and the growing amount and complexity of National Institute on
information about alcohol and other drugs, having Alcohol Abuse and Alcoholism
 Acknowledgments

Several individuals were key to the completion of scholarship, being surrounded by colleagues con-
this book. First, we thank Larry Beutler, who recom- ducting research and clinical work related to sub-
mended both the topic and the editors to Oxford stance use and abuse, and the ready availability of
University Press. Second, we express our tremendous the outstanding alcohol studies library—all provided
appreciation to Joan Bossert at Oxford University the environment and resources necessary to com-
Press, who was patient and encouraging in our work plete this venture. Finally, our greatest appreciation
to conceptualize the book and bring it to fruition. goes to the authors and coauthors, a superb and re-
The third key individual is Karen Rhines, both a nowned group of clinicians and researchers who pro-
promising clinical psychology graduate student at duced wonderful chapters, and suffered patiently
Rutgers and an utterly organized human being who through our thorough and sometimes obsessive edit-
has served as our editorial assistant. Fourth, the work ing, to create this valuable resource for the field.
could not have been completed in a more congenial
and supportive setting than the Center of Alcohol April 1998 B.S.M.
Studies at Rutgers University. The enthusiasm for Piscataway, NJ E.E.E.
This page intentionally left blank
 Contents

Contributors xv 3. Theories of Etiology of Alcohol and Other

Drug Use Disorders 50
Introduction 3 MICHIE N. HESSELBROCK
BARBARA S. MCCRADY VICTOR M. HESSELBROCK
ELIZABETH E. EPSTEIN ELIZABETH E. EPSTEIN

I. Epidemiology, Etiology, and Course of II. Specific Drugs of Abuse: Pharmacological

Substance Use Disorders and Clinical Aspects

1. Alcohol and Drug Use, Abuse, and 4. Alcohol 75

Dependence: Classification, Prevalence, DARLENE H. MOAK
and Comorbidity 9 RAYMOND F. ANTON
BRIDGET F. GRANT
DEBORAH A. DAWSON 5. Sedative-Hypnotic and Anxiolytic Agents 95
KATHLEEN T. BRADY
2. The Course of Treated and Untreated HUGH MYRICK
Substance Use Disorders: Remission and ROBERT MALCOLM
Resolution, Relapse and Mortality 30
JOHN W. FINNEY 6. Stimulants: Amphetamines and Cocaine 105
RUDOLF H. MOOS MICHAEL F. WEAVER
CHRISTINE TIMKO SIDNEY H. SCHNOLL
xii CONTENTS

7. Cannabis and Hallucinogens 121 18. Self-Help Groups for Addictions 328
ROBERT S. STEPHENS JOSEPH NOWINSKI

8. Opioids 141 19. Pharmacotherapies 347

SUSAN M. STINE WAYNE S. BARBER
THOMAS R. KOSTEN CHARLES P. O'BRIEN

9. Nicotine 162 20. Relapse Prevention: Maintenance of Change

JOHN SLADE
After Initial Treatment 370
LORI A. QUIGLEY
10. Other Drugs of Abuse: Inhalants, Designer
G. ALAN MARLATT
Drugs, and Steroids 171
ROBERT PANDINA
21. Treatment of Drug and Alcohol Abuse:
ROBERT HENDREN
An Overview of Major Strategies and
Effectiveness 385
III. Case Identification, Assessment, and JOHN P. ALLEN
Treatment Planning RAYE Z. LITTEN

11. Assessment Strategies and Measures in

Addictive Behaviors 187 V. Practice Issues
DENNIS M. DONOVAN
22. Legal and Ethical Issues 399
12. Treatment Decision Making and FREDERICK B. GLASER
Goal Setting 216 DAVID G. WARREN
RONALD M. KADDEN
PAMELA M. SKERKER 23. Credentialing, Documentation, and
Evaluation 414
THERESA B. MOYERS
IV. Treatment
REID K. HESTER

13. Enhancing Motivation for Treatment and

Change 235 24. Interfaces between Substance Abuse Treatment
CAROLINA E. YAHNE
and Other Health and Social Systems 421
SUSAN J. ROSE
WILLIAM R. MILLER
ALLEN ZWEBEN
14. Behavioral and Cognitive Behavioral VIRGINIA STOFFEL
Treatments 250
KATHLEEN M. CARROLL
VI. Issues in Specific Populations
15. The Disease Model 268
TIMOTHY SHEEHAN
25. Treatment of Persons with Dual Diagnoses of
PATRICIA OWEN
Substance Use Disorder and Other
Psychological Problems 439
16. Treatment Models and Methods: Family
RICHARD N. ROSENTHAL
Models 287
LAURENCE WESTREICH
TIMOTHY J. O'FARRELL
WILLIAM FALS-STEWART
26. Age-Limited Populations: Youth, Adolescents,
17. The Therapeutic Community Treatment and Older Adults 477
Model 306 PILAR M. SANJUAN
GEORGE DE LEON JAMES W. LANGENBUCHER
 CONTENTS xiii

27. Ethnic and Cultural Minority Groups 499 VII. Prevention, Policy, and Economics of
FELIPE G. CASTRO Substance Use Disorders
RAE JEAN PROESCHOLDBELL
LYNN ABEITA 30. Prevention Aimed at Individuals: An Integrative
DOMINGO RODRIGUEZ Transactional Perspective 555
MARY ANN PENTZ

28. Women 527 31. Prevention Aimed at the Environment 573

EDITH S. LISANSKY GOMBERG
HAROLD D. HOLDER

29. Gay Men, Lesbians, and Bisexuals 524 32. Economic Issues and Substance Use 595
RODGER L. BEATTY JEFFREY MERRILL
MICHELLE O. GECKLE
JAMES HUGGINS Index 611
CAROLYN KAPNER
KAREN LEWIS
DOROTHY J. SANDSTROM
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 Contributors

Lynn Abeita, B.A., Graduate Research Assistant, De- Kathleen M. Carroll, Ph.D., Associate Professor,
partment of Psychology, Arizona State University, Department of Psychiatry School of Medicine, Yale
Tempe, AZ University School of Medicine, New Haven, CT
John P. Allen, Ph.D., Chief, Treatment Research Felipe G. Castro, M.S.W., Ph.D., Professor, De-
Branch, National Institute on Alcohol Abuse and Al- partment of Psychology, Arizona State University,
coholism, Bethesda, MD Tempe, AZ
Raymond F. Anton, M.D., Professor of Psychiatry,
Medical University of South Carolina, Institute of Deborah A. Dawson, Ph.D., Mathematical Statisti-
Psychiatry, Charleston, SC cian, Biometry Branch, Division of Biometry and
Epidemiology—National Institute on Alcohol Abuse
Wayne S. Barber, M.D., Director of Behavioral and Alcoholism, Bethesda, MD
Health Services, Rehoboth McKinley Christian Health
Care Services and Chairman of Psychiatry, Rehoboth George De Leon, Ph.D., Director, Center for Ther-
McKinley Christian Hospital, Gallup, NM apeutic Community Research at National Develop-
Rodger L. Beatty, Ph.D., Project Coordinator, Com- ment and Research Institutes, Inc., Research Profes-
munity AIDS Risk Reduction Project, Western Psy- sor of Psychiatry, New York University School of
chiatric Institute and Clinic, Pittsburgh, PA Medicine, New York, NY

Kathleen T. Brady, M.D., Ph.D., Associate Profes- Dennis M. Donovan, Ph.D., Director, Alcohol and
sor of Psychiatry, Department of Psychiatry and Be- Drug Abuse Institute, Professor, Department of Psy-
havioral Sciences, Medical University of South Caro- chiatry and Behavioral Sciences, University of Wash-
lina, Institute of Psychiatry, Charleston, SC ington, Seattle, WA
xvi CONTRIBUTORS

Elizabeth E. Epstein, Ph.D., Assistant Research Thomas R. Kosten, M.D., Professor of Psychiatry,
Professor, Center of Alcohol Studies, Rutgers, The Yale University School of Medicine, VA Connecti-
State University of New Jersey, Piscataway, NJ cut Healthcare System (Chief of Psychiatry Service),
West Haven, CT
William Fals-Stewart, Ph.D., Assistant Professor of
Psychology, Department of Psychology, Old Domin- James W. Langenbucher, Ph.D., Associate Profes-
ion University, Norfolk, VA sor, Research Diagnostic Project, Center of Alcohol
Studies, Rutgers, The State University of New Jersey,
John W. Finney, Ph.D., Health Science Specialist,
Piscataway, NJ
VA Palo Alto Health Care System, Center for Health
Care Evaluation, Palo Alto, CA Karen Lewis, M.A., M.H.A., C.A.C., N.C.A.C., Psy-
chologist, Private Practice, Pittsburgh, PA
Michelle O. Geckle, M.Ed., C.R.C., Senior Re-
search Associate, Western Psychiatric Institute and Raye Z. Litten, Ph.D., Program Officer, Treatment
Clinic, Pittsburgh, PA Research Branch, National Institute on Alcohol
Abuse and Alcoholism, Bethesda, MD
Frederick B. Glaser, M.D., F.R.C.P. (C), Professor
and Director, Division of Substance Abuse, Depart- Robert Malcolm, M.D., Professor of Psychiatry, De-
ment of Psychiatric Medicine, East Carolina Univer- partment of Psychiatry and Behavioral Science, Med-
sity School of Medicine, Greenville, NC ical University of South Carolina, Charleston, SC

Edith S. Lisansky Gomberg, Ph.D., Professor of G. Alan Marlatt, Ph.D., Professor of Psychology, Di-
Psychology, Department of Psychiatry, University of rector, Addictive Behaviors Research Center, Addic-
Michigan Alcohol Research Center, Ann Arbor, MI tive Behaviors Research Center, University of Wash-
ington, Seattle, WA
Bridget F. Grant, Ph.D., Chief, Biometry Branch,
Division of Biometry and Epidemiology—National Barbara S. McCrady, Ph.D., Professor, Graduate
Institute on Alcohol Abuse and Alcoholism, School of Applied and Professional Psychology and
Bethesda, MD Department of Psychology; Clinical Director, Center
of Alcohol Studies, Rutgers University, Piscataway,
Robert Hendren, D.O., Director, Division of Child
NJ
and Adolescent Psychiatry, University of Medicine
and Dentistry of New Jersey, Robert Wood Johnson Jeffrey Merrill, Ph.D., Director for Economic Policy
Medical School, Piscataway, NJ and Research, Treatment Research Institute, Univer-
sity of Pennsylvania School of Medicine, Philadel-
Michie N. Hesselbrock, Ph.D., Professor, School of
phia, PA
Social Work, University of Connecticut, West Hart-
ford, CT William R. Miller, Ph.D., Regents Professor of Psy-
chology and Psychiatry, Department of Psychology,
Victor M. Hesselbrock, Ph.D., Professor of Psychia-
University of New Mexico, Albuquerque, NM
try, School of Medicine, University of Connecticut
Health Center, Farmington, CT Darlene H. Moak, M.D., Assistant Professor of Psy-
chiatry, Medical University of South Carolina, Insti-
Reid K. Hester, Ph.D., Director, Research Division,
tute of Psychiatry, Charleston, SC
Behavior Therapy Associates, Albuquerque, NM
Rudolf H. Moos, Ph.D., Research Career Scientist,
Harold D. Holder, Ph.D., Director and Senior Sci-
VA Palo Alto Health Care System, Center for Health
entist, Prevention Research Center, Berkeley, CA
Care Evaluation, Palo Alto, CA
James Huggins, Ph.D., B.C.D., Associate Director,
Theresa B. Moyers, Ph.D., Clinical Director, Sub-
Persad, Pittsburgh, PA
stance Abuse Treatment Program, VAMC Albuquer-
Ronald M. Kadden, Ph.D., Professor, Department que, Albuquerque, NM
of Psychiatry, University of Connecticut Health Cen-
Hugh Myrick, M.D., Assistant Professor of Psychia-
ter, Farmington, CT
try, Department of Psychiatry and Behavioral Sci-
Carolyn Kapner, M.S.W., L.S.W., Therapist, Per- ence, Medical University of South Carolina,
sad, Pittsburgh, PA Charleston, SC
 CONTRIBUTORS xvii

Joseph Nowinski, Ph.D., Associate Adjunct Professor Sidney H. Schnoll, M.D., Ph.D., Professor, Depart-
of Psychology, University of Connecticut, Storrs, CT ments of Internal Medicine and Psychiatry, Chair-
man, Division of Substance Abuse Medicine, Medi-
Charles P. O'Brien, M.D., Ph.D., Professor and
cal College of Virginia, Virginia Commonwealth
Vice Chair, Department of Psychiatry, University of
University, Richmond, VA
Pennsylvania, Chief of Psychiatry, VA Medical Cen-
ter, University of Pennsylvania, Treatment Research Timothy Sheehan, Ph.D., Executive Director, Re-
Center, Philadelphia, PA covery Services, Hazelden Foundation, Center City,
MN
Timothy J. O'Farrell, Ph.D., Associate Professor of
Psychology, Harvard Families and Addiction Pro- Pamela M. Skerker, R.N., M.S., Psychiatric Nurse
gram, Harvard Medical School Department of Psy- Practitioner, Department of Psychiatry, University of
chiatry, Veterans Affairs Medical Center, Brockton Connecticut Health Center, Farmington, CT
and West Roxbury, MA John Slade, M.D., Professor of Clinical Medicine,
Patricia Owen, Ph.D., Director, Butler Center for University of Medicine and Dentistry of New Jersey,
Research and Learning, Hazelden Foundation, Cen- New Brunswick, NJ
ter City, MN Robert S. Stephens, Ph.D., Associate Professor, De-
Robert Pandina, Ph.D., Professor of Psychology, Di- partment of Psychology, Virginia Polytechnic Insti-
rector, Center of Alcohol Studies, Rutgers, The State tute and State University, Blacksburg, VA
University of New Jersey, Piscataway, NJ Susan M. Stine, M.D., Ph.D., Associate Professor,
Department of Psychiatry and Behavioral Neurosci-
Mary Ann Pentz, Ph.D., Associate Professor, De-
ences, Wayne State University School of Medicine,
partment of Preventive Medicine, Director, Center
Detroit, MI
for Prevention Policy Research, University of South-
ern California, Los Angeles, CA Virginia Stoffel, M.S., Associate Professor, Univer-
sity of Wisconsin—Milwaukee, School of Social Wel-
Rae Jean Proescholdbell, B.A., Graduate Research
fare, Milwaukee, WI
Assistant, Department of Psychology, Arizona State
University, Tempe, AZ Christine Timko, Ph.D., Health Science Specialist,
VA Palo Alto Health Care System, Center for Health
Lori A. Quigley, Ph.D., Research Manager, UCSF
Care Evaluation, Palo Alto, CA
Treatment Outcome Research Group, University of
California—San Francisco, San Francisco, CA David G. Warren, J.D., Executive Director, North
Carolina Governor's Institute on Alcohol and Sub-
Domingo Rodriguez, Vice President for Commu- stance Abuse, Professor, Department of Community
nity Health and Human Services, Chicanos por la and Family Medicine, Duke University Medical
Causa, Phoenix, AZ Center, Durham, NC
Susan J. Rose, Ph.D., Assistant Professor, University Michael F. Weaver, M.D., Assistant Professor of In-
of Wisconsin-Milwaukee, School of Social Welfare, ternal Medicine, Division of Substance Abuse Medi-
Milwaukee, WI cine, Virginia Commonwealth University/Medical
Richard N. Rosenthal, M.D., Associate Professor of College of Virginia, Richmond, VA
Psychiatry, Director, Division of Substance Abuse, Laurence Westreich, M.D., Assistant Clinical Pro-
Albert Einstein College of Medicine; Associate fessor of Psychiatry, New York University School of
Chairman, Department of Psychiatry, Beth Israel Medicine; Chief of Dual Diagnosis Program, Belle-
Medical Center, New York, NY vue Hospital, New York, NY
Dorothy J. Sandstrom, M.S., Project Coordinator, Carolina E. Yahne, Ph.D., Psychologist, Center on
Western Psychiatric Institute and Clinic, Pittsburgh, Alcoholism, Substance Abuse, and Addictions, Uni-
PA versity of New Mexico, Albuquerque, NM
Pilar M. Sanjuan, B.A., Graduate Fellow, Center of Allen Zweben, D.S.W., Associate Professor, Univer-
Alcohol Studies, Rutgers, The State University of sity of Wisconsin-Milwaukee, School of Social Wel-
New Jersey, Piscataway, NJ fare, Milwaukee, WI
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 ADDICTIONS

A COMPREHENSIVE GUIDEBOOK
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 Introduction

Barbara S. McCrady
Elizabeth E. Epstein

If we could sniff or swallow something that would, for five or six hours each day, abolish our
solitude as individuals, atone us with our fellows in a glowing exaltation of affection and make
life in all its aspects seem not only worth living, but divinely beautiful and significant, and if
this heavenly, world-transfiguring drug were of such a kind that we could wake up next morning
with a clear head and an undamaged constitution—then, it seems to me, all our problems (and
not merely the one small problem of discovering a novel pleasure) would be wholly solved and
earth would become paradise.
Aldous Huxley, 1949

Aldous Huxley's romantic vision of substance use cal model of the time. Many models of addiction
stands in stark contrast to the serious problems have held the view that abstinence is necessary to
caused by substance use in the late 20th century. successful control of the addiction:
Substance use in the United States claims close to
600,000 lives per year, including approximately If an addict who has been completely cured starts
440,000 attributable to nicotine use, 125,000 from smoking again he no longer experiences the dis-
alcohol use, and 10,000 from heroin and cocaine use comfort of his first addiction. There exists, there-
fore, outside alkaloids and habit, a sense for
(exclusive of deaths from HIV). Alcohol, tobacco,
opium, an intangible habit which lives on, de-
and other drug use and abuse are interwoven into spite the recasting of the organism. . . . The dead
many of the most pressing of our societal ills, includ- drug leaves a ghost behind. At certain hours it
ing chronic illness, crime, violence, and homeless- haunts the house. (Cocteau, 1929)
ness. Concerns about the adverse effects of alcohol,
tobacco, and other drugs date back to biblical times: Contemporary thought, however, has introduced
"He shall separate himself from wine and strong the possibility that moderation is an appropriate goal
drink, and shall drink no vinegar of wine, or vinegar for the substance abuser, either as an interim goal to
of strong drink, neither shall he drink any liquor of engage an individual in treatment, or as a long-term
grapes, nor eat moist grapes, or dried" (Bible Num- goal. Data on long-term use patterns of alcohol- and
bers 6:3). drug-abusing and -dependent individuals suggest that
Models of addiction have varied throughout his- lifelong abstinence is an uncommon outcome: Most
tory, and different treatment approaches have pre- individuals experience fluctuating periods of modera-
dominated, corresponding to the prevailing theoreti- tion, abstinence, and heavy or problem use. Conse-

3
4 INTRODUCTION

quently, many professionals in the public health and the authors have been successful in achieving this
clinical realm now embrace a harm reduction ap- difficult balance.
proach to minimize or decrease the adverse conse- The chapters are organized according to consis-
quences of use. tent themes within each section to facilitate compa-
Despite a rich and varied history of and literature rability of topics across chapters. Part I (chapters 1-3)
on alcohol, tobacco, and other drugs, science has provides a broad background about substance use:
come lately to the field. The National Institute on epidemiology, current models of and knowledge
Alcohol Abuse and Alcoholism (NIAAA) was estab- about etiology, and information about the course in
lished in 1971; the National Institute on Drug Abuse both treated and community samples. Part II (chap-
(NIDA), in 1973. Since the establishment of these ters 4-10) covers pharmacological and clinical infor-
two federal agencies, alcohol, tobacco, and other mation about major drug classes, including basic
drugs have become increasingly legitimate topics of knowledge about each drug class, its metabolism,
inquiry for scientists and targets for clinical care by and its neuropharmacology as well as clinical infor-
health care professionals. Today, we have an impres- mation such as preparations, street names, symptoms
sive body of knowledge of the epidemiology, etiology, of intoxication, dependence, and withdrawal.
neuropharmacology, assessment, treatment, and pre- Parts III, IV, and V provide core material for the
vention of substance use disorders. In all areas of practitioner. In part III (chapters 11-12), chapter 11
health care delivery, professionals are being required provides a comprehensive overview of approaches to
to acquire and demonstrate mastery of the core assessment and measures, while chapter 12 focuses
knowledge in this field. Many professions now offer on treatment planning and decision making. Part IV
specialty credentialing in the substance use field, and (chapters 13-21) provides descriptions of a range of
alcohol and drug counseling is becoming an increas- models of treatment that have empirical support for
ingly regulated field. their efficacy and includes detailed information on
Our goal in developing this volume was to create historical origins, theory, therapeutic change, and
a resource for several audiences. First, health care empirical support for each approach. Part IV con-
professionals and professionals in training in psychol- cludes with a summary chapter that highlights major
ogy, medicine, social work, nursing, and counseling psychological and pharmacological approaches to
will find the volume invaluable. As a training guide, treatment. Part V (chapters 22-24) focuses on addi-
for instance, the book covers material useful for cre- tional issues of direct concern to the practitioner: le-
dentialing exams, such as that required by the Ameri- gal and ethical matters, credentialing, and the com-
can Psychological Association College of Profes- plex interface between the treatment of substance
sional Psychology Certificate of Proficiency in the use and other social and health care systems.
Treatment of Alcohol and Other Psychoactive Sub- Part VI (chapters 25-29) shifts attention from
stance Use Disorders. The book is also suitable for models of care to target populations. Authors in this
scientists who would want easy access to a breadth of section contributed chapters that review the best cur-
knowledge in the field that would complement the rent knowledge about alcohol, tobacco, and other
specialized knowledge they have in their own area of drug abuse in a range of populations: those with con-
inquiry. comitant psychiatric disorders, age-limited popula-
The volume is intended to be comprehensive yet tions (youth and the elderly), racial and ethnic mi-
manageable, accessible yet scholarly. In outlining nority groups, women, and gay men and lesbians.
the sections of the book, we attempted to include Part VII (chapters 30-32) turns to the prevention
chapters on all aspects of substance abuse/depen- and economics of substance use. The prevention
dence that a typical practitioner might need to be chapters (30 and 31) describe strategies that target
familiar with to understand and treat addictive disor- both the individual and the environment; the eco-
ders. In outlining each chapter, we envisioned nei- nomics chapter (chapter 32) considers the larger
ther a case-study-based "how-to" approach nor an ar- context of the health economics of substance abuse
cane review of scientific knowledge. Rather, each treatment.
author strove to strike a balance, to write a chapter The reader may use the volume in three distinct
that provides the best scientific knowledge, but in a ways: (1) As a textbook, the volume provides an or-
format that is accessible and useful. We believe that derly and comprehensive survey, suitable for a gradu-
 INTRODUCTION 5

ate course on the assessment and treatment of the from experience. We hope that this volume will pro-
abuse of alcohol, tobacco, and other drugs. The text- vide you, the reader, with a firm grounding in cur-
book reader should begin at the beginning and read rent knowledge and clinical methods that will stimu-
through the entire volume. (2) When the book is late you to contribute to this exciting and evolving
used as a resource for treatment planning, the reader field.
should first look to specific chapters relevant to the
presenting drug(s) of abuse and the treatment popu- References
lation and should then use the index to identify as-
sessment devices and treatment models related to the Cocteau, Jean. Opium. (1929). Cited in Columbia Dic-
tionary of Quotations. New York: Columbia Univer-
specific drug(s) of interest. (3) To use the book as a
sity Press.
reference volume, the reader can find answers to spe-
Huxley, Aldous. (1949). Wanted, a new pleasure. In
cific questions in both the specific chapters and the Music at Night and Other Essays. Cited in Colum-
index. bia Dictionary of Quotations. New York: Columbia
Knowledge evolves, both from the laboratory and University Press.
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 I

Epidemiology, Etiology, and Course

of Substance Use Disorders
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 1

Alcohol and Drug Use, Abuse, and

Dependence: Classification,
Prevalence, and Comorbidity
Bridget F. Grant
Deborah A. Dawson

This chapter provides an epidemiological context for sion of various approaches to subtyping alcohol and
the remainder of this volume by describing the mag- drug use disorders. Attempts to classify alcohol and
nitude of the alcohol and drug problem in the drug use disorders have been problematic both con-
United States. It also presents the most recent na- temporarily and historically. Although the lack of
tional statistics on alcohol and drug use, abuse and consensus is not unique to the alcohol and drug
dependence, and comorbidity between alcohol, drug, fields, there currently exists no consensus on how to
and psychiatric disorders. Emphasis is placed on the classify alcohol and drug use disorders, and no such
summary of data from general population surveys, consensus is expected in the near future. Historical
because prevalence statistics derived from treated changes in these classification systems also adversely
samples are not representative and are subject to affect the collection and communication of accurate
unique selection biases. Moreover, individuals in public health statistics over time. This chapter's dis-
treatment are more likely to have multiple disor- cussion of changes in classification systems over time
ders than are individuals in the general population, and the differences and similarities among alterna-
thus spuriously inflating estimates of the prevalence tive systems is intended to help researchers and clini-
of comorbidity and distorting the relationships exist- cians gauge the degree to which current and future
ing between alcohol, drug, and other psychiatric dis- research findings can be integrated with one another
orders. and with results from earlier studies using historical
Preceding the prevalence and comorbidity statis- classification systems. Only in this way can scientific
tics is a historical overview of classification systems knowledge in the alcohol and drug fields be ad-
in the alcohol and drug fields that includes a discus- vanced.

9
10 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

CLASSIFICATION OF ALCOHOL jor category for intoxication psychosis but placed pri-
AND DRUG USE DISORDERS: mary emphasis on organic disorders associated with
HISTORICAL OVERVIEW chronic alcoholism.
It was not until the early 1960s that classification
Up until the early 1800s, the classification of alcohol systems began to give some consideration to alcohol
and drug use disorders received very little attention. and drug use problems that did not involve addiction
At the institutional level, early official efforts at classi- or dependence. The most well known of these classi-
fication can be seen in 19th-century asylum records ficatory systems was outlined by Jellinek (1960) in
in which terms such as delirium tremens, insanity his classical work, "The Disease Concept of Alcohol-
caused by intemperance, and dipsomania (drink seek- ism." In his classification, Jellinek clearly differenti-
ing) were used to describe conditions resulting from ated varieties of alcohol use disorders that involved a
alcohol use. In France, the statistical classification clear dependence process (gamma and delta types)
used throughout the 19th century to record morbid- from those that did not (alpha, beta, and epsilon
ity and mortality included alcohol-related rubrics types). It was not until the third edition of the Diag-
such as habitual drinking and socially induced heavy nostic and Statistical Manual of Mental Disorders
drinking (Babor, 1992). (DSM-III; American Psychiatric Association [APA],
Beginning in the early 19th century, a series of 1980) and the eighth revision of the International
medical writers began to lay the groundwork for what Classification of Diseases (ICD-8; World Health Or-
would eventually become the disease concept of al- ganization [WHO], 1968) that nondependent sub-
coholism. Among these early contributors was Bruhl- stance use disorders were introduced.
Cramer, who in 1819 introduced the concept of In the ICD-8, alcohol addiction was character-
drink seeking, or dipsomania. Esquirol (1845) was ized by a state of physical and emotional dependence
the first to give drunkenness or monomania a place on regular or periodic heavy and uncontrolled alco-
in psychiatric nomenclatures, and Huss (1849) was hol consumption during which a person experiences
first to use the term alcoholism. By the latter part of a compulsion to drink and withdrawal symptoms
the 19th century, Carpenter (1850), Crothers (1893), upon cessation of drinking.The categories of episodic
Kerr (1888), and McBride (1910) had promulgated and habitual excessive drinking, which were not ex-
the disease concept of inebriety as a concept very tended to other drugs, focused on pathological drink-
similar to what is referred to today as dependence. ing patterns and were differentiated from alcohol
In this formulation, inebriety and dipsomania were addiction by the absence of compulsion and with-
diseases, and their presumed origin was biological or drawal. The alcohol and drug abuse and dependence
possibly genetic. categories of the DSM-III were characterized by pat-
Although the early nosological history of drug use terns of pathological use, and by impairment in so-
disorders is more vague than that of alcohol use cial or occupational functioning due to use, with de-
disorders, it is likely that the first attempts at their pendence additionally requiring the presence of
classification occurred during the early drug epi- either tolerance or withdrawal.
demics of the late 19th century. At that time, addic- In 1976, Edwards and Gross developed the con-
tion to opiates and cocaine gave rise to terms such cept of the alcohol dependence syndrome (ADS).
as morphism and narcomania. These terms were The concept of the ADS was to become extremely
used in much the same way as inebriety and dipsoma- influential in the formation of all further revisions of
nia had been used to describe dependence on al- the /CD and DSM definitions of both alcohol and
cohol. drug use disorders. The syndrome was provisionally
With the disease concept firmly entrenched by endowed with the following seven elements: (1) nar-
the end of the 19th century, diagnostic classifications rowing of the drinking repertoire; (2) salience of
for the next 50 years would continue to emphasize drink-seeking behavior; (3) increased tolerance to al-
the concepts of addiction or dependence, giving very cohol; (4) repeated withdrawal symptoms; (5) relief
little attention to the social, psychological, and medi- or avoidance of withdrawal by further drinking; (6)
cal consequences of substance intoxication and subjective awareness of compulsion to drink; and (7)
chronic use. This trend began with Kraeplin (1909- rapid reinstatement of symptoms after a period of ab-
1915), whose Textbook of Psychiatry included a ma- stinence.
 CLASSIFICATION, PREVALENCE, AND COMORBIDITY 11

The ADS was described not as an all-or-none dis- ence how substance use relates to legal or social con-
ease state, but as a condition which existed in de- sequences, respectively.
grees of severity with the emphasis squarely placed Although the ICD-10 and DSM-IV classifications
on dimensionality of a learned phenomenon. Not all of alcohol and drug use disorders do mirror many of
components of the syndrome needed always to be the structural aspects of the ADS, they do not accept
present in the same intensity. More important, the the learning theory underlying it. The DSM-III,
unidimensional ADS was kept theoretically distinct DSM-II-R, and DSM-IV classifications were claimed
from other alcohol-related disabilities in what Ed- to be largely atheoretical, as were the corresponding
wards and his colleagues (Edwards, Gross, Keller, ICD classifications. (However, the DSMs have been
Moser, & Room, 1977) termed the biaxial concept. criticized by social and behavioral scientists for fail-
Alcohol- and drug-related physical, mental, and so- ing to explicate the underpinnings of their nomen-
cial problems were recognized as public health con- clature, even though it is clear that their classifica-
cerns that were significant in their own right, quite tions entail both ontological and epistemological
apart from dependence. assumptions arising from a medical model.) Rather,
The ADS concept's impact on the current ICD- the DSM authors' claims of an atheoretical classifica-
10 and DSM-IV is evident (table 1.1). In both these tion would seem to have been adopted to minimize
definitions, the syndromal and dimensional compo- opposition from other health professions concerned
nents of the ADS are present in addition to the differ- about the medicalization of the mental health field.
entiation of the dependence category from nonde- Over the past 30 years, behavioral scientists have
pendent categories of abuse and harmful use (table proposed an alternative approach to the disease con-
1.2). Both classifications also share much of the con- cept of alcohol and drug dependence that underlies
tent of their diagnostic criteria with those of the the DSM classifications (Adesso, 1995; Nathan, 1981;
ADS. Changes that occurred with the ninth revision Pattison, Sobell, & Sobell, 1977). In this approach,
of the ICD (ICD-9; WHO, 1978) and the third edi- alcohol and drug use disorders are viewed not as uni-
tion, revised, of the DSM (DSM-III-R; APA, 1987) tary disorders defined in terms of a single disease
and that were retained in the tenth revision of the label, but as acquired habits that emerge from bio-
ICD (ICD-10; WHO, 1992) and fourth edition of logical, pharmacological and conditioning factors.
the DSM (DSM-IV; APA, 1994) also included the Drinking behavior occurs on a continuum of sever-
adoption of the same criteria for abuse, harmful use, ity, and excessive drinking occurs on a continuum
and dependence across all psychoactive substances. with normal drinking. Emphasis is placed on envi-
More important, the earlier defining criteria of com- ronmental, affective, and cognitive antecedent condi-
pulsion, tolerance, and withdrawal were retained— tions and on reinforcing consequences of drinking.
but were no longer required—for a dependence di- The goal of this functional approach is a classifica-
agnosis in either the ICD-10, the DSM-IV, or their tion of pathological drinking that is governed by uni-
immediate predecessors. versal principles of human motivation and learning
Although many subtle differences exist between that guide us all (Wulfert, Greenway, & Dougher,
the current ICD and DSM formulations of alcohol 1996).
and drug use disorders, one important difference is
worth noting. In the ICD-10, the harmful use cate-
gory is characterized by actual physical or psycholog- SUBTYPES OF ALCOHOL AND
ical harm to the user, whereas the DSM-IV abuse DRUG USE DISORDERS
category additionally includes social, legal, and occu-
pational consequences of use. Because cultural con- From as early as the mid-19th century, clinicians and
text is an important determinant of substance use researchers recognized that individuals classified as
patterns and consequences, it can be expected that alcoholics or as alcohol-dependent were far from ho-
the inclusion of social and legal problems in the mogeneous. Babor and Lauerman (1986) cited the
DSM-IV will reduce the cross-cultural applicability development of 39 different classifications of alco-
of the abuse category. For example, changes in legal holic subtypes between 1850 and 1941. Although
definitions or controls and differences between cul- these early typologies were unsystematic and lacking
tural mores of various countries will markedly influ- in empirical foundation, they helped to identify de-
 TABLE 1.1 DSM-/V and ICD-10 Diagnostic Criteria for Alcohol and Drug Dependence

DSM-/V ICD-IO

Clustering criterion A. A maladaptive pattern of substance use, A. Three or more of the following have
leading to clinically significant impair- been experienced or exhibited at some
ment or distress as manifested by three time during the previous year:
or more of the following occurring at
any time in the same 12-month period:
Tolerance (1) Need for markedly increased (1) Evidence of tolerance, such that in-
amounts of a substance to achieve creased doses are required in order
intoxication or desired effect; or to achieve effects originally pro-
markedly diminished effect with duced by lower doses
continued use of the same amount
of the substance
Withdrawal (2) The characteristic withdrawal syn- (2) A physiological withdrawal state
drome for a substance or use of a when substance use has ceased or
substance (or a closely related sub- been reduced as evidenced by: the
stance) to relieve or avoid with- characteristic substance withdrawal
drawal symptoms syndrome, or use of substance (or a
closely related substance) to relieve
or avoid withdrawal symptoms
Impaired control (3) Persistent desire or one or more un- (3) Difficulties in controlling substance
successful efforts to cut down or use in terms of onset, termination,
control substance use or levels of use
(4) Substance use in larger amounts or
over a longer period than the per-
son intended
Neglect of activities (5) Important social, occupational, or (4) Progressive neglect of alternative
recreational activities given up or re- pleasures or interests in favor of sub-
duced because of substance use stance use; or
Time spent (6) A great deal of time spent in activi- A great deal of time spent in activi-
ties necessary to obtain, to use, or ties necessary to obtain, to use, or to
to recover from the effects of sub- recover from the effects of sub-
stance used stance use
Inability to fulfill roles None None
Hazardous use None None
Continued use despite (7) Continued substance use despite (5) Continued substance use despite
problems knowledge of having a persistent or clear evidence of overtly harmful
recurrent physical or psychological physical or psychological conse-
problem that is likely to be caused quences
or exacerbated by use
Compulsive use None (6) A strong desire or sense of compul-
sion to use substance
Duration criterion B. No duration criterion separately speci- B. No duration criterion separately speci-
fied. However, several dependence crite- fied
ria must occur repeatedly as specified
by duration qualifiers associated with
criteria (e.g., "often," "persistent," "con-
tinued")
Criterion for subtyping With physiological dependence: Evi- None
dependence dence of tolerance or withdrawal (i.e.,
any of items A(l) or A(2) above are
present)
Without physiological dependence: No
evidence of tolerance or withdrawal
(i.e., none of items A(l) or A(2) above
are present)
 CLASSIFICATION, PREVALENCE, AND COMORBIDITY 13

TABLE 1.2 DSM-IV and ICD-JO Diagnostic Criteria for Alcohol and Drug Abuse/Harmful Use

DSM-IV Alcohol and Drug Abuse

A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one
(or more) of the following occurring within a 12-month period:
(1) recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home
(2) recurrent substance use in situations in which use is physically hazardous
(3) recurrent substance-related legal problems
(4) continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacer-
bated by the effects of alcohol
B. The symptoms have never met the criteria for substance dependence for the same class of substance.
ICD-10 Harmful Use of Alcohol and Drugs
A. A pattern of substance use that is causing damage to health. The damage may be physical or mental. The diagnosis
requires that actual damage should have been caused to the mental or physical health of the user.
B. No concurrent diagnosis of the substance dependence syndrome for same class of substance.

fining characteristics, such as drinking patterns, fam- is characterized as occurring primarily among men
ily history of alcoholism, personality characteristics, and is associated with an early onset of alcoholism, a
and psychopathologies, that have served as the basis high level of familial alcoholism among male rela-
for subsequent alcoholism typologies (Babor, 1996). tives (i.e., a primarily endogenous etiology), high lev-
In 1941, Bowman and Jellinek synthesized a number els of antisocial activity and novelty seeking, and low
of earlier typologies into a classification scheme that levels of harm avoidance (Cloninger, 1987; Clon-
defined four types of alcoholics on the basis of their inger et al., 1981).
drinking patterns (continuous, periodic, or irregular) Babor and associates (1992) used the technique
and etiology (endogenous or exogenous). These cate- of cluster analysis to identify 17 defining characteris-
gories were later superseded by Jellinek's (1960) far tics that distinguished their proposed categories of
more widely recognized categories of alpha, beta, Type A and Type B alcoholism. They found that of
gamma, delta, and epsilon alcoholism. Of these, Jel- the two groups, Type B alcoholics had a greater ge-
linek regarded only the gamma and delta varieties as netic predisposition toward alcoholism, more child-
conforming to the disease concept of alcoholism and hood risk factors such as conduct disorder, an earlier
distinguished these by more endogenous influences, onset of alcoholism, more severe symptoms of depen-
more rapid progression, and greater loss of control dence, more polydrug use, more psychopathology
among gamma alcoholics, and more exogenous in- and life stress, and a more chronic treatment his-
fluences, slower progression, and greater inability to tory. Subsequent attempts to replicate this dichotomy
abstain among delta alcoholics. and extend it to substances other than alcohol have
More recent alcohol typologies have refined these yielded different results in terms of which of the de-
categories and added new defining characteristics, fining characteristics contribute most strongly to the
but the most well known of the current subtypes Type A-Type B distinction, but medical conditions,
have maintained the distinction between two broad dependence severity, and lifetime severity have been
categories of alcoholics. For example, Cloninger, repeatedly identified as among the most important
Bohman, and Sigvardsson (1981) proposed a Type dimensions (Ball, 1996; Schuckit et al., 1995).
1 versus Type 2 distinction. Type 1 (milieu-limited) Although each new classification scheme has been
alcoholism is hypothesized to affect both men and based on modifications of existing subtypes, the simi-
women, to have a relatively late onset, to be influ- larities among the typologies are more striking than
enced by both endogenous and exogenous factors, to their differences. Babor (1996) argued that the di-
involve relatively mild alcohol problems with little chotomy between what he terms the Apollonian and
antisocial activity, and to be associated with low lev- Dionysian types of alcoholism captures not only the
els of novelty seeking and high levels of harm avoid- delta-gamma, Type 1-Type 2, and Type A-Type B
ance. In contrast, Type 2 (male-limited) alcoholism distinctions but also many of the other typologies that
14 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

have been proposed during the last century, includ- Longitudinal Alcohol Epidemiologic Survey (NLAES),
ing the reactive versus essential and symptomatic a nationwide household survey sponsored by the Na-
subtypes (Knight, 1938), the family history negative tional Institute on Alcohol Abuse and Alcoholism
versus positive dichotomy (Frances, Timm, & Buckey, (Grant et al., 1994). The NLAES consisted of a rep-
1980), affiliative versus schizoid drinkers (Morey & resentative sample of the U.S. population involving
Skinner, 1986), developmentally cumulative versus direct face-to-face interviews with 42,862 respon-
antisocial and negative affect drinkers (Zucker, 1987), dents, 18 years of age and older. The sampling de-
and the late- versus early-onset dichotomy (Buydens- sign included clustering and stratification with the
Branchey, Branchey, & Noumair, 1989). Future re- provisions for oversampling blacks and young adults
search will undoubtedly continue to clarify the dis- (aged 18-29).
tinctions that characterize these two broad categories Data from the NLAES indicated that two thirds
of alcoholism, to test the applicability of these cate- (66.0%) of adults 18 years of age and over were life-
gories to different drugs and within different subpop- time drinkers who had consumed at least 12 alco-
ulations, and to extend their usefulness as predictors holic drinks during any 1 year of their lives, and
of response to different types of treatment. nearly half (44.4%) were past year drinkers who had
Some of the typologies of alcohol dependence de- consumed 12 or more drinks in the year preceding
scribed above have been tested for their applicability the interview (table 1.3). Drinking was more com-
to other substances. Wills, Vaccaro, and McNamara mon among men than women with the gender dif-
(1994) examined substance use and personality char- ferential strongest among blacks and was more com-
acteristics in a sample of 457 adolescents 12 to 15 mon among nonblacks (including whites and all
years of age. Cluster analysis resulted in five distinct other races) than blacks with the racial differential
groups. The two groups with the highest levels of strongest among women. The prevalence of lifetime
novelty seeking and lowest levels of harm avoidance drinking was highest (73.3%) for individuals in the
and reward dependence were also those with the age range of 30-44 years and lowest (47.8%) for
highest levels of cannabis use. Wills et al. interpreted those aged 65 years and older. The prevalence of
these results as consistent with the Typel-Type 2 dis- past-year drinking was marginally higher for persons
tinction, the adolescents in these two groups corre- aged 18-29 than for those aged 30-44 (53.4% versus
sponding to the Type 2 subtype. The construct, con- 50.2%) and declined sharply in the older age groups
current, and predictive validity of the Type A-Type to 40.5% for persons aged 45-64 and 24.5% for those
B distinction has been supported in a cluster analysis aged 65 years and older.
of 399 cocaine users that included both those seek- Heavy drinking may be defined in terms of drink-
ing and those not seeking treatment (Ball, Carroll, ing patterns (e.g., the frequency of drinking five or
Babor, & Rounsaville, 1995), and some but not all more, or some other number of, drinks) or in terms
of the characteristics distinguishing these two sub- of volume of ethanol intake. Among volume-based
types were replicated in samples of cannabis and opi- measures, an average daily intake of more than 1
ate users (Feingold, Ball, Kranzler, & Rounsaville, ounce of ethanol (the equivalent of more than two
1996). Other typologies that have been proposed for standard drinks) frequently has been used as a thresh-
drug abuse and dependence include Cancrini's old for heavy drinking (Williams & Debakey, 1992).
(1994) fourfold classification based on underlying By this measure, nearly one quarter (23.4%) of U.S.
psychopathology (adjustment disorders, neurotic dis- adults were lifetime heavy drinkers, that is, they
orders, psychosis/borderline disorders, and socio- drank an average of more than 1 ounce of ethanol
pathic personality disorders) and the distinction be- per day during their period of heaviest drinking (but
tween recreational users and self-medicators that is not necessarily throughout their entire lives). Thus,
based on underlying motivation (Carlin & Strauss, slightly more than one third of all lifetime drinkers
1978). could be defined as heavy drinkers at some point
during their drinking histories. In contrast, the preva-
PREVALENCE OF ALCOHOL lence of past-year heavy drinking was only 8.7%, less
AND DRUG USE than one fifth of past-year drinkers.
The prevalence of heavy drinking was higher
Prevalence figures on alcohol and drug use pre- among men than women and higher among non-
sented in this chapter are based on the 1992 National blacks than blacks. With respect to age, the preva-
TABLE 1.3 Prevalence (%) of Lifetime and Past-Year Alcohol Use3 and
Heavy Use, by Gender, Ethnicity, and Age

Alcohol use3 Heavy use"

Sociodemographic
characteristic Lifetime Past year Lifetime Past year

Total 66.0 44.4 23.4 8.7

18-29 68.0 53.4 25.3 11.2
30-44 73.3 50.2 27.2 8.4
45-64 66.1 40.5 23.0 8.9
65+ 47.8 24.5 13.0 5.2
Total men 78.3 55.8 35.6 13.7
18-29 75.7 64.2 34.8 17.1
30-44 82.8 60.8 39.7 13.1
45-64 80.3 51.0 36.8 13.5
65+ 68.2 36.4 25.0 9.1
Total women 54.7 33.9 12.1 4.1
18-29 60.4 42.6 15.7 5.3
30-44 63.9 39.8 15.0 3.8
45-64 52.8 30.7 10.3 4.5
65+ 33.4 16.1 4.8 2.4
Total nonblack 67.9 45.9 24.1 8.8
18-29 71.7 56.4 27.2 11.5
30-44 75.3 51.7 28.1 8.4
45-64 67.3 41.7 23.3 9.1
65+ 48.7 25.7 13.2 5.4
Nonblack men 79.6 56.9 36.5 13.7
18-29 77.9 66.1 36.4 17.2
30-44 84.2 62.0 40.8 13.0
45-64 80.9 51.8 37.0 13.7
65+ 68.9 37.6 25.0 9.4
Nonblack women 56.9 35.6 12.6 4.2
18-29 65.3 46.5 17.6 5.7
30-44 66.4 41.4 15.3 3.7
45-64 54.3 32.1 10.3 4.7
65+ 34.2 17.2 5.0 2.6
Total black 51.4 32.5 17.5 7.7
18-29 45.1 34.5 13.5 9.0
30-44 58.7 39.1 21.1 8.8
45-64 55.0 30.1 20.8 7.1
65+ 37.9 11.7 11.0 2.4
Black men 67.6 46.6 28.6 13.3
18-29 60.5 50.9 23.4 16.2
30-44 71.8 51.3 30.9 14.3
45-64 74.0 43.5 34.1 11.8
65+ 59.6 22.7 23.9 4.6
Black women 38.3 21.2 8.7 3.3
18-29 32.2 20.8 5.3 3.1
30-44 47.7 28.8 12.9 4.3
45-64 39.8 19.4 10.0 3.4
65+ 24.0 4.8 3.2 1.0
Note. Data compiled from Source and accuracy statement for the National Longitudinal Alcohol
Epidemiologic Survey. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism.
"Consumption of 12 or more drinks within a 12-month period.
b
Average daily consumption of more than 1.0 ounce of ethanol.
16 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

lence of lifetime heavy drinking generally was of commonly used drug (13.9%), followed by illicit use
about the same magnitude for all ages under 65 of prescription drugs (6.2% for all types combined,
years, with lower rates among persons 65 years and including 2.2% for sedatives, 2.4% each for opioids
older. Among nonblack women, though, the rates of and tranquilizers, and 4.1% for amphetamines) and
lifetime heavy drinking were lower for those aged cocaine or crack (3.7%). Lifetime use of hallucino-
45-64 than for those aged 18-29, and the opposite gens was reported by 2.0% of all adults. Considering
was true among black men and women. Past-year all types of drugs combined, the lifetime prevalence
heavy drinking was equally common among persons of use was higher for men than women (23.0% vs.
aged 45-64 and those aged 30-44, the highest preva- 13.2%), higher for individuals aged 18-29 than for
lence being found among those aged 18-29. those aged 30 and older (26.3% vs. 17.1%, with a
Table 1.4 shows the lifetime prevalence of illicit smaller age differential for blacks than for non-
drug use, that is, the use of drugs at least 12 times blacks), and slightly higher for nonblacks than blacks
without or beyond the limits of a doctor's prescrip- (16.0% vs. 12.4%, with most of the difference occur-
tion. Overall, 15.6% of U.S. adults reported a positive ring among individuals aged 18-29). These patterns
lifetime history of drug use. Cannabis was the most held true for most of the individual types of drugs

TABLE 1.4 Prevalence (%) of Lifetime Illicit Use of Selected Types of Drugs, by Gender,
Ethnicity, and Age

Prescription drugs

Sociodemographic Any Tranquil- Amphet- Hallu-

characteristic drug Total Sedatives Opioids izers amines Cannabis cinogens Cocaine

Total 15.6 6.2 2.2 2.4 2.4 4.1 13.9 2.0 3.7
18-29 23.0 8.4 2.6 3.6 3.2 5.8 21.1 3.4 5.6
30+ 13.2 5.4 2.1 2.0 2.2 3.6 11.5 1.5 3.1
Total men 19.5 7.5 3.0 3.2 3.2 5.4 18.0 3.0 5.0
18-29 26.3 8.7 3.1 4.2 3.6 6.4 25.0 4.7 6.5
30+ 17.1 7.1 2.9 2.8 3.0 5.0 15.5 2.5 4.5
Total women 12.0 4.9 1.6 1.7 1.8 3.0 10.1 1.0 2.6
18-29 19.8 8.1 2.1 2.9 2.7 5.3 17.2 2.1 4.7
30+ 9.6 4.0 1.4 1.3 1.4 2.3 7.9 0.7 1.9
Total nonblack 16.0 6.5 2.4 2.5 2.6 4.5 14.3 2.2 3.8
18-29 24.4 9.3 2.8 3.9 3.6 6.6 22.4 3.8 6.0
30+ 13.4 5.7 2.2 2.1 2.3 3.8 11.7 1.7 3.1
Nonblack men 19.8 7.9 3.1 3.3 3.4 5.7 18.2 3.3 5.1
18-29 27.2 9.5 3.3 4.5 4.0 7.1 25.8 5.2 6.9
30+ 17.2 7.4 3.0 2.9 3.2 5.3 15.6 2.6 4.5
Nonblack women 12.5 5.3 1.7 1.7 1.8 3.3 10.6 1.2 2.7
18-29 21.5 9.0 2.3 3.2 3.1 6.1 18.8 2.3 5.2
30+ 9.8 4.1 1.5 1.3 1.5 2.5 8.2 0.8 1.9
Total black 12.4 3.3 1.1 1.6 1.4 1.4 10.9 0.6 3.0
18-29 14.6 2.8 1.0 1.7 0.8 0.9 13.0 0.9 2.9
30+ 11.4 3.6 1.2 1.6 1.7 1.6 9.9 0.5 3.0
Black men 17.4 4.1 1.7 1.8 1.7 2.2 16.3 1.1 4.2
18-29 20.1 3.2 1.4 2.0 1.1 1.3 18.9 1.4 4.2
30+ 16.2 4.5 1.8 1.7 2.0 2.6 15.2 1.0 4.2
Black women 8.3 2.7 0.7 1.4 1.2 0.8 6.4 0.2 2.0
18-29 10.0 2.5 0.6 1.5 0.5 0.7 8.1 0.5 1.9
30+ 7.6 2.9 0.7 1.4 1.4 0.8 5.8 0.1 2.0
Note. Data compiled from Source and accuracy statement for the National Longitudinal Alcohol Epidemiologic Survey. Rockville, MD: Na-
tional Institute on Alcohol Abuse and Alcoholism.
 CLASSIFICATION, PREVALENCE, AND COMORBIDITY 17

TABLE 1.5 Prevalence (%) of Past-Year Illicit Use of Selected Types of Drugs, by Gender,
Ethnicity, and Age

Prescription drugs

Sociodemographic Any Tranquil- Amphet- Hallu-

characteristic drug Total Sedatives Opioids izers amines Cannabis cinogens Cocaine

Total 4.9 1.5 0.2 0.6 0.5 0.4 3.9 0.3 0.6
18-29 10.7 3.0 0.4 1.2 0.9 1.3 9.3 1.0 1.3
30+ 3.0 1.0 0.2 0.4 0.4 0.2 2.2 <0.1 0.4
Total men 6.4 1.5 0.2 0.6 0.6 0.5 5.5 0.4 0.9
18-29 13.2 2.9 0.4 1.2 0.9 1.5 12.1 1.4 1.7
30+ 4.0 1.0 0.1 0.5 0.5 0.2 3.1 0.1 0.5
Total women 3.6 1.4 0.3 0.6 0.5 0.4 2.5 0.1 0.4
18-29 8.2 3.0 0.4 1.3 0.9 1.2 6.4 0.6 0.8
30+ 2.1 0.9 0.2 0.4 0.5 0.1 1.3 <0.1 0.2
Total nonblack 4.9 1.5 0.2 0.6 0.5 0.5 4.0 0.3 0.5
18-29 11.2 3.2 0.5 1.3 1.0 1.5 9.7 1.1 1.3
30+ 2.9 1.0 0.2 0.4 0.4 0.2 2.1 0.1 0.3
Nonblack men 6.3 1.6 0.2 0.7 0.6 0.6 5.4 0.5 0.8
18-29 13.5 3.2 0.4 1.3 0.9 1.7 12.4 1.6 1.8
30+ 3.8 1.1 0.1 0.5 0.5 0.2 3.0 0.1 0.5
Nonblack women 3.6 1.5 0.3 0.6 0.5 0.4 2.6 0.2 0.3
18-29 8.8 3.3 0.5 1.4 1.0 1.4 7.0 0.7 0.8
30+ 2.0 0.9 0.2 0.4 0.4 0.2 1.3 <0.1 0.2
Total black 4.7 1.0 0.1 0.5 0.4 <0.1 3.8 0.1 1.0
18-29 7.3 1.3 0.1 0.6 0.5 <0.1 6.5 0.2 1.0
30+ 3.6 0.9 0.1 0.4 0.4 <0.1 2.7 0.0 1.0
Black men 6.9 0.9 0.1 0.4 0.4 <0.1 6.0 0.2 1.4
18-29 10.8 1.4 0.1 0.4 0.9 <0.1 10.4 0.5 1.4
30+ 5.1 0.7 0.1 0.4 0.3 <0.1 4.1 0.0 1.4
Black women 3.0 1.1 0.1 0.6 0.4 <0.1 2.1 0.0 0.7
18-29 4.4 1.2 0.1 0.9 0.2 <0.1 3.3 0.0 0.7
30+ 2.4 1.0 0.1 0.4 0.5 <0.1 1.6 0.0 0.7
Note. Data compiled from Source and accuracy statement for the National Longitudinal Alcohol Epidemiologic Survey. Rockville, MD: Na
tional Institute on Alcohol Abuse and Alcoholism.

except for illicitly used prescription drugs, especial- but among persons aged 18-29, the prevalence of
ly tranquilizers and amphetamines, whose lifetime use was higher for nonblacks than blacks (11.2% vs.
use was more common among older than younger 7.3%). These patterns varied somewhat for individual
blacks. drugs. For example, the age differential was particu-
The prevalence of past-year use of any type of larly strong for hallucinogens, there was no gender
drug was 4.9%: 3.9% for cannabis; 1.5% for illicit use differential in the illicit use of prescription drugs,
of prescription drugs, with opioids the most com- and blacks aged 30 and older were more likely than
monly used (0.6%) of these; 0.6% for cocaine or nonblacks in that age range to have used cocaine or
crack; and 0.3% for hallucinogens (table 1.5). As crack in the past year.
with lifetime use, past-year drug use for all types of The gender, ethnic, and age differentials that
drugs combined was more common among men were obtained from the NLAES data presented in
than women (6.4% vs. 3.6%) and far more prevalent tables 1.3-1.5 correspond closely to those based on
among individuals aged 18-29 (10.7%) than among the National Household Survey on Drug Abuse
those aged 30 and older (3.0%). For all ages com- (NHSDA), despite differences in the age groups
bined, there was no significant difference by race, surveyed and the definitions of substance use. The
18 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

NHSDA sample included individuals age 12 and the Future Survey collect information on the use of
over and classified respondents as drug users on the alcohol and various types of drugs, the descriptive
basis of a single incident of use. Prevalence estimates publications based on these surveys do not indicate
based on the NHSDA are accordingly higher (e.g., the prevalence of multiple drug use, that is, the use
37.2% lifetime use and 11.8% past-year use in in- of more than one type of psychoactive substance
dividuals aged 12 and over in 1993) (Substance within a given time frame. Data from the 1992
Abuse and Mental Health Services Administration NLAES revealed that one third (33.1%) of all U.S.
[SAMHSA], 1995a). adults had never used either alcohol or drugs at any
Data on adolescent substance use are also col- point during their lives. More than half (51.3%) re-
lected annually in the Monitoring the Future Study, ported lifetime use of alcohol but not drugs. The pro-
whose findings indicated that in 1995 the lifetime portions using alcohol and either a single type of
prevalence of any drug use was 28.5% for 8th-grad- drug or multiple drugs were 8.3% and 6.3%, respec-
ersr 40.9% for 1 Oth-graders, and 48.4% for 12th-grad- tively. Lifetime use of a single drug or multiple drugs
ers. The corresponding rates of past-year use were without alcohol use was rare, reported by 0.7% and
21.4%, 33.3%, and 39.0%, respectively. Among 12th- 0.2% of adults, respectively. Patterns of past-year use
graders, rates of lifetime drug use were highest for were similar, except that the proportion using neither
cannabis (41.7%), followed by inhalants (17.8%), alcohol nor drugs was higher (54.8%) and the pro-
stimulants (15.3%), hallucinogens (12.7%), barbitu- portion using alcohol only was lower (40.3%) than
rates (7.4%), tranquilizers (7.1%), and cocaine (6.0%). for the corresponding lifetime estimates.
The prevalence of lifetime alcohol use among 12th- In addition to these national population estimates,
graders was 80.7% (Johnston, O'Malley, & Bachman, studies of emergency room and clinical samples have
1996). revealed widespread multiple drug use. Of more
Data from the NHSDA (SAMHSA, 1995a) indi- than half a million drug-related emergency room ep-
cated that among individuals 12-17 and 18-25 years isodes reported to the Drug Abuse Warning Network
of age, the lifetime prevalence of alcohol use rose (DAWN) in 1994, nearly one third involved the use
throughout the late 1970s and declined between 1979 of alcohol in combination with drugs (SAMHSA,
and 1992, with a very slight upturn between 1992 1996). The annual National Drug and Alcoholism
and 1993. The same trend was observed for cannabis Treatment Unit Survey (NDATUS), which collects
use, whereas the lifetime prevalence of cocaine use data from all providers of alcohol and/or drug treat-
peaked in 1982 and declined between 1982 and ment services, revealed that 40% of all clients in
1993. The patterns for past-year use of alcohol and treatment in 1993 abused both alcohol and drugs,
drugs followed the same pattern. Among individuals 35% abusing alcohol only and 25% abusing drugs
26 years of age and older, the lifetime prevalence only (SAMHSA, 1995b). In a sample of 212 subjects
of alcohol consumption rose during the late 1970s, who provided full screening information for admis-
decreased between 1979 and 1982, and remained sion into an alcohol treatment program, the propor-
fairly stable between 1982 and 1993. Lifetime use of tions of men and women who reported concurrent
cannabis and cocaine increased steadily between use of other drugs were 44% and 41%, respectively,
1986 and 1993 within this age group, although the for cannabis, 32% and 33% for amphetamines, 22%
increases in cannabis use after 1988 were slight. Data each for sedatives, 17% and 10% for opiates, and 17%
from the Monitoring the Future Study indicated that and 13% for hallucinogens (Schmitz et al., 1993). In
the prevalence of past-year cannabis use among 8th-, another study of an inpatient treatment sample, 63%
10th-, and 12th-graders increased sharply between of the subjects reported concurrent use of alcohol
1991 and 1995, reversing a long-term trend toward and any other type of drug, and almost all of these
decreasing use that began in the early 1980s. These concurrent users reported at least one episode of si-
data also showed an increase during the 1990s in the multaneous use (i.e., use on the same day) of alcohol
prevalence of past-year use of other drugs (e.g., inhal- and other drugs (Martin et al., 1996a). In a mixed
ants and hallucinogens), but the statistical signifi- treatment/community sample of adolescents, the
cance of these increases cannot be assessed from the mean number of illicit drugs ever used was highest
published data (Johnston et al., 1996). (3.8) for adolescents meeting the DSM-/V criteria for
Although both the NHSDA and the Monitoring alcohol dependence, next highest (3.1) for those
 CLASSIFICATION, PREVALENCE, AND COMORBIDITY 19

meeting the criteria for alcohol abuse, and lowest epidemiological studies in the early 1980s. The sec-
(1.9) for those without either diagnosis (Martin, Kac- ond was the National Comorbidity Survey (NCS), a
zynski, Maisto, & Tarter, 1996b). national probability sample of 8,098 respondents
Data on multiple drug use have provided the aged 15-54, conducted in 1991 (Kessler, McGona-
foundation for research on the developmental stag- gle, & Shanyang, 1994). The most recent national
ing of substance use, which indicates a fairly consis- survey on the prevalence of alcohol and drug use
tent sequencing in the initiation of alcohol and other disorders is the National Longitudinal Alcohol Epi-
drug use, and for the gateway theory of substance demiologic Survey (NLAES), in which direct face-
use, which proposes that adolescent alcohol and/or to-face interviews were administered to 42,862 re-
cigarette use leads to (or increases the risk of) canna- spondents, aged 18 and older, residing in the nonin-
bis use and ultimately the use of hard drugs such stitutionalized population of the contiguous United
as cocaine (see, for example, Kandel &Logan, 1984; States (Grant, Peterson, Dawson, & Chou, 1994).
Kandel & Yamaguchi, 1993; Welte & Barnes, 1985). Although these three major national surveys all
Multiple drug use also has important implications for measured alcohol and drug use disorders, they are
treatment. Studies of treatment samples generally not comparable. Considerable differences between
have indicated that multiple drug users are younger, the surveys existed in terms of the diagnostic criteria
more likely to be male, more likely to be single, and represented, the survey instruments used, the amount
more likely to live alone than individuals with alco- and type of psychometric testing of the instruments,
hol problems only (Brown, Seraganian, & Tremblay, and definitions of lifetime diagnoses. The NLAES
1993, 1994; Schuckit & Bogard, 1986). Other studies was the first national survey to measure alcohol and
have shown that multiple drug users have more anti- drug use disorders according to the most recent psy-
social problems, a greater history of depression and chiatric classification, the DSM-IV. Most notably,
suicide attempt, higher levels of impulsivity, lower the NLAES survey instrument required alcohol and
levels of self-control, more severe interpersonal and drug symptoms to cluster together chronologically in
intrapsychic conflicts, and fewer personal coping re- order for a diagnosis of dependence to be made. In
sources than persons with alcohol use problems only the EGA and NCS surveys, dependence on alcohol
(Brown & Fayek, 1993; Schuckit & Bogard, 1986). or any drug was defined as the lifetime accumulation
Not surprisingly, multiple drug users often have a of the required number of dependence symptoms to
poorer treatment outcome than do individuals treat- achieve a diagnosis, even though their occurrence
ed for alcohol problems alone (Brown et al., 1993; may have been spread out over many years. Unlike
Schuckit & Bogard, 1986). Thus, multiple drug users the survey instruments used in the EGA and NCS,
may require forms of treatment that do not rely on the NLAES diagnostic instrument was also subjected
strong personal resources or a social network of sup- to a test-retest study that assessed its reliability in a
port, that do attend to comorbid psychiatric prob- general population sample similar to the samples for
lems, and that additionally deal with the complex is- which it was intended to be used (Grant, Harford,
sues surrounding the reinforcement of craving and Dawson, Chou, & Pickering, 1995).
the inappropriateness of using certain types of drugs The most recent prevalence estimates of lifetime
in treatment under the circumstances of multiple and past-year alcohol use disorders derived from the
drug use. NLAES appear in table 1.6, disaggregated by gender,
ethnicity, and age. The past-year prevalence of com-
bined alcohol abuse and dependence was 7.4%, rep-
PREVALENCE OF ALCOHOL AND resenting 13,760,000 Americans, while the lifetime
DRUG USE DISORDERS rate was much higher (18.2%). More respondents
were diagnosed with dependence during the past
The Epidemiologic Catchment Area (EGA) survey year (4.4%) and on a lifetime basis (13.3%) than
was the first of three national studies to assess alcohol were diagnosed with alcohol abuse for those two
and drug use disorders according to psychiatric diag- time periods (3.0% and 4.9%, respectively).
nostic criteria (Robins, Locke, & Regier, 1990). In Regardless of time frame, prevalence rates for al-
this survey, 18,571 respondents, aged 18 and older, cohol abuse and alcohol dependence were greater
were interviewed in a series of five community-based among men than women and greater among non-
TABLE 1.6 Prevalence (%) of Lifetime and Past-Year DSM-JV Alcohol Abuse and
Dependence by Gender, Ethnicity, and Age

Total alcohol
Alcohol abuse only Alcohol dependence abuse/dependence
Sociodemographic
characteristics Lifetime Past year Lifetime Past year Lifetime Past year

Total 4.9 3.0 13.3 4.4 18.2 7.4

18-24 6.7 6.5 19.9 9.4 26.6 15.9
25-44 6.2 3.0 15.7 4.3 21.9 7.3
45-64 3.7 1.4 9.9 2.1 13.7 3.5
65+ 1.3 0.3 3.4 0.4 4.7 0.7
Total men 7.0 4.7 18.6 6.3 25.5 11.0
18-24 8.6 9.3 25.0 12.8 33.7 22.1
25-44 8.2 4.6 21.2 6.1 29.4 10.7
45-64 6.1 2.4 15.1 3.2 21.2 5.6
65+ 2.5 0.6 6.4 0.6 8.9 1.2
Total women 2.9 1.5 8.4 2.6 11.4 4.1
18-24 4.8 3.8 14.8 6.0 19.5 9.8
25-44 4.2 1.5 10.3 2.5 14.5 3.9
45-64 1.4 0.4 5.2 1.1 6.6 1.5
65+ 0.4 <0.1 1.3 0.2 1.7 0.3
Total nonblack 5.2 3.2 13.9 4.5 19.1 7.7
18-24 7.3 7.2 21.7 10.1 29.0 17.3
25-44 6.7 3.2 16.5 4.2 23.2 7.4
45-64 3.9 1.4 9.9 2.0 13.8 3.5
65+ 1.3 0.3 3.5 0.4 4.8 0.7
Nonblack men 7.4 4.9 19.2 6.4 26.6 11.3
18-24 9.3 10.0 26.7 13.5 36.0 23.5
25-44 8.8 4.8 22.2 6.1 30.9 10.9
45-64 6.4 2.5 14.9 3.1 21.3 5.6
65+ 2.6 0.6 6.5 0.6 9.1 1.2
Nonblack women 3.2 1.6 8.9 2.6 12.1 4.3
18-24 5.3 4.3 16.6 6.7 21.9 10.9
25-44 4.6 1.6 10.9 2.4 15.5 3.9
45-64 1.5 0.4 5.2 1.0 6.7 1.5
65+ 0.4 <0.1 1.3 0.3 1.7 0.3
Total black 2.2 1.5 8.6 3.8 10.8 5.3
18-24 2.6 2.5 8.7 5.0 11.3 7.4
25-44 2.5 1.8 9.5 4.5 12.0 6.3
45-64 2.2 0.5 9.9 2.9 12.0 3.4
65+ 0.4 0.0 2.8 0.3 3.2 0.3
Black men 3.5 2.5 13.3 5.8 16.8 8.3
18-24 3.9 4.0 13.6 8.4 17.5 12.3
25-44 3.7 2.8 13.4 6.0 17.1 8.8
45-64 4.0 1.2 16.0 4.0 20.1 5.2
65+ 0.8 0.0 5.8 0.8 6.6 0.8
Black women 1.1 0.7 4.8 2.2 5.9 2.9
18-24 1.5 1.2 4.5 2.1 6.1 3.3
25-44 1.4 1.0 6.3 3.2 7.7 4.2
45-64 0.6 <0.1 4.9 1.9 5.5 1.9
65+ 0.1 0.0 0.8 0.0 1.0 0.0
Note. Data compiled from Source and accuracy statement for the National Longitudinal Alcohol Epidemiologic Survey.
Rockville, MD: National Institute on Alcohol Abuse and Alcoholism.
 CLASSIFICATION, PREVALENCE, AND COMORBIDITY 21

blacks than blacks. Rates for nonblack men and IV drug use disorders by gender, ethnicity, and age
women often exceeded the rates of their black coun- are shown in table 1.6. With the exception of canna-
terparts by over 30%. Prevalence rates of alcohol bis abuse and dependence, rates for past-year abuse
abuse and dependence, measured separately or com- and dependence for most drugs also were generally
bined, also decreased as a function of age, with the less than 1% for each gender, age, and ethnic sub-
highest rates among respondents 18-45 years old rel- group of the population. Similar to trends observed
ative to those 45 years and older, regardless of gender for alcohol use disorders, the rates of abuse and/or
or ethnicity. Possible explanations for the decline in dependence on all drugs taken singly were greater
both past-year and lifetime alcohol abuse and depen- for men than women, greater for nonblacks than
dence rates with age may include faulty recall ac- blacks, and greater among the younger age group
companying increasing age, lower survival rates (<30 years) than to the older age group (30 years and
among alcoholics, and various time-dependent re- older).
sponse styles. Alternatively, the age gradient may re-
flect a true cohort effect, that is, that alcohol abuse
and dependence are more prevalent among the COMORBIDITY BETWEEN
younger generation of Americans. ALCOHOL USE DISORDERS,
Although alcohol abuse and dependence were DRUG USE DISORDERS,
more common among men than among women, AND PSYCHIATRIC DISORDERS
there was evidence of convergence of the rates be-
tween the sexes in the youngest age groups. The Over the last two decades, there has been increasing
men-to-women ratios (i.e., the men's rate divided by interest in the relationship between alcohol and drug
the women's rate) were lowest in the 18- to 29-year- use disorders and various forms of other psychopath-
old age group. However, when the men-to-women ology. During this time, considerable controversy has
ratio was examined separately for each ethnic group, arisen surrounding several issues in comorbidity re-
it was clear that the rate converged among the youn- search. Opinions have varied widely on the reasons
gest age groups only among nonblacks, a finding sug- for comorbidity. There are several possible explana-
gesting that nonblack women may be catching up. tions for comorbidity, including the toxicity hypothe-
This phenomenon does not generalize to black sis, in which alcohol or drug use disorders are viewed
women because the men-to-women ratios in blacks as causing the comorbid disorder, and the self-medi-
were shown to decrease as a function of age. cation hypothesis, in which an individual drinks or
Prevalences of DSM-IV drug use disorders were uses drugs to self-medicate the comorbid disorder
much lower than the corresponding rates of alcohol (i.e., the comorbid disorder causes the alcohol or
use disorders (table 1.7). Rates for past-year abuse drug use disorder). It is also possible that both disor-
and dependence for most drugs were less than 1% in ders are caused by some common factor, or that the
this general population sample, with the exception disorders are etiologically distinct but that each mod-
of cannabis abuse and dependence combined ifies the risk and/or course of the other. In view of
(1.2%). The prevalence of past-year abuse and/or de- the number of comorbid relationships recognized in
pendence on any drug was 1.5%, with the rate of the literature, it is very likely that each of these
dependence (1.1%) exceeding the rate of abuse hypotheses pertains to various subsets of comor-
(0.5%) (data not shown). Overall, the lifetime rate of bidity.
any drug abuse and/or dependence was 6.1%. The Another controversy in the comorbidity field is
rate for lifetime cannabis abuse and dependence whether rules can be developed to reliably differenti-
(4.6%) was greater than the rates for all the other ate organic or substance-induced disorders or syn-
drugs, followed in order of magnitude by abuse and/ dromes that mimic psychiatric disorders but are actu-
or dependence on any prescription drug (2.0%; in- ally the toxic effects of alcohol or drug intoxication
cluding sedatives, tranquilizers, amphetamines, and or withdrawal from independent forms of the psychi-
opioids), cocaine (1.7%), amphetamines (1.5%), sed- atric disorder. A similar issue arises in the differential
atives (0.6%), tranquilizers (0.6%), and hallucino- diagnosis between pure forms of a psychiatric disor-
gens (0.6%) (data not shown). der and those that are induced by a preexisting medi-
The prevalences of lifetime and past-year DSM- cal condition.
 TABLE 1.7 Prevalence (%) of Lifetime and Past-Year DSM-JV Drug Use Disorders by Gender, Ethnicity, and Age

Lifetime Past Year

18-29 18-29
Drag Use Disorder Men Women Black Nonblack years 30+ years Men Women Black Nonblack years 30+ years

Any drug abuse or dependence 8.1 4.2 4.0 6.3 10.2 4.7 2.2 0.9 1.2 1.6 4.0 0.7
Any drug abuse only 4.4 2.0 1.7 3.3 5.2 2.5 1.6 0.5 0.7 1.1 3.0 0.5
Any drug dependence 3.7 2.2 2.2 3.0 5.1 2.2 0.6 0.4 0.6 0.5 1.2 0.2
Prescription drug abuse or dependence 2.5 1.6 0.6 2.2 2.8 1.8 0.3 0.3 0.3 0.3 0.7 0.2
Prescription drug abuse only 1.3 0.7 0.2 1.1 1.3 0.9 0.3 0.2 <0.1 0.2 0.5 0.1
Prescription drug dependence 1.2 0.9 0.4 1.1 1.5 0.9 0.1 0.1 <0.1 0.1 0.2 0.1
Sedative abuse or dependence 0.8 0.4 0.3 0.7 0.7 0.6 0.0 <0.1 0.0 <0.1 <0.1 <0.1
Sedative abuse only 0.4 0.2 0.2 0.3 0.3 0.3 0.0 0.0 0.0 0.0 0.0 0.0
Sedative dependence 0.4 0.2 0.1 0.4 0.4 0.3 <0.1 <0.1 0.0 <0.1 <0.1 <0.1
Tranquilizer abuse or dependence 0.8 0.4 0.4 0.6 0.9 0.6 <0.1 0.1 <0.1 0.1 0.1 <0.1
Tranquilizer abuse only 0.4 0.2 0.2 0.3 0.5 0.3 <0.1 <0.1 0.0 0.1 0.1 <0.1
Tranquilizer dependence 0.4 0.2 0.2 0.3 0.4 0.3 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1
Amphetamine abuse or dependence 2.0 1.0 0.4 1.6 2.1 1.3 0.2 0.1 0.0 0.1 0.4 <0.1
Amphetamine abuse only 1.0 0.3 0.2 0.8 1.0 0.7 0.1 0.1 0.0 0.1 0.3 <0.1
Amphetamine dependence 1.0 0.6 0.2 0.8 1.1 0.6 0.1 <0.1 0.0 0.1 0.1 <0.1
Cannabis abuse or dependence 6.6 2.9 2.9 4.9 8.2 3.5 1.9 0.5 0.8 1.3 3.4 0.5
Cannabis abuse only 4.1 1.7 1.6 3.0 4.9 2.2 1.5 0.4 0.6 1.0 2.6 0.4
Cannabis dependence 2.5 1.2 1.3 1.9 3.3 1.3 0.4 0.1 0.2 0.3 0.8 <0.1
Cocaine abuse or dependence 2.2 1.1 1.6 1.7 2.7 1.3 0.3 0.1 0.5 0.2 0.4 0.1
Cocaine abuse only 0.9 0.4 0.4 0.7 1.0 0.5 0.2 <0.1 0.1 0.1 0.2 <0.1
Cocaine dependence 1.3 0.7 1.2 1.0 1.7 0.8 0.1 0.1 0.4 0.1 0.2 0.1
Hallucinogen abuse or dependence 1.0 0.3 0.1 0.6 1.1 0.4 0.1 <0.1 <0.1 0.1 0.3 0.0
Hallucinogen abuse only 0.5 0.2 <0.1 0.3 0.6 0.2 0.1 <0.1 0.0 <0.1 0.2 0.0
Hallucinogen dependence 0.5 0.1 <0.1 0.3 0.5 0.1 <0.1 <0.1 <0.1 <0.1 0.1 0.0

Note. Data compiled from Source and accuracy statement for the National Longitudinal Alcohol Epidemiologic Survey. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism.
 CLASSIFICATION, PREVALENCE, AND CO-MORBIDITY 23

Disentangling independent from substance-in- flects a positive association between two comorbid
duced disorders can be difficult, because this deter- disorders. An odds ratio of 1.0 or indistinguishable
mination rests largely on a self-report clinical history from 1.0 is considered nonsignificant.
that may be unreliable, particularly when chronic, Despite major differences in interview schedules,
long-standing disorders may be involved. In view of diagnostic criteria, and algorithms, the relative mag-
this issue, it is not surprising that much of the think- nitudes of the rates are quite consistent across the
ing about comorbidity has been focused on the pri- EGA, NCS, and NLAES and between past-year and
mary-secondary distinction, or on which disorder ap- lifetime odds ratios, with the majority of associations
peared first chronologically. The assumption has being smaller for lifetime than past-year time frames.
been that a psychiatric disorder that is primary to an These results suggest that while self-medication of
alcohol or drug use disorder is more likely to be an depression with alcohol may be effective in the short
independent disease entity which will persist in absti- term, it may lead to increased dysphoria and exacer-
nence and require appropriate treatment. Converse- bation of depressive symptoms in the long term. If
ly, a chronologically secondary psychiatric disorder is self-medication were successful in the long term, we
thought to be more likely to result from the toxic would have expected the associations to be lower for
effects of alcohol and drugs and to remit with absti- past-year diagnoses relative to lifetime diagnoses.
nence. The level of association among alcohol and drug
Most of the research on comorbidity has been use disorders was greatest in the two most recent sur-
conducted in treated samples. Data from these clini- veys, the NCS and NLAES (OR > 20), but much
cal studies show wide variation in comorbidity rates lower in the older (EGA) survey. The magnitude of
between alcohol and drug use disorders and other this association and its consistency in the latest two
psychiatric disorders. The observed variation in the surveys, despite their methodological differences,
rates is very likely due to differences in the diagnostic strongly suggest that alcohol and drug use disorders
interviews and criteria used to arrive at diagnoses and are more likely to co-occur today than they were a
differences in the demographic composition of the decade ago on both a lifetime and a concurrent ba-
samples. Regardless of the reported variability, stud- sis. Alcohol and drug use disorders were also more
ies of medical, psychiatric, and substance-abusing pa- highly related to major depression and antisocial per-
tients are not well suited to the study of comorbidity. sonality disorder than to manic disorder or any of
Individuals in treatment are more likely to have mul- the anxiety disorders. This result is consistent with
tiple disorders than cases in the general population, evidence from the clinical literature, in which alco-
thereby spuriously inflating comorbidity rates and hol and drug use disorders, major depression, and
creating an environment ripe for what is referred to antisocial personality disorders sometimes aggregate
as Berkson's bias (Berkson, 1946). in the same family and in the same individuals, indi-
Because of these problems, it is necessary to turn cating that the three disorders may simply be alterna-
to general population samples for more accurate and tive manifestations of the same disorder (Winokur &
precise estimates of comorbidity. However, general Coryell, 1991; Winokur, Rimmer, & Reich, 1971).
population surveys designed to reliably study comor- However, from the limited number of data available
bidity are rare. As previously mentioned, only three from adoption and genetic marker studies, there is
major studies in the United States have considered no consistent evidence of genetic overlap among the
psychiatric comorbidity, including alcohol and drug disorders in this putative spectrum (Cloninger,
use disorders and other psychopathology. These stud- Reich, & Wetzel, 1979; Goodwin et al., 1974; Good-
ies were the EGA conducted in the early 1980s, the win, Schulsinger, Hermansen, Guze, & Winokur,
NCS conducted in 1991, and the NLAES conducted 1973). Further research will be required to deter-
in 1992. mine if these three disorders are heterogeneous clini-
The relationships between current and lifetime cally and etiologically or, alternatively, represent dif-
alcohol and drug use disorders and other psychiatric ferent expressions of the same underlying pathogenic
disorders from these three surveys are summarized in mechanism.
table 1.8. In this table, we present odds ratios as mea- Despite the findings from clinical studies that co-
sures of the strength of an association between disor- morbidity rates vary by gender and age, these specifi-
ders. An odds ratio significantly greater than 1.0 re- cations have been largely ignored in previous general
24 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

TABLE 1.8 Comorbidity Between Current and Lifetime Alcohol and Drug Use Disorders and
Other Major Psychiatric Disorders in the NLAES, NCS, and EGA: Odds Ratios

Current* Lifetime

Alcohol Alcohol
use Drug use use Drug use
Disorder Survey disorder disorder disorder disorder

Drug use disorder NLAES 25.1 _ 13.0 _

NCS 20.6 — 13.7 —
ECA 7.8 — 5.8 —
Major depression NLAES 3.7 7.2 3.6 5.2
NCS 2.6 3.0 1.9 2.4
ECA 2.7 3.4 1.9 3.5
Mania NCS 5.6 5.7 4.9 7.4
ECA 3.8 3.2 4.6
Obsessive-compulsive disorder ECA 3.4 3.4 2.1 3.3
Phobia NCS 2.3 3.9 1.7 2.2
ECA 1.7 1.7 1.4 1.8
Panic disorder NCS 1.4 3.9 1.6 3.0
ECA 4.6 1.0 2.6 3.1
Generalized anxiety disorder NCS 2.7 5.0 2.0 2.9
Posttraumatic stress disorder NCS 2.2 2.9 1.7 3.2
Antisocial personality disorder NCS 11.3 11.5
"EGA — — 14.6 8.9
"Current: ECA and NCS, 6 months; NLAES, 12 months.

population studies. In the NLAES, associations be- the use, giving up important activities to use) and
tween lifetime alcohol and drug use disorders and tolerance and withdrawal symptomatology were rele-
major depression were presented for abuse and de- gated to the dependence category. Unlike the indica-
pendence separately by gender and age (Grant, 1995; tors of DSM-IV dependence, the DSM-IV abuse cri-
Grant & Harford 1995) (see table 1.9). For alcohol teria may reflect societal reactions to substance use
and each drug, the dependence-depression associa- behavior. Women's drinking and drug-taking behav-
tion was greater than the corresponding abuse-de- ior may be more heavily sanctioned than that of men
pression association, and the odds ratios were greater (Makela, 1987; Park, 1983), thereby increasing their
for drug than for alcohol use disorders. vulnerability to societal reaction as reflected in the
Associations between alcohol and drug use disor- DSM-IV formulation of abuse. The increased risk of
ders for all drugs combined and between depen- major depression among women diagnosed as abus-
dence and major depression did not differ by gender. ers therefore may reflect the development of major
With the exception of cocaine and hallucinogens, depression as the result of a more adverse societal
the risk for alcohol and other drug abuse and major reaction to their drinking and drug use than that ex-
depression was consistently greater for women than perienced by men. The finding that women also do
men. One reason for this observed risk differential not demonstrate greater abuse-depression associa-
relates directly to the definition of abuse underlying tions than men for cocaine and hallucinogens impli-
the comorbidity rates. The DSM-IV defines alcohol cates the importance of the context in which drug
and drug abuse, separately from dependence, as so- taking occurs. Cocaine and hallucinogen use fre-
cial, occupational, legal, and interpersonal conse- quently takes place among subcultures of society
quences arising from substance use. Indicators of pat- within which women may be protected from societal
terns of compulsive use (e.g., impaired control over reactions through peer support and approval.
 CLASSIFICATION, PREVALENCE, AND COMORBIDITY 25

TABLE 1.9 Lifetime Comorbidity Between DSM-IV Alcohol and Drug Use Disorders and
DSM-IV Major Depression by Gender and Age: Odds Ratios

J8-29
Alcohol/drug use disorder Men Women years 30+ years Total

Alcohol abuse or dependence 4.2 4.0 2.8 3.8 3.6

Alcohol abuse only 1.5 2.1 1.4 1.7 1.7
Alcohol dependence 4.3 4.3 2.9 4.1 3.8
Any drug abuse or dependence 5.5 5.9 4.3 5.3 5.2
Any drug abuse only 3.2 4.0 2.6 3.4 3.3
Any drug dependence 7.2 7.3 5.5 7.1 6.9
Prescription drug abuse or dependence 6.5 6.7 5.3 6.6 6.3
Prescription drug abuse only 3.9 5.1 3.6 4.3 4.1
Prescription drug dependence 9.7 8.0 7.1 9.1 8.6
Sedative abuse or dependence 6.7 6.1 5.2 6.5 6.1
Sedative abuse only 3.8 4.9 3.4 4.2 3.9
Sedative dependence 10.1 7.3 7.3 9.1 8.5
Tranquilizer abuse or dependence 6.6 7.1 5.3 6.9 6.5
Tranquilizer abuse only 4.2 6.6 4.1 4.9 4.8
Tranquilizer dependence 9.6 7.4 7.5 8.8 8.3
Amphetamine abuse or dependence 6.4 6.6 4.4 7.1 6.2
Amphetamine abuse only 3.7 5.2 2.9 4.6 4.0
Amphetamine dependence 10.3 8.0 6.0 10.5 8.9
Cannabis abuse or dependence 4.8 5.8 3.8 4.7 4.7
Cannabis abuse only 3.0 4.2 2.5 3.2 3.1
Cannabis dependence 7.3 8.0 5.4 7.4 7.0
Cocaine abuse or dependence 5.3 5.2 3.6 5.5 5.0
Cocaine abuse only 5.1 4.3 2.6 5.9 4.5
Cocaine dependence 5.1 5.7 4.2 5.1 5.1
Hallucinogen abuse or dependence 7.4 5.4 4.4 7.1 6.3
Hallucinogen abuse only 6.9 4.5 4.6 5.7 5.7
Hallucinogen dependence 7.6 7.2 4.1 8.6 6.8
Note. Data compiled from Source and accuracy statement for the National Longitudinal Alcohol Epidemiologic Sur
vey. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism.

The association between alcohol and drug use use is frequently accompanied by dysphoria (Ellin-
disorders and major depression was consistently great- wood, 1979; Post, Kotlin, & Goodwin, 1974). Alter-
er in the older age group than in the younger age natively, these findings may merely reflect age differ-
group. This result is consistent with evidence from ences in the lifetime risk of both drug use disorders
clinical studies that suggest that a variety of drugs are and major depression. Although major depression
often used to self-medicate depression. Specifically, was strongly related to both cannabis and hallucino-
the mood effects of central nervous system depres- gen abuse and dependence, these two drug classes
sants, such as alcohol, tranquilizers, and sedatives, are not usually associated with the self-medication
have been shown to be variable, initially causing eu- paradigm as it relates to major depression. However,
phoria, but then producing dysphoria, particularly chronic high-dose use of cannabis and hallucinogens
with prolonged use among chronic users. The find- may be accompanied by the development of amo-
ing that risk of comorbidity increases with age ap- tivational syndrome, characterized by anhedonia,
pears to confirm that self-medication for depression chronic apathy, difficulty concentrating, and social
with alcohol, tranquilizers, and sedatives may be ef- withdrawal (Cohen, 1981), symptoms strikingly simi-
fective in the short term but that chronic high-dose lar to those of major depression. Alternatively, failure
26 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

to extract clear relations between specific drugs of gitudinal data would help elucidate the causes and
choice predicted by the self-medication hypothesis as the natural history of alcohol and drug use disorders
ameliorating major depression may be the result of and would provide the basis for understanding the
the common phenomena of polydrug abuse and de- pathophysiological processes underlying them. Since
pendence. adolescence is a high-risk period for the development
of alcohol and drug use disorders, the longitudinal
study of the chronology of alcohol and drug use dis-
FUTURE DIRECTIONS AND TRENDS: orders and other forms of psychopathology should
CLASSIFICATION, PREVALENCE, prove to be most informative. Longitudinal research
AND COMORBIDITY also has the potential to define important subtypes of
alcohol and drug use disorders defined by comorbid-
The future evolution of the classification of alcohol ity and to identify accompanying risk factors helpful
and drug use disorders is likely to entail a continua- in prevention, treatment, and rehabilitation.
tion of the trend toward differentiating dependence
disorders from other substance-related disabilities as
Key References
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ing factors. It is also expected that future changes in drug use disorders and major depression: Results of
classification systems will depend more and more on a national survey of adults. Journal of Substance
empirical data for their justification, a trend begun Abuse, 7, 481-497.
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Recent efforts by behaviorally oriented scientists should P., Dufour, M., & Pickering, R. (1994). Prevalence
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 2

The Course of Treated and

Untreated Substance Use Disorders:
Remission and Resolution,
Relapse and Mortality
John W. Finney
Rudolf H. Moos
Christine Timko

Each person's life has its unique course, and that Rounsaville & Kleber, 1985; Sobell, Cunningham, &
course can be understood in terms of multiple di- Sobell, 1996; Tucker & Gladsjo, 1993). Cohen and
mensions and behaviors. In this chapter, we focus on Cohen (1984) coined the term clinician's illusion to
the course of substance abuse/dependence (disorders refer to the selective, pessimistic perceptions of prac-
involving alcohol, nicotine, and other drugs—parti- titioners regarding the course of the disorders they
cularly, heroin) and describe the more common life treat.
trajectories and influences that alter the course of In contrast, some analysts have provided very opti-
these disorders. mistic views on the long-term outcome of psychoac-
Practitioners offering substance abuse services of- tive substance addiction. For example, based on a
ten see patients return for treatment repeatedly over records search, Winick (1962) argued that, over time,
a period of years. As a result, they are likely to con- about two thirds of persons treated for heroin addic-
clude that substance use disorders are chronic, pro- tion "mature out" of their dependence, typically in
gressive conditions. However, those beliefs are based their 30s. Similarly, Drew (1968) suggested that alco-
on observations of a restricted subset of individuals: holism is a "self-limiting" disease.
those with the most severe, chronic forms of sub- The research reviewed ' i this chapter, though not
stance use disorders. In this regard, substantial empir- without limitations, provides a more comprehensive
ical evidence indicates that persons who seek treat- and balanced perspective on the course of substance
ment for substance abuse are more impaired than use disorders. We address the following questions:
persons not seeking treatment (Finney & Moos, What is the course and long-term outcome of treated
1995; Fiore et al., 1990; Graeven & Graeven, 1983; and untreated substance use disorders? To what ex-

30
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 31

tent do persons with substance abuse/dependence ex-

Long-Term Functioning in
hibit progression in the severity of their symptoms?
Community Samples
Can persons who are stably remitted function as well
as individuals who never have had substance use dis- We located only two long-term follow-up studies that
orders? focused on alcohol use disorders in community sam-
After reviewing research on the course and long- ples. In one, Ojesjo (1981) reported outcomes for 96
term outcomes of substance use disorders, we focus alcoholic men who had been interviewed initially 15
on one end point for some addicted persons: prema- years earlier. The men, whose age at baseline aver-
ture death. We examine the link between active ad- aged 47 years, were categorized at that point as
diction and heightened mortality risk. Then, we fo- "abusers" (heavy drinkers with "medical and social
cus on course changes and the role of personal and disabilities"); "addicts," with generalized dependence
environmental factors in remission, resolution, lapse, symptoms; or "chronics," who had dependence
and relapse. Because of the intended practitioner au- symptoms and medical comorbidities. None received
dience, we focus more attention on findings for intensive treatment during the course of the study.
treated samples, and in the concluding section, we At the 15-year follow-up, 26% had died. Among the
consider implications for treatment. As will become survivors, 41% (2.7% per follow-up year) were in re-
apparent, there is a larger body of research on these mission. The surviving "abusers" had the best out-
issues with respect to alcohol use disorders than for comes, with 64% in remission, followed by "addicts"
smoking and other drug abuse. (18% in remission), and "chronics" (none in remis-
sion).
Vaillant (1995, 1996) presented long-term follow-
THE COURSE OF SUBSTANCE up data on two quite different community samples,
USE DISORDERS whose members had met DSM-III criteria for alco-
hol abuse (some also met criteria for dependence) at
It is inaccurate to speak of the course of any addic- some point in their lives. One group was made up of
tion, as the course for any individual is affected by 150 inner-city men (the "Core City" sample) who
numerous personal and environmental factors, in- had initially been control group members in a study
cluding any other addictions. Thus, in referring to of juvenile delinquency. The "College" sample con-
the course of a substance use disorder, one is refer- sisted of 55 men originally assessed as sophomores at
ring less to its "natural history" as it unfolds in some Harvard University for a study of "normal develop-
inexorable way (Edwards, 1984), than to the "ca- ment."
reers" of the disorder (Edwards, 1984) as they are Long-term follow-up data were secured on 112
shaped by varying personal and environmental fac- men in the Core City sample and 44 men in the
tors for different individuals. In this section, we focus College sample. By age 60, 28% of the men in the
on long-term outcomes and the typical course for al- Core City sample had died. Among the survivors,
cohol, other drug (primarily heroin), and nicotine 59% were in remission, with about three abstainers
addiction. for each controlled drinker (Vaillant, 1996). The
men in Vaillant's College sample exhibited a differ-
ent pattern of outcome when they were 60 years old.
Course of Alcohol Use Disorders
A smaller percentage had died (18%), and among the
Two types of findings from longitudinal studies pro- survivors, only 27% were in remission and about
vide evidence on the course of alcohol use disorders: equally divided between abstainers and controlled
data on individuals' functioning at a long-term fol- drinkers. By age 70, 40% of the College sample men
low-up point and a smaller body of results on the had died. Remission was slightly less prevalent (47%)
course of alcohol use disorders for groups of individ- among the survivors than continuing alcohol abuse
uals who have been studied repeatedly over time. We (53%) (the Core City sample has been followed only
examine separately the data for community (essen- to age 60 at this point).
tially untreated) and clinical samples that have been Overall, these two studies of community samples
tracked for 8 years or more. suggest that around 3% of individuals with alcohol
32 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

use disorders experience remission each year. How- thereafter. Age 40 also marks the point at which
ever, annual remission rates are difficult to calculate some men in the sample began dying; among those
for Vaillant's (1995, 1996) samples, where, unlike in who died, more were active alcohol abusers than ab-
Ojesjo's (1981) study, the follow-ups for some men stainers before their deaths. On a more optimistic
began before their alcohol use disorders had devel- note, many of the surviving men resolved their alco-
oped. hol abuse, as noted earlier, by either becoming ab-
stainers (the more prevalent form of resolution) or
controlled drinkers.
Course of Alcohol Use Disorders in
The onset of alcohol abuse occurred at a later age
Community Samples
for many College sample men than for the members
A more complete picture of the typical course of of the Core City sample, and a smaller percentage
alcohol use disorders requires data on individuals' (38%) of the College men ever met criteria for alco-
functioning at intervening points, in addition to func- hol dependence (all met criteria for abuse at some
tioning at a long-term follow-up. Using retrospective point). The prevalence of alcohol abuse/dependence
accounts from 286 essentially untreated persons (170 peaked at a later age (50) as well and continued later
men and 116 women), Schuckit, Anthenelli, Buc- in the lives of many of the College sample men.
holz, Hesselbrock, and Tipp (1995) outlined the Overall, Vaillant (1995) observed that "the reason
course of alcoholism in terms of the typical age at that alcoholism is relatively uncommon after the age
which 44 life events occurred. Study participants re- of 60 is that roughly 2 percent of alcohol-dependent
ported drinking more than intended at an average individuals become stably abstinent every year and
age of 21 and developing tolerance at 23 years of age. after age 40 roughly 2 percent die every year" (p.
Objections from family, friends, or physicians ensued 152).
at age 24, on average, and respondents first consid- Clearly, various alcohol addiction careers are sub-
ered themselves excessive drinkers at age 26. A first sumed in the data for Vaillant's two samples. Some
period of abstinence of 3 months or more was experi- persons reached criteria for alcohol abuse at an early
enced by 181 of these individuals at age 28, followed age and either became abstinent or engaged in con-
by a second period of 3 months or more at 30 (N = trolled drinking before other persons in the sample
98) and a third period of abstinence at 34 (N= 50). first met criteria for alcohol abuse. We discuss later
Although retrospective data, such as those of factors that may account for various courses and
Schuckit et al. (1995), are valuable, prospective stud- course changes when we focus on factors associated
ies provide a more accurate perspective of the vari- with remission, resolution, lapse, and relapse.
able courses that alcohol abuse/dependence takes in
individuals' lives. Vaillant's (1995, 1996) is the most
Progression of Alcohol Use Disorders
lengthy and in-depth prospective study of the course
of alcoholism. Participants in both of Vaillant's sam- One of the questions that longitudinal studies of
ples completed multiple interviews, so it was possible persons with alcohol use disorders can address is
to determine their status at various stages in their whether such conditions are progressive. Retrospec-
lives. Vaillant's (1995, 1996) analyses reveal a differ- tive studies of alcohol-dependent persons have sug-
ent pattern of functioning over time for his two sam- gested progression. In one of the earliest, Jellinek
ples. The relevant data for the Core City sample are (1952) interviewed members of Alcoholics Anony-
presented in figure 2.1 and those for the College mous (AA), who reported a sequence of the symp-
sample in figure 2.2. toms characterizing the "disease of gamma alcohol-
For many of the Core City men, alcohol abuse ism" that was similar to that described above in the
began relatively early in their lives (over 25% met study by Schuckit et al. (1995).
criteria for alcohol abuse by age 20). Although all of Thus, if one begins with a sample of persons who
the men met criteria for alcohol abuse at some point, meet criteria for abuse/dependence and asks them to
51% also met criteria for alcohol dependence. The reconstruct the sequence of events, the results are
prevalence of alcohol abuse/dependence in the Core likely to reveal progression. However, persons who
City sample was the highest at age 40 and decreased do not exhibit progression would not be included in
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 33

FIGURE 2.1 Quinquennial alcohol use status of the Core City men who met criteria for DSM-III alcohol
abuse. ALC indicates the proportion of deaths that occurred among alcohol abusers; ABS, the proportion
among stably abstinent men. Reprinted by permission from Vaillant (1996), Archives of General Psychiatry,
S3, 243-249. Copyright 1996, American Medical Association.

such studies. Thus, retrospective and prospective in cutting down; and symptoms of withdrawal and
studies of more representative samples that include restriction of activities. Among the individuals who
persons who do and do not meet criteria for a diag- indicated one or more symptoms, 44% of men and
nosis of alcohol dependence provide more accurate 50% of women exhibited symptoms in the first clus-
data on the issue of progression. ter; 31% of men and 28% of women, exhibited symp-
In a retrospective study with a general population toms in the first and second clusters; and 17% of
sample, Nelson, Little, Heath, and Kessler (1996) in- men and 13% of women exhibited symptoms in all
vestigated the lifetime prevalence and age of onset of three clusters. For 83% of the sample with symptoms
each of nine symptom criteria for DSM-III-R alcohol in more than one cluster, transitions from one cluster
dependence (roughly speaking, three criteria must to another, based on recalled age of onset of symp-
have been present for a diagnosis of alcohol depen- toms, reflected the expected progression from abuse
dence). Symptoms were broken down into three to tolerance to withdrawal symptoms. Thus, not all
clusters: symptoms of abuse; symptoms of tolerance, persons with symptoms of alcohol dependence ex-
increasing time spent with alcohol use, and difficulty hibited progression, but if they did, their symptoms
34 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

FIGURE 2.2 Quinquennial alcohol use status of the College men who met criteria for DSM-II1
alcohol abuse. ALC indicates the proportion of deaths that occurred among alcohol abusers; ABS,
the proportion among stably abstinent men. Reprinted by permission from Vaillant (1996), Archives
of General Psychiatry, 53, 243-249. Copyright 1996, American Medical Association.

followed a course similar to that identified in retro- sion. Overall, studies of (predominantly) untreated
spective studies of treated alcohol-dependent per- populations provide little support for the notion of an
sons. inevitable progression of symptoms for persons with
In his prospective study, Vaillant (1995) observed earlier stage alcohol-use disorders. Both a "clini-
that between the ages of 45 and 70, the majority of cian's" and a "clinical researcher's illusion" may
the men in the College sample did not change in have been at work in promulgating the notion of in-
terms of the severity of their alcohol abuse. Specifi- evitable progression.
cally, 20 of 22 men who met criteria for abuse did
not progress to dependence and continued to exhibit
Long-Term Outcome of Treated Alcoholism
abuse until their deaths or the final follow-up. Like-
wise, Hasin, Grant, and Endicott (1990) reported Of particular interest to providers of specialized alco-
that only 30% of 71 men in a general population hol treatment services is what happens to patients in
sample who initially reported only indicators of alco- the long run after a treatment episode, the first of
hol abuse exhibited symptoms of alcohol depen- which occurs for many persons with alcohol use dis-
dence 4 years later. In contrast, 46% were in remis- orders in their early 40s (Schuckit, Smith, Anthen-
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 35

elli, & Irwin, 1993). Table 2.1 summarizes findings ity rates than did Ojesjo's (1981) and Vaillant's
from 12 studies with long-term follow-ups that varied (1995, 1996) community samples. Thus, they may
from 8 to 20 years. Remission is defined as absti- not have included as many persons who were more
nence, nonproblem drinking, or substantially im- prone to relapse. On the other hand, the patients in
proved drinking. Remission rates among successfully the treated samples likely were more impaired ini-
followed survivors ranged from 21% (Westermeyer & tially, as we noted earlier.
Peake, 1983) to 83% (O'Connor & Daly, 1985). Re-
mission rates for survivors in samples followed over
Comparing Alcoholic Patients and
longer periods were generally higher, in part because
Community Controls
of the winnowing out of chronic relapsers through
premature death. Do patients experiencing remission at long-term fol-
Remission rates divided by duration of follow-up low-ups "fully recover"? Do they function in other
yield annual rates that range from 2.1% to 7.6% and life areas as well as similar persons who have not ex-
average 4.8%. This average remission rate is higher perienced alcohol use disorders? What are the costs
than the estimated 3% in studies of community sam- of continuing alcohol abuse? Three long-term fol-
ples, although caution should be exercised in attrib- low-up studies (Finney & Moos, 1991; Kurtines,
uting this difference to the effect of treatment. Broad Ball, & Wood, 1978; Vaillant & Milofsky, 1982) indi-
comparisons between community and treated sam- cate that persons who exhibit long-term remission or
ples do not comprehensively control for population resolution function as well as non-problem-drinking
differences in risk factors associated with outcome, controls, but that continued alcohol abuse is associ-
and the patient samples generally had higher mortal- ated with poorer functioning. However, full recovery

TABLE 2.1 Remission Rates in Long-term Follow-Ups of Treated Alcoholics

Mean age Percentage Percentage Percentage

at first Percentage Length of followed deceased remission Annual
contact married follow-up including of those for remission
Study (years) Time 1 (years) deceased followed survivors rate (%)

Cross et al. (1990) 48 — 10.0 84 32 76 7.6

Edwards et al. (1983)
Taylor et al. (1985) 41 100 11.3 87 20 40 3.5
Finney & Moos (1991) - a
100 10.0 82b 19 57 5.7
Langleetal. (1993) 38 72 10.0 94 22 65 6.5
Mackenzie et al. (1986) 41 29 8.0 94 31 44 5.6
McCabe (1986) 45 100 16.6 88 44 65 3.9
Miller etal. (1992)
Miller & Taylor (1980) 45 76 8.0 71 7 28 3.5
O'Connor & Daly (1985) 48 83C 20.0 70 56 83 4.1
Pendery et al. (1982)
Sobell & Sobell (1973) 40 30 10.0 95 21 47 4.7
Vaillant et al. (1983) 30-50 35d 8.0 94 28 48 6.0
Walker (1987) 41 36 8.0-12.5 80 8e 43 4.2
Westermeyer & Peake (1983) 39 7 10.0 93 22 21 2.1
J
74% were age 40 or older.
Of persons agreeing to a study extension at a six-month follow-up.
'Of those persons later followed.
Living with spouse.
e
Some known-to-be-deceased patients were excluded from the sample prior to a follow-up attempt.
36 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

takes time. De Soto, O'Donnell, and De Soto (1989) stead of all patients entering treatment. Thus, we
found a strong relationship in AA members between conclude that among survivors, about 3% experience
length of abstinence and improvement in psychiatric remission each year, on average. This remission rate
symptoms as assessed by the Brief Symptom Inven- is somewhat lower than the rate of almost 5% found
tory. Symptoms dropped substantially within a year in long-term studies of persons treated for alcohol
or two but continued to decline gradually for 10 use disorders.
years or more, at which point symptom levels were
comparable to those in a general population sample.
The Course of Treated Opiate Dependence
Several of the long-term follow-up studies listed in
Course of Drug Abuse
table 2.2 employed multiple follow-ups and thus pro-
With the exception of a few studies of small, nonrep- vide some insight into addiction careers, particularly
resentative samples of drug abusers in the commu- during the posttreatment period. In a follow-up of
nity (e.g., Murphy, Reinarman, & Waldorf, 1989), male heroin-addicted patients who had been treated
long-term prospective studies of the course of drug at a Public Health Service (PHS) hospital, Vaillant
abuse have focused on treated samples, primarily of (1966) observed that about 90% relapsed in the first
opiate/opioid dependent patients. 2 years. On the other hand, the percentage of men
who exhibited active narcotic addiction declined
from 53% at a 5-year follow-up to 25% at an 18-year
Long-Term Outcome of
follow-up (Vaillant, 1973).
Treated Opiate Dependence
Over the 12 years following an index treatment
We found 10 prospective studies (see table 2.2) of episode, around 75% of the patients tracked by Simp-
patients treated for drug abuse (usually opiate depen- son et al. (1986; Simpson & Sells, 1990) used opioids
dence) that included follow-ups of at least 8 years. daily for one or more periods. However, only 27% of
Criteria for "remission" varied across studies. For ex- these patients were actively addicted for more than 3
ample, some studies focused on complete absti- years at a time. The percentage of daily users in the
nence, whereas others described only abstinence entire sample declined from 47% in Year 1 to 24%
from opioids. The percentage of patients "in remis- in Year 12. Cessation of daily use was not invariably
sion" in table 2.2 refers to "remission" among survi- associated with cessation of criminal behavior, how-
vors as defined by the most stringent criterion avail- ever. About half the patients who were no longer us-
able in the study (e.g., abstinence from all illicit ing opioids daily continued to engage in criminal ac-
drugs). tivity.
As was the case in the long-term studies of treated The entire addiction careers (before and after the
alcohol abuse, early death was the unfortunate out- index treatment episode) for the opioid-addicted pa-
come experienced by substantial percentages of pa- tients studied by Simpson and his colleagues (1986;
tients, with long-term mortality rates varying from Simpson & Sells, 1990) averaged about 10 years,
10% to 54% across studies. For surviving patients, the with a range from 1 to 35 years. During their careers,
percentage "in remission" ranged from 30% to 65% these individuals had an average of six treatment epi-
across the 10 studies. When remission rates are di- sodes and, over time, tended to gravitate toward
vided by the number of years of follow-up, the result- methadone therapy.
ing annual remission rates varied from 1.7% (Hser, How stable are remissions among persons treated
Anglin, & Powers, 1993) to 5.1% (Cottrell, Childs- for narcotics dependence? For 78 patients who were
Clarke, & Ghodse, 1985) and averaged 3.7%. both stably abstinent and employed at a 7-year fol-
The remission rates in several of the studies are low-up by Haastrup and Jepsen (1988), 68% were
likely to have been inflated either because of reliance similarly classified 4 years later and another 17%
on record data rather than personal interviews or, in were in the next best outcome category. Not surpris-
the case of Simpson, Joe, Lehman, and Sells (1986), ingly, less stability in positive outcomes was found
because the 12-year follow-up sample was based on over a longer interval by Hser et al. (1993). Of the
persons successfully followed at 6 years (and more men testing negative for narcotics at a 10- to 12-year
likely to be doing well than those not followed), in- follow-up, 45% were in the same category at a 24-
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 37

TABLE 2.2 Remission Rates in Long-term Follow-Ups of Treated Drug Abuse/Dependence Patients

Mean
age at Percentage Percentage
first Primary deceased remission Annual
contact Type of drug of Length of of those for remission
Study (years) Country treatment abuse follow-up followed survivors rate (%)

Cottrell et al. 25 G.B. DDC Opiates 11.0 20 56 5.1

(1985)
Edwards & 21 G.B. DDC Opiates 10.0 15 50 5.0
Goldie
(1987)
Gordon (1983) 22 G.B. Drug clinic Mixed 10.0 18 41 4.1
Haastrup & 21 Den. City treatment IV opioid 11.0 29 37 3.4
Jepsen service or
(1988) hosp.
Hser et al. 25 USA CCAP Opiate 23.0 31 39 1.7
(1993)
Maddux & 26 USA PHS hosp. Opiate 9.5 13 30 3.2
Desmond
(1980)
O'Donnell 42 USA PHS hosp. Opiate 11.6 54 43 3.7
(1969)
Simpson et al. 22 USA Varied Opioid 12.0 10a 60 5.0
(1986)
Simpson et al.
(1982)
Tobutt et al. 25 G.B. DDC Opiate 22.0 36 65 3.0
(1996)
Stimson et al.
(1978)
Wille (1981)
Vaillant (1973) 25 USA PHS hosp. Opiate 18.0 23 45 2.5

Note. G.B. = Great Britain; Den. = Denmark; DDC = drug dependency clinics; PHS hosp. = Public Health Service hospital; MM = metha-
done maintenance; CCAP = California Civil Addict Program.
''Percentage who died between a 6-year and the 12-year follow-up; not from treatment entry.

year follow-up. Another 17% had died and 8% were not develop until at least early adulthood. Smoking
incarcerated; the remaining individuals who were typically begins in adolescence (Chen & Kandel,
tracked were active narcotics users. 1995) and is persistent. For example, Chassin, Pres-
son, Rose, and Sherman (1996) found that the per-
centage of regular (at least weekly) smokers increased
Course of Smoking
from 20% among llth- and 12th-graders to 27% in
We could find no longitudinal study of the course of young adulthood (age 23, on average) and remained
smoking comparable to those by Vaillant on the stable (26%) into later adulthood (average age of 29).
course of alcohol and drug abuse. However, a picture For adolescent smokers, 59% were smokers as adults
of a typical course, at least into middle adulthood, versus only 10% for adolescent nonsmokers. For
can be pieced together with information from vari- young adult smokers, 72% were adult smokers versus
ous sources. only 7% for young adult nonsmokers. Using data
Although drinking and drug use are frequently in- from various birth cohorts, Pierce and Gilpin (1996)
itiated in the teenage years, addiction typically does projected that an adolescent smoker, born 1975-
38 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

1979, would continue to smoke for 15 years, on aver- (see table 2.2). To the extent that (a) individuals
age, if a male and 20 years if a female. "mature out" of addictions and (b) death claims
Once initiated, nicotine addiction appears to many who do not (see the next section), the rates of
have a higher remission rate than that found in the remission can be expected to be higher among older
community samples of persons with alcohol use dis- than among younger persons.
orders. Among offspring of participants in the Fra- The studies we reviewed provide more good news
mingham Heart study, a high 52% of 397 men and for persons with alcohol use disorders. First, such dis-
49% of 497 women smoked when they were inter- orders are not inevitably progressive, and if persons
viewed initially in 1971-1975 at age 20-29. When do recover, their psychosocial functioning is eventu-
they were recontacted 8 years later, 32% of the men ally comparable to sociodemographically similar per-
smokers and 23% of the women smokers had quit, sons who never had alcohol use disorders. In addi-
4% and 3% annual remission rates, respectively (Hu- tion, as we describe in the next section, the mortality
bert et al., 1987). Presumably, most had quit on their risk for persons who successfully resolve substance
own. We were unable to locate long-term follow-up use disorders is lowered.
studies of treated smokers.
The course of smoking is likely to exhibit stronger
cohort effects than is the case for alcohol and other MORTALITY
drug abuse. Whereas the broad social context (aware-
ness of consequences, sanctions and controls, etc.) in Because the course of addictive disorders ends in
which alcohol and drug abuse occur has been rela- premature death for many individuals, it is worth
tively constant over the past 30 years, there has been considering this end point in greater depth. We focus
an increasing awareness of smoking's adverse health on two issues: first, the extent to which persons with
consequences, a declining number of locations in addictive disorders die prematurely, and second, the
which it is acceptable or legal to smoke, and increas- extent to which persons whose substance use disor-
ing social pressure against smoking. Thus, prior stud- ders are in remission, and whether patients who re-
ies may be less accurate indicators of future trends ceive more treatment have a reduced mortality risk
than is the case for long-term studies of alcohol and relative to those who continue as active substance
drug abuse. abusers or receive less treatment.

Summary Alcohol Use Disorders and Mortality

Vaillant (1995) observed that "if alcoholics can but We first examine mortality in extended follow-ups of
survive, they will often recover" (p. 148). The data community and treated samples of persons with alco-
reviewed here suggest that this somewhat optimistic hol use disorders; we then determine the relationship
conclusion can be extended to persons with other of posttreatment drinking status to mortality risk.
substance use disorders. Among survivors, about 3%
of alcohol abusers in community samples, 5% of
Mortality in Community Samples
treated persons with alcohol disorders, 3% of treated
opiate-dependent persons, and 3-4% of smokers ex- The paucity of long-term follow-ups of community
perience remission each year. samples means that few data are available on pre-
On the surface, the findings indicate that the an- dominantly untreated samples of persons with alco-
nual remission rate for persons treated for alcohol hol use disorders. However, in Ojesjo's (1981) sample
use disorders is about two thirds greater than that for of untreated alcoholics, 26% died over the 15-year
opiate-dependent patients (the single long-term fol- follow-up interval for an annual mortality rate of
low-up of smokers is not a sufficient base on which 1.7%. Among those individuals classified at baseline
to rest conclusions). However, that interpretation as "chronics," 44% had died, 24% of "addicts" had
does not take into account the fact that the persons died, and 20% of "abusers" had died. Thus, presum-
treated for alcohol use disorders in these studies (see ably because it is associated with a higher likelihood
table 2.1) tended to be older than persons treated for of continued severity, severity of alcohol use disorder
heroin dependence and other forms of drug abuse at baseline was a mortality risk factor. How these
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 39

mortality rates compared with general population fig- a problem (Marshall et al., 1994). Time to death was
ures was not reported. significantly shorter for men than for women patients
As noted earlier, 28% of the men in Vaillant's in a study by Lewis et al. (1995a).
(1995, 1996) Core City sample died by age 60, as
did 18% of the men in the University sample, rates
Posttreatment Drinking Status
two and three times as high, respectively, as estimates
and Mortality
for demographically similar genera] population
groups. Men who met criteria for alcohol depen- The relationship of posttreatment drinking status to
dence were more likely to die by age 60 in the Col- mortality risk may be of greater relevance to treat-
lege and Core City samples (62% and 32%, respec- ment providers than is patients' pretreatment func-
tively) than men who met criteria for only alcohol tioning. Because of the infrequency of data from in-
abuse (17% and 18% in the two samples, respec- tervening follow-ups, such information is relatively
tively). Accidents and other violent deaths accounted scarce. However, Smith, Cloninger, and Bradford
for more deaths in the earlier years of follow-up; in (1983) found that treated women who were abstain-
later years, heart disease and cancer accounted for ers at a 3-year follow-up had the lowest mortality rate
more deaths (see also Vaillant, Schnurr, Baron, & (8%) 8-9 years later, followed by sporadic/variable
Gerber, 1991). drinkers (17%), social drinkers (20%), and problem
drinkers (54%). At a 21-year follow-up, these percent-
ages were 31%, 40%, 31%, and 66%, respectively
Mortality in Treated Samples
(Smith, Lewis, Kercher, & Spitznagel, 1994). Like-
We have more extensive data on mortality for per- wise, in a study by Barr, Antes, Ottenbertg, and
sons with treated alcohol use disorders. For 11 of the Rosen (1984) of 410 alcohol patients still alive at a
12 long-term follow-up studies in table 2.1 (we ex- 2-year follow-up, 6% of those classified as "not misus-
cluded Walker, 1987, in which some known-to-be- ing" at that point died in the next 6 years, versus the
deceased persons were excluded from the sample significantly greater 15% of those classified as "misus-
prior to initiating the follow-up), annual mortality rates ing." In studies by Feuerlein, Kufner, and Flohr-
ranged from .9% to 3.9% and averaged 2.8%. In an schutz (1994) and Bullock, Reed, and Grant (1992),
earlier review (Finney & Moos, 1991), we found that the mortality risk for patients who had relapsed was
across seven long-term follow-ups, comparisons with three to five times as high as for those who were ab-
general population data (usually adjusted for age, gen- stainers (cf. Finney & Moos, 1991; Pell & D'Alonzo,
der, and, less often, race) indicated that mortality 1973). Overall, the bulk of the evidence suggests a
rates among alcohol patients were 1.6 to 4.7 times substantial reduction in mortality risk for persons
greater than expected, and that they averaged 3.1 with alcohol use disorders who are able to abstain or
times the mortality rate in the general population. to reduce their alcohol intake following treatment.
More recent studies (Hurt et al., 1996; Lewis et
al. 1995a, 1995b; Marshall, Edwards, & Taylor,
Mortality and Treated Drug
1994) have provided additional data on mortality
Abuse/Dependence
rates and rates for different patient subgroups. Their
results generally have been consistent with those we Some variation exists in reported mortality rates for
reviewed previously: 2.2-2.8% of patients died per treated drug abuse patients, as might be expected,
year, rates that were 2.6-3.6 times higher than ex- given the different countries in which the studies
pected. Functioning prior to treatment was related to were conducted, the different treatment systems
mortality risk. Patients classified as "moderately de- which were in place, and the variation in duration of
pendent" at baseline were 2.9 times as likely to die follow-up. For nine studies in table 2.2 (excluding
as community controls, whereas those who were "se- Simpson et al., 1986, in which only persons who
verely dependent" were 4.4 times as likely to die (this were alive at a 6-year follow-up were "eligible" to die
difference was not statistically significant, however; by a 12-year follow-up), annual mortality rates ranged
Marshall et al., 1994). Estimated years of life lost from 1.3% (Hser et al., 1993; Vaillant, 1973) to 4.7%
were related to more alcohol consumption at intake (O'Donnell, 1969), where the patients were older;
and younger age at which drinking was first seen as the average annual mortality rate was 2.0%.
40 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

Although the 2.0% annual mortality rate among coupled with criminal conviction was associated with
treated drug (primarily opiate) abusers is lower than a heightened mortality risk for drug abuse patients
the 2.8% rate for treated persons with alcohol use over a 10-year follow-up.
disorders, the mortality risk of drug abuse (primarily
opiate-dependent) patients relative to members of
Mortality and Smoking
the general population is much higher than that for
alcohol patients. Specifically, across three studies Although smoking does not cause the social and psy-
(Goldstein & Herrera, 1995; Oppenheimer, Tobutt, chological disruption in its active phase that alcohol
Taylor, & Andrew, 1994; Tunving, 1988), patients and drug abuse do, because of its prevalence it ends
being treated for narcotics addiction were from 4 more lives prematurely than alcohol and other drugs
times (Goldstein & Herrera, 1995—male patients combined. Estimates are that over 400,000 persons
only) to almost 12 times (Oppenheimer et al., 1994) in the United States (McGinnis & Foege, 1993) and
as likely to die as their general population counter- 3 million people worldwide (Peto et al., 1996) die
parts. The apparent inconsistency between the an- each year as a result of smoking. Heavy smoking
nual mortality rates and relative mortality risk for al- shortens an individual's life by 8 years, on average,
cohol- and opiate-dependent patients is explained, at and by 16 years for those who die of causes related
least partially, by the substantially greater age of the to smoking (Peto et al., 1996). Persons who are heavy
alcohol patients relative to the drug abuse patients smokers at age 25 can expect a 25% life reduction
(see tables 2.1 and 2.2). In this regard, the relative compared to nonsmokers (Rogers & Powell, 1991).
mortality risk was found to be higher in younger her- Phillips, Wannamethee, Walker, Thomson, and
oin-addicted patients (under 30) than in older pa- Smith (1996) estimated that only 42% of smokers
tients (Oppenheimer et al., 1994; see also the study alive at age 20 would live to age 73 versus 78% of
by O'Donnell, 1969). nonsmokers.
Opiate addiction appears to be a particularly le- In their 15-year follow-up of British men aged
thal form of drug abuse. Tunving (1988) attempted 40-59 at baseline, Phillips et al. (1996) found that
to track 524 patients receiving care at an inpatient 8% of the nonsmokers had died versus 23% of the
treatment and detoxification unit in Lund, Sweden, continuing smokers. Thus, middle-aged smokers ap-
between 1970 and 1978. The "dominating type of pear to have almost three times the mortality risk of
abuse" was determined for each patient: opiates, am- nonsmokers over a 15-year period.
phetamines, or mixed. Patients were traced via regis- Quitting smoking reduces an individual's mortal-
ters to 1984, at which point 62 had died at an average ity risk. Among former smokers included in a Coro-
age of 27.6 years. Overall, patients were 3.5 times as nary Artery Surgery Study Registry, there was an im-
likely to die as members of the general population. mediate decrease in mortality risk within 1 year of
However, opiate addicts had a greater relative mortal- quitting, but for at least 20 years after quitting, for-
ity risk (5.4 for men and 8.0 for women) than did mer smokers still had a somewhat higher risk of mor-
amphetamine users (2.5 for men; no women died) tality than nonsmokers (Omenn, Anderson, Kron-
or mixed drug users (3.0 for men and 2.0 for women) mal, & Vlietstra, 1990). Similar results emerged in a
(see also Engstrom, Adamsson, Allebeck, & Rydberg, study (Kawachi et al., 1993) of 117,000 registered
1991). nurses in the United States whose age range at base-
Finally, although few long-term follow-up studies line was 20-55. The relative risk of mortality for cur-
have examined the relationships between posttreat- rent smokers was 1.9 times greater than that for non-
ment substance use and mortality, the available evi- smokers, whereas the relative risk for former smokers
dence suggests that posttreatment drug abstinence is was 1.3. Nurses who started smoking before they
associated with a reduced mortality risk. Among ac- were 15 years old had the highest relative mortality
tive drug users at a 10- to 12-year follow-up by Hser risk (3.2). Within 2 years of quitting, former smokers
et al. (1993), 23% had died by a 24-year follow-up, had a 24% reduction in their risk of mortality due to
whereas 17% of persons not testing positive at the cardiovascular causes. However, it took 10-14 years
earlier point had died by the later follow-up. Another of abstinence for the mortality risk of former smokers
study (Gordon, 1983) found that active addiction to approximate that of nonsmokers.
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 41

dropped out of methadone maintenance were almost

Summary
three times more likely to die than were patients ac-
Clearly, substance use disorders place individuals at tively involved in treatment. For alcohol patients,
heightened risk of premature death. The relative le- longer periods of inpatient treatment have also been
thality of alcohol, drug, and nicotine addiction is linked to a lower risk of premature death (Bunn,
somewhat difficult to determine, as mentioned ear- Booth, Loveland Cook, Blow, & Fortney, 1994). Al-
lier, because of age and other differences in the sam- though it is impossible in such studies to completely
ples studied. The data we have presented, as well as disentangle the effects of patient characteristics and
a study by Barr et al. (1984), indicate that alcohol of treatment, these findings should bolster the resolve
patients are more likely to die over a given year than of treatment providers and the motivation of patients
are drug abuse patients. However, alcohol patients to remain in treatment.
tend to seek treatment at a substantially older age
than drug abuse patients (see tables 2.1 and 2.2). The
risk of death relative to that of general population CESSATION, REMISSION,
members is similar for alcoholic patients and RESOLUTION, AND RELAPSE
younger drug abuse patients.
Do drug and alcohol patients of the same age The studies we have reviewed here indicate that sub-
have similar mortality risks? We found only one stantial numbers of persons with alcohol, opiate, and
study that addressed this issue. Among middle-aged nicotine abuse/dependence successfully resolve their
and older patients in VA substance abuse treatment disorders. How are such positive outcomes achieved?
programs, the relative risk of mortality over a 4-year Stall and Biernacki (1986) concluded that the pro-
period was 2.42 for patients with only alcohol depen- cess of behavior change is influenced by multiple
dence diagnoses; patients with a drug dependence or physiological, psychological, and social factors and is
drug psychosis diagnosis were 2.93 times as likely to similar in many respects across different substance
die as demographically similar (age, gender, race) use disorders. The essence of current views on how
members of the general population (Moos, Bren- most addictive behaviors are resolved was captured
nan, & Mertens, 1994). Overall, we conclude that by Tuchfeld and Marcus (1984) in their two-stage
drug abuse (particularly opiate dependence; see model of (1) cessation and (2) maintenance.
Tunving, 1988) is a somewhat more lethal disorder
than alcohol abuse or dependence.
Cessation of Substance Use
In many cases, multiple addictions are inter-
woven as causes of early deaths. For example, Hurt The primary impetus in the cessation process is the
et al. (1996) reported that among deceased persons accumulation of substantial costs of substance use
who had received treatment primarily for alcoholism, and the realization by the affected person that those
51% had a tobacco-related and 34% an alcohol-re- negative experiences flow from his or her substance
lated cause of death. Concool, Smith, and Stimmel use. An individual may become aware of the costs of
(1979) concluded that comorbid alcoholism was substance use gradually, or through the occurrence
present in 60% of the deceased methadone patients of some significant event or crisis (Tuchfeld, 1981),
they studied. such as a life-threatening medical condition or a
On a hopeful note, our review indicates that re- spouse's threatening divorce.
mission is linked to reduced mortality risk. Also of An individual's perception of the rising toll of
relevance to treatment providers is evidence that substance use is influenced heavily by objective
treatment involvement is associated with lower mor- events that he or she has experienced with respect to
tality rates. Patients who receive more methadone health, psychological functioning, social relation-
treatment are less likely to die than those receiving ships, employment, and legal status. In addition,
less treatment (Gearing & Schweitzer, 1974; Gron- perception of the costs of substance use may be influ-
bladh, Ohlund, & Gunne, 1990; Segest, Mygind, & enced by anticipated future consequences. For ex-
Bay, 1990). For example, Caplehorn, Dalton, Cluff, ample, the potential health consequences of smoking
and Petrenas (1994) reported that patients who are a prominent impetus for many persons trying to
42 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

quit, particularly if those risks are weighed in per- men. Instead, 20 of 22 men in the College sample
sonal, rather than general, terms (Rose, Chassin, drifted along in a state of alcohol abuse that while
Presson, & Sherman, 1996). not optimal, apparently was tolerable.
In addition to the mounting costs of substance
use, the addicted person may experience diminish-
Maintenance of Change:
ing psychophysiological benefits (the "rush" or tran-
Remission and Resolution
quillity) from substance use, due to the development
of tolerance. At some point, perhaps after an ex- Although important, the decision to change one's
tended period of ambivalence, the decisional bal- substance use behavior or to quit entirely may be
ance of costs and benefits of substance use shifts to fleeting ("It's easy to quit; I've done it many times").
the negative side and the individual decides to quit In a widely cited analysis, Hunt, Barnett, and Branch
(Sobell, Sobell, Toneatto, & Leo, 1993). In a sense, (1971) charted time to relapse following treatment
then, substance use disorders contain the seeds of from 84 studies of smokers. The percentage of ab-
their own resolution (Mulford, 1977; Orford, 1985). stainers was about 35% at 3 months, 25% at 6
The influential role of perceived negative conse- months, and 20% at 12 months. A study they re-
quences in prompting behavior change among un- viewed of patients treated for alcohol abuse/depen-
aided substance abusers is mirrored by its role in trig- dence and one of heroin addiction patients showed
gering treatment entry. In this regard, Finney and similar relapse curves. Among unaided smokers mak-
Moos (1995) found that the "effects" of hardship fac- ing a quit attempt, rates of failure to maintain behav-
tors, which have been the most consistently identi- ior change have been even higher. One study found
fied precipitants of alcohol treatment entry in a num- that 62% of the individuals had returned to smoking
ber of studies, were mediated by individuals' within 15 days (Ward, Klesges, Zbikowski, Bliss, &
perceived severity of their drinking problem. Similar Garvey, 1997); another reported that only 22% of un-
findings emerged in a study of drug abuse patients aided smokers who quit maintained abstinence for
by Power, Hartnoll, and Chalmers (1992). 14 days and only 8% were abstinent for 6 months
What is perceived as a significant substance use (Hughes et al., 1992).
problem by one person may not be by another. Short-term (e.g., 3-6 months) maintenance of
Among problem drinkers, persons of higher socio- change may be referred to as remission. Longer term
economic status (SES) tend to recognize a drinking change can be labeled recovery or resolution. In
problem sooner than lower SES persons: They hit a Tuchfeld and Marcus's (1984) two-stage model, a va-
higher "bottom" (Humphreys, Moos, & Finney, riety of factors contribute to remission and resolu-
1995). Recognizing a substance use problem earlier, tion. These "maintenance factors" include both in-
before a high level of dependence symptoms has de- trapersonal and interpersonal determinants.
veloped, is associated with a greater likelihood of suc- With respect to cognitive intrapersonal factors, a
cessful resolution (Cohen et al., 1989; Dawson, greater commitment to abstinence (Hall, Havassy, &
1996; Rose et al., 1996). Also, the early realization of Wasserman, 1990, 1991) and a stronger sense of self-
a drinking problem may provide persons with more efficacy (Garvey, Bliss, Hitchcock, Heinold, &
options regarding attainable outcomes (e.g., non- Rosner, 1992; McKay, Maisto, & O'Farrell, 1993;
problem drinking). Rose et al., 1996; Stephens, Wertz, & Roffman,
Some persons may fall into an intermediate level 1993) are associated with a greater likelihood of
of addiction, being sufficiently dependent so that maintaining remission/resolution. Behaviorally, indi-
substance use is not somewhat readily discontinued viduals who possess skills to cope with relapse-induc-
(especially at an earlier age; e.g., Cohen et al., 1989; ing situations (Shiftman et al., 1996) and stressful sit-
Dawson, 1996; Rose et al., 1996), but not so depen- uations in general (Moos et al., 1990) are more likely
dent that the costs of substance use become exceed- to have successful resolutions of their substance use
ingly high. Recall that in Vaillant's (1995, 1996) disorders. Donovan (1996) suggests that individuals
study of the course of alcohol use disorders, fewer tend to cope initially by avoiding high-risk situations
men in the College sample ever met criteria for de- or, if they encounter such situations, by seeking so-
pendence, but also fewer resolved their alcohol use cial support. In later stages of resolution, individuals
disorders in comparison to the Core City sample tend to rely less on behavioral coping approaches
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 43

and more on cognitive coping responses, such as fo- Marlatt and Gordon's (1985) conceptualization of
cusing on the negative consequences of prior sub- the relapse process has been predominant and is de-
stance use and the benefits that have accrued as a scribed in more detail by Quigley and Marlatt (chap-
result of behavior change. ter 20, this volume). In brief, however, a lapse is seen
Abundant research indicates that factors outside as a result of a vulnerable person's confronting a
the individual—the controls and support provided by high-risk situation. Eight types of high-risk intraper-
others in his or her social environment—are also im- sonal or interpersonal situations have been reported
portant in maintaining behavior change (Garvey et by persons with alcohol, opiate, and nicotine depen-
al., 1992; Havassy, Hall, & Wasserman, 1991; Rose dence (Marlatt & Gordon, 1985). The most com-
et al., 1996; Sobell et al., 1993). In this regard, Vail- mon two are negative affect and social pressure to
lant (1988) identified three social conditions that, use substances. Not all persons succumb to relapse-
along with such substitute dependencies as medita- inducing situations, however. Vulnerability is caused
tion or exercise, were associated with long-term absti- by a breakdown in the maintenance factors described
nence among both heroin addicts and persons who earlier. For example, a person may have a reduced
had met criteria for alcohol abuse. The social envi- sense of confidence that he or she can maintain ab-
ronment conditions included (a) some form of com- stinence (lowered sense of self-efficacy) or may fail
pulsory supervision (e.g., parole); (b) new social sup- to apply appropriate coping responses.
ports (e.g., new marriage); and/or (c) membership in A lapse often leads to a full-blown relapse
an inspirational group, such as a self-help or religious (Hughes et al., 1992; Ward et al., 1997), but not al-
group that provided hope, inspiration, and self- ways (Gossop, Green, Phillips, & Bradley, 1989). In
esteem. Vaillant (1988) viewed these factors as im- Marlatt's model, a lapse is more likely to lead to re-
posing structure on addicted persons' lives that coun- lapse if the person experiences the abstinence viola-
teracts the conditioned, unconscious aspects of sub- tion effect (AVE). The AVE consists of cognitive dis-
stance use behavior. sonance, caused by the discrepancy between the
During the maintenance process, the former sub- lapse and a person's self-concept as a former sub-
stance abuser gradually assumes the identity and life- stance user, and by the person's attributing the lapse
style of a nonaddicted person. For a former smoker, to stable, internal causal factors. The magnitude of
this lifestyle change may be nothing more profound the AVE is determined by the person's commitment
than finding something else to do after eating or to abstinence, the effort she or he has expended in
drinking, or drinking a glass of juice after waking up maintaining abstinence prior to the lapse, and the
in the morning instead of having a cigarette. For a perceived benefits of renewed substance use. Overall,
person with chronic alcohol or drug dependence, there is less research support for the critical factors in
however, where sustained use has entailed involve- Marlatt's second stage of the relapse process than there
ment in a "deviant" subculture and perhaps criminal is for the first (Bradley, Phillips, Green, & Gossop,
activity, this latter stage of the maintenance process 1992; Brandon, Tiffany, Obremski, & Baker, 1990).
entails developing an entirely new self-concept and
way of life (Frykholm, 1985; Waldorf, 1983).
Summary

Persons with substance use disorders are both capa-

ble of cessation and resolution and vulnerable to
Relapse: The Failure to Maintain
lapse and relapse. Fortunately, substance use disor-
Remission or Resolution
ders provide the impetus for their own resolution in
Unfortunately, remitted substance abusers are often the form of accumulating negative consequences. In
unable to maintain their behavior change. The re- addition, the risk of lapse/relapse decreases as the du-
lapse process, like the resolution process, has been ration of remission/resolution increases (De Soto et
conceptualized as occurring in two stages. First, al., 1989; Loosen, Dew, & Prange, 1990; Vaillant,
there are factors that either make an individual vul- 1995). Both cessation/resolution and lapse/relapse
nerable to or precipitate a slip or lapse. Second, there are complicated processes in which a number of per-
are "maintenance" factors that determine whether or sonal and environmental factors may play a role.
not a lapse will lead to a full-blown relapse. Multiple change attempts, unaided or aided by other
44 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

helping resources, are often involved in successful Because individuals usually seek treatment at
resolutions (Simpson & Sells, 1990; Timko, Finney, times of crisis, it is a point that has significant poten-
Moos, & Moos, 1995). As we discuss below, treat- tial for change. However, because crises are transi-
ment providers can capitalize on "natural healing tory, it is important that treatment seekers be en-
processes" to enhance the likelihood of successful gaged quickly in the treatment process. Initial
resolutions of substance use disorders. therapeutic efforts should focus on strengthening the
individual's decision and commitment to change.
The findings reviewed in this chapter provide empir-
TREATMENT IMPLICATIONS ical data that can be brought to bear in helping pa-
tients to "take stock" (Sobell et al., 1993), that is, to
Researchers investigating the course of substance use weigh the costs and benefits of continued substance
disorders have typically been unimpressed with the abuse versus abstinence or behavior change. For ex-
role of treatment in the remission/resolution process ample, the findings on the heightened mortality risk
(but see Simpson et al., 1986). Their research indi- of continued abuse, along with the reduced mortality
cates that many persons resolve their substance use risk that flows from abstinence, are concrete evi-
disorders without treatment, and for those receiving dence of the severe consequences of continued
treatment, treatment episodes frequently are followed abuse and the benefits of abstinence. More impor-
by relapses, resolutions often occur at points consid- tant, empirical data indicating that persons can re-
erably after treatment has ended, and many treated solve serious substance use disorders, and that those
persons who are functioning well point to other fac- who do recover function as well as persons who were
tors (e.g., family support) as being critical in the reso- never addicted, can enhance patients' sense of self-
lution process (Dawson, 1996; Saunders & Kershaw, efficacy that recovery is possible and can reinforce
1979; Schachter, 1982; Vaillant, 1996; cf. Simpson their perhaps tenuous beliefs that the effort will be
et al., 1986). Orford (1985) spoke for many research- worthwhile.
ers when he argued that the personal and life context Findings on the course of substance use disorders
factors that impinge on the addicted person, al- also have implications for the role of treatment in the
though "'extraneous' when viewed from the treat- maintenance process. Edwards (1989) observed that
ment perspective, operate more intensively, for far a long-term perspective on substance abuse/depen-
longer, and hence seem likely to be by far the more dence forces one "to place the treatment experience
influential" (p. 268). within the enormously important totality of the ebb
Certainly, there are multiple pathways out of ad- and flow of what happens to that person's life—the
diction, and not all involve treatment. Although an job promotions and the redundancies, the broken
episode of treatment may have a modest impact in marriages and the new lovers, children grown up, the
many cases, it may be a critical factor in particular death of parents, brain damage or growth in personal
instances. Stall and Biernacki (1986) noted that in maturity, accidents and inheritances, boom and
the process of resolution of alcohol, heroin, and nic- slump" (pp. 19-20). From this perspective, it makes
otine addiction, "significant accidents," which might sense that treatment should be directed toward help-
have been "rather commonplace during the remit- ing patients improve their life circumstances and en-
ter's problem use career, served at that moment as a hancing their ability to cope with the situations they
powerful catalyst to irrevocably change and reorient confront in their everyday lives.
the remitter's self-concept and corresponding per- The protracted, fluctuating courses of many per-
spective" (p. 16). At times, treatment can play a simi- sons' substance use disorders, with periods of remis-
lar role. Especially for persons receiving treatment sion and relapse, suggest a temporal extension of
for the first time, having sought treatment is a public treatment—that treatment should be available, as
declaration of an intent to change and may be an needed, over a long period, much as treatment is
important "commitment mechanism" (Tuchfeld & available for diseases, such as diabetes, that are
Marcus, 1984). In addition, entering treatment may chronic (O'Brien & McLellan, 1996). In that regard,
remoralize persons who have failed in multiple at- mutual help groups, such as Alcoholics Anonymous,
tempts to change on their own. Cocaine Anonymous, Narcotics Anonymous, and
 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 45

Nicotine Anonymous, can be a stable and consistent Affairs Mental Health Strategic Health Group and
source of support (Humphreys et al., 1995). Health Services Research and Development Service.
Although progression in the severity of substance
use disorders is not inevitable, it does occur. In addi- Key References
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experience successful resolutions than are more im- from the problematic use of substances: An inductive
paired individuals. These findings imply that inter- model derived from a comparative analysis of the al-
ventions should be available for persons with less se- cohol, opiate, tobacco, and food/obesity literatures.
vere disorders (Sobell & Sobell, 1993). With respect International Journal of the Addictions, 21, 1-23.
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revisited. Cambridge: Harvard University Press.
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 THE COURSE OF TREATED AND UNTREATED SUBSTANCE USE DISORDERS 47

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 3

Theories of Etiology of Alcohol and

Other Drug Use Disorders

Michie N. Hesselbrock
Victor M. Hesselbrock
Elizabeth E. Epstein

Research on the etiology of alcohol and drug use temporary bodies of literature in an attempt to eluci-
disorders is a complex, multidiscipline endeavor, and date the current state of research and knowledge on
the set of results reported in the literature is enor- the etiology and maintenance of alcohol and drug
mous. Etiology can be conceptualized on many use disorders. Of course, this task would better be
levels, by means of several different theoretical ap- accomplished in a multivolume book devoted solely
proaches. For instance, individuals who take a dis- to the topic of etiology, so by design, we hope to
ease model approach to addictions would be most provide a framework here for readers to understand
interested in learning about genetic and biological the basic issues in the study of etiology from several
contributions to the disorders. Researchers who different theoretical viewpoints. First, evidence is
adopt a behavioral approach might look for lawful presented for genetic contributions to alcohol and
systems of antecedent and consequent events that drug abuse/dependence. Mechanisms of heritability
initiate and maintain drinking. Personality or devel- are illustrated through a brief discussion of research
opmental theorists, or those interested in comorbid on antisocial personality as an etiological pathway to
psychopathology, might search for mediating path- substance abuse/dependence. Then, biological mod-
ways, such as certain psychiatric disorders or person- els of the risk for developing alcohol abuse/depen-
ality characteristics, to addictive disorders which are dence are reviewed. Clinical heterogeneity among
seen as end points of these other syndromes. Sociolo- substance abusers is then covered in some detail,
gists might examine factors on a more macro level, since a complication in the study of etiology of ad-
such as peer or societal influences that contribute to dictive disorders is the phenotypic and possibly geno-
development and maintenance of addiction. typic complexity of these disorders.
In this chapter, we summarize several major con- Mediating variables, or risk factors, are then dis-

50
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 51

cussed in a section reviewing the literature on psy- (1990) reported a sevenfold increase in the risk for
chopathology (conduct disorder and antisocial per- developing alcoholism among the first-degree rela-
sonality disorder), personality, and temperament as tives of alcoholics as compared to controls.
related to development of alcohol and drug misuse. The dramatic rate of risk for alcoholism reported
Then, various other models of etiology are presented, by these studies could be due to sampling bias (i.e.,
such as behavioral models, family models, peer influ- most studies reporting an increased risk of familial
ences, and sociocultural approaches. alcoholism have been conducted on men). However,
Note that in this chapter, the term alcoholism pedigree studies of the biological relatives of female
may be used interchangeably with and refers to alco- alcoholic patients have found similar high rates of
hol abuse/dependence, and alcoholic is used in this alcoholism among both male and female relatives
chapter to mean "an individual with alcohol abuse (Cloninger, Christiansen, Reich, & Gottesman, 1978;
or dependence." Hesselbrock et al., 1984). Further, a recent study of
female twins has found that both mothers and fathers
were equally likely to transmit the liability for devel-
GENETIC AND BIOLOGICAL MODELS oping alcoholism to their daughters, particularly in
its more severe forms (Kendler, Heath, Neale, Kes-
sler, & Eaves, 1992).
Genetic Factors and the Vulnerability to
While the reported prevalence of alcoholism
Developing Alcohol and Other Drug
among biological family members varies from one
Abuse/Dependence
study to the other, higher rates of alcoholism are con-
Many psychiatric disorders are familial in nature; sistently found among the family members of alco-
that is, the disorder is also often found among other holic persons than among those of nonalcoholic per-
family members. While this increased prevalence sons. Further, there seems to be a positive association
among family members is suggestive of a possible ge- between the rates of alcoholism and pedigree posi-
netic contribution to the development of a disorder, tion (i.e., the rate drops as the biological distance
it is not conclusive. Other types of evidence are also increases). However, it is difficult to separate biologi-
needed that examine the role of both environmental cal (genetic) factors from possible environmental in-
and genetic factors. There is a substantial literature, fluences in family history studies, since members of
based upon studies of monozygotic and dizygotic nuclear families typically share both genetic and en-
twins, half-siblings, adoptees, and extended-family vironmental factors. Adoption studies enable the sep-
pedigrees, suggesting that the mode of transmission aration of genetic and environmental factors. A series
of addiction problems and disorders from parent to of adoption studies have found a strong link between
child has both a genetic and an environmental com- paternal alcoholism and the son's development of al-
ponent. coholism. Using the Danish adoption registers, these
studies indicate that sons of an alcoholic parent have
a similar risk for alcoholism whether raised by the
Alcohol Abuse/Dependence
alcoholic parent or not. Further, the sons were four
The familial nature of alcoholism has long been rec- times more likely to develop alcoholism than sons
ognized and is well documented. A review of this of nonalcoholics, even when adopted away at birth
literature by Goodwin (1979) found that as many as (Goodwin et al., 1974). These findings have been
25% of fathers and brothers of alcoholic patients are replicated by adoption studies conducted in Sweden
themselves affected with alcoholism, while studies of (Bohman, Sigvardsson, & Cloninger, 1981; Clon-
hospitalized alcoholics indicate that as many as 80% inger, Bohman, & Sigvardsson, 1981), as well as in
may have a close biological relative with a lifetime Iowa (Cadoret, Cain, & Grove, 1980).
history of alcohol-related problems (Hesselbrock & Studies of twins also support the role of genetic
Hesselbrock, 1992). Cotton's (1979) review of 39 factors in the development of alcoholism (see review
family history studies estimated a four- to fivefold in- by Hesselbrock, 1995). The majority of twin studies
crease in the risk of developing alcoholism among report increased concordance rates of alcoholism
the first-degree relatives of alcoholics as compared to among monozygotic twins compared to dizygotic
the general population. More recently, Merikangas twins (Kendler et al., 1992; McGue, Pickens, &
52 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

Svikis, 1992; Pickens et al., 1991). Further, a similar- prevalence of drug dependence among the biological
ity in alcohol consumption among twins raised sep- relatives of inpatients with nonalcohol chemical de-
arately has also been reported (Hayakawa, 1987; pendence.
Kaprio et al., 1987; Pedersen, Friberg, Floderus- The preference for similar types of drugs may oc-
Myrhed, McClearn, & Plomin, 1984). These studies cur among family members of drug abusers. For ex-
provide additional support for the role of genetic fac- ample, monozygotic twins appear to display greater
tors (although unspecified) in the vulnerability to al- similarity than dizygotic twin pairs in their prefer-
coholism. ence for, and response to, certain types of drugs
Pickens et al. (1991) studied same-sex twin pairs (Schuckit, 1987). However, not all researchers agree
of subjects who were treated for alcohol or other on these findings. Mirin, Weiss, Sollogub, and Mi-
drug abuse and found a heterogeneous pattern of in- chael (1984) and Mirin, Weiss, and Michael (1986),
heritance. Approximately half of the twins' biological in a study of first-degree relatives of substance abus-
parent or parents were themselves alcoholic. Herita- ers in a treatment program, found differences in the
bility was much stronger for alcohol dependence prevalence of substance abuse in relation to the gen-
than for alcohol abuse; heritability was also typically der of the relative and the choice of substance.Their
much stronger for men than for women (NIAAA, findings indicate that substance abuse disorders (ex-
1993). Further analysis by McGue et al. (1992) cluding alcohol) were less frequent among both the
found that the rates of alcohol and drug dependence male and female relatives of depressant abusers than
and conduct disorder were much higher among among the relatives of opiate or stimulant abusers.
monozygotic male twin pairs than among dizygotic Further, the prevalence of substance abuse disorders
twins of males who were alcohol-dependent or abus- among the female relatives of stimulant and depres-
ing alcohol. Gender differences were apparent in sant abusers was higher than that among male rela-
that among female twins, similar rates of problem be- tives. The opposite was true of the relatives of opiate
haviors were reported by both female pairs. Further abusers, where more male relatives than female rela-
gender differences were found in terms of age of on- tives were found to be affected with substance abuse.
set of alcohol problems and heritability of the prob- More recently, Bierut et al. (1998) have examined
lems. An association between early onset and herita- the familial nature of substance abuse in the Collab-
bility was found among male subjects, but not orative Study on the Genetics of Alcoholism
females. A study of twins in Australia has also sug- (COGA) sample. While COGA was designed to de-
gested a genetic influence in their drinking patterns, termine the genetic basis of alcoholism by using an
with a higher heritability among men than among extended-family study method, many of the persons
women (.66 h 2 vs. .42, h2 respectively) (Heath, in the sample with alcohol dependence were also af-
Meyer, Jardine, & Martin, 1991). fected with another comorbid substance use disorder.
Data from this six-site study indicate some specificity
of the familial nature of substance dependence, in-
Drug Abuse and Dependence
cluding alcohol dependence. In this study, the life-
Family pedigree studies have the potential to help to time prevalence of alcohol, marijuana, and cocaine
identify risk factors for other drug dependence as dependence was found to be higher in the biological
well as alcohol dependence, since they attempt to siblings of alcohol-dependent persons than in those
identify patterns of other substance abuse among bio- of control subjects, but an increased risk for mari-
logical relatives. However, only a few studies have juana or cocaine dependence in siblings was found
sought to determine a familial influence in the de- only when marijuana or cocaine dependence was
velopment of substance use disorders other than present in the probands. The risk of developing alco-
ethanol. Among this small group of studies some pat- hol dependence in the siblings was not increased by
terns seem to be emerging. Croughan (1985) re- comorbid substance dependence in probands.
viewed several family history studies and found that Several investigators have examined the role of
antisocial personality and criminality cluster in drug parents' influence on the drug of choice of their off-
dependence families, just as in families with alco- spring. A high concordance rate of tranquilizer use
hol dependence. Meuller, Rinehart, Cadoret, and (56%) between parent and child was found by Smart
Trough ton (1988) found a significant increase in the and Fejer (1972), while Annis (1974) found a posi-
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 53

tive relationship between adolescents' and parents' ton, Woodworth, and Stewart (1995) examined mul-
use of alcohol and painkillers. Although several stud- tipathways of transmission of these disorders from
ies of intergenerational drug use agree on the overall parent to offspring. Etiological pathways related to
impact of parental substance abuse, no consistency alcoholism, antisocial personality disorder, and drug
of findings for parents' influence on the drug of dependence were examined in a sample 95 male
choice by their offspring has been reported. adoptees in Iowa. In terms of the association between
While investigators seem to agree on the role of alcohol abuse and antisocial personality disorder,
genetic influences on the development of both alco- three independent pathways representing genetic and
holism and other drug abuse/dependence, separate environmental factors were found. The first pathway
genetic risk factors may affect the transmission of al- demonstrated a direct genetic effect of one or both
cohol dependence versus other drug dependencies. biological parents with alcoholism on the increased
Hill, Cloninger, and Ayre (1977) found that the risk for alcoholism among the biological offspring.
transmission of opioid dependence was independent The second pathway, indicating environmental fac-
of the transmission of alcoholism among the first-de- tors, showed a direct effect of alcohol problems in
gree relatives of subjects who were dependent on opi- adoptive relatives contributing to the increased risk
ates only, on alcohol only, and on both. Rounsaville, for alcoholism in adoptees. The third pathway, rep-
Weissman, Kleber, and Wilber (1982) compared the resenting antisocial personality disorder in the bio-
rates of drug abuse among the siblings of opiate ad- logical parent, showed an increased risk of an in-
dicts with or without a concurrent diagnosis of alco- tervening variable, antisocial personality disorder in
holism. Although the differences in the rates were adoptees. The presence of antisocial personality dis-
small, higher rates of drug abuse were reported by order, in turn, increased the risk for alcohol abuse/
the siblings of opiate addicts without alcoholism. dependency in adoptees.
Similarly, Stabenau (1992) found evidence suggest- Similarly, alcohol abuse/dependence in the bio-
ing that the risk for alcohol dependence was inde- logical parent increased the risk for drug abuse/de-
pendent of the risk for drug dependence in a sample pendence in adoptees, while antisocial personality
of 219 nonhospitalized nontreated young male and disorder in the biological parent increased the likeli-
female subjects. Further, it was found that antisocial hood of aggressivity associated with antisocial person-
personality disorder predicted alcohol abuse and de- ality disorder in the adoptees. Aggressivity functioned
pendence, family history of drug abuse predicted as an intervening variable for the development of
drug abuse/dependence, and additively, they pre- drug abuse and/or dependency in adoptees. Environ-
dicted lifetime rates of alcohol and drug abuse/de- mental factors, characterized by parental divorce or
pendence. separation as well as the presence of behavior prob-
lems in the adoptive parent, were also associated with
an increased risk for drug abuse/dependence in
Mechanisms of Heritability
adoptees (Cadoret et al., 1995).
The importance of the interaction between an inher- The separate and independent role of antisocial
ited vulnerability and environmental risk factors has personality disorder in the development of alcohol
been stressed by Kendler (1995). He places an empha- and other drug abuse/dependence found in the Ca-
sis on gene-environment interaction (G x E) rather doret et al. (1995) study is consistent with other pub-
than an "additive model," which assumes that the lished studies. Other investigators have demonstrated
impact of a pathogenic environment is independent that alcohol abuse/dependence and antisocial per-
of genotype. There is evidence from epidemiological sonality disorders in biological parents appear to be
studies that indicates a genetic influence on the self- transmitted to their offspring as separate traits, while
selection of individuals into high-risk environments both traits contribute to the risk of developing alco-
as well as supporting the role of environmental fac- holism and drug dependence in the offspring (Clon-
tors affecting the development of psychiatric disor- inger et al., 1978; Reich, Cloninger, Lewis, & Rice,
ders (Kendler, 1995). 1981). Further, the heritability of aggressive behav-
In their attempt to clarify genetic and environ- iors has also been documented. (Eron & Huessman,
mental contributions to the development of alcohol 1990; Mattes & Fink, 1987; Plomin, Nitz, & Rowe,
and other drug dependence, Cadoret, Yates, Trough- 1990). Similarly, conduct problems also distin-
54 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

guished children whose parents had antisocial per- Several investigators have found central nervous
sonality disorder from those children whose parents system disturbances, including impaired cognitive
did not (August & Stewart, 1983; Stewart, deBlois, & functioning and electrophysiological disturbances,
Cummings, 1980). Thus, conduct disorder, aggressiv- among persons affected with a substance abuse dis-
ity, and antisocial personality contribute to the risk order. Impairment of brain functioning as well as
of alcohol/drug abuse independent of each other and structural abnormalities have been reported among
independent of the risk due to parental alcohol/drug chronic alcoholics (Deckel, Bauer, & Hesselbrock,
abuse (Cadoret & Wesner, 1990; Hesselbrock et al., 1995; Hesselbrock et al., 1991). The areas of im-
1984, 1992; Loney, 1980). paired cognitive functioning include memory, atten-
A twin study by Lyons et al. (1995) also investi- tion span, visuospatial skills, abstract thinking, and
gated different mechanisms responsible for the famil- verbal reasoning. DeObaldia, Parsons, and Yohman
ial transmission of alcoholism by separating possible (1983), among others, reported an association be-
genetic factors from environmental factors. Symp- tween severe symptoms of alcohol dependence and
toms of antisocial personality disorder were ex- poor cognitive test performance among alcoholics.
amined in 3,226 male twin pairs. It was found that Electroencephalographic (EEG) and event-related
shared family environment was more important in potential (ERP) disturbances among alcoholics have
predicting the concordance of individual juvenile also been reported. Using event-related potential
symptoms, whereas genetic influences were more methods, Porjesz and Begleiter (1985) found reduced
important for predicting adult symptoms. P3 ERP waveform amplitudes among alcoholics as
compared to nonalcoholics. However, originally it
was not clear whether these differences represented
an indicator of risk for the development of alcohol-
Biological Factors in the Etiology of
ism or were the result of chronic heavy drinking.
Substance Use Disorders
Several studies of alcoholics have observed at least
some level of recovery in cognitive functioning fol-
Central Nervous System:
lowing abstinence.
Neuropsychological Functioning and the
Recent studies have provided evidence that elec-
Risk for Developing Alcoholism
trophysiological factors as measured by the EEG and
A variety of studies implicate heritable physiological ERP may contribute to the vulnerability to alcohol
factors associated with central nervous system func- dependence, independent of chronic alcohol con-
tioning in relation to an increased vulnerability to sumption. Begleiter et al. (1984) reported reduced
developing drug and alcohol abuse. Although the rel- P3 ERP component amplitudes, particularly over the
ative contribution of these specific inherited factors parietal area, among prepubescent, alcohol-naive
to an increased risk has not yet been identified, po- sons of alcoholic fathers compared to sons of nonal-
tential neurophysiological indicators of this vulnera- coholic fathers. These findings have been replicated
bility suggested in the literature include differences by other investigators (cf. O'Connor, Hesselbrock, &
in body sway (static ataxia; Lipscomb, Carpenter, & Tasman, 1986; V. Hesselbrock, O'Connor, Tasman,
Nathan, 1979), subjective feelings of intoxication, & Weidenman, 1988). Further, the amplitude of the
and an increased physiological response to ethanol P3 waveform has been shown to be related to aspects
(Schuckit, 1980, 1985; Schuckit, Gold, & Risch, of both figural memory and cognitive flexibility
1987). among young men at high risk for alcoholism (V.
Neuropsychological functioning has also been ex- Hesselbrock, Bauer, O'Connor, & Gillen, 1993). De-
amined as a risk factor. Aspects of neuropsychologi- spite these findings indicating the possible contri-
cal functioning are heritable, and it has been postu- bution of both electrophysiological and neuropsy-
lated that certain cognitive deficits among children chological factors to the development of alcohol
of alcoholics may contribute to the risk for develop- dependence, the relationship between electrophysio-
ing alcoholism and other substance abuse disorders logical measures and behavioral (neuropsychologi-
(see review by Hesselbrock, Bauer, Hesselbrock, & cal) measures of cognitive functioning are not well
Gillen, 1991). understood.
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 55

Deckel et al. (1995) examined neuropsychologi- or severe alcohol abuse in the probands and no his-
cal and electrophysiological measures in relation to tory of criminality or alcohol abuse in their biologi-
alcohol-related variables in young men at risk for al- cal fathers. Type 2 alcoholism is thought to be highly
coholism because of a positive family history of pater- heritable, male-limited (father-to-son transmission),
nal alcoholism. Neuropsychological tests measuring and developed independent of environmental fac-
frontal and/or temporal neocortical functioning were tors. It is characterized by moderate alcohol abuse in
found to be predictive of the age of taking their first the probands and severe alcohol use and criminality
drink and the frequency of drinking to get intoxi- in the fathers.
cated. Left-frontal slow-alpha EEC activity was also Bohman et al. (1981) examined female adoptees
associated with these alcohol-related variables. These in the Swedish sample and found only Type 1 alco-
findings suggest that disturbances in the integrity of hol abuse. However, only 31 female adoptees were
the anterior neocortex may be a risk factor in the identified who met criteria for alcohol abuse. A repli-
development of alcohol-related behaviors. cation study derived from a sample in Gothenburg,
Branchey, Buydens-Branchey, and Lieber (1993) Sweden, was reported recently by this study team
suggest that a low P3 amplitude could antedate sub- (Sigvardsson, Bohman, & Cloninger, 1996). The rep-
stance abuse and may be a risk factor for the develop- lication study essentially confirms the original find-
ment of substance misuse. They found that a subtype ings for both male and female adoptees.
of alcoholics with lifelong aggressive behavior exhib- The phenotypic characteristics of persons with a
ited lower P3 voltages in the event-related potential. family history of alcohol abuse in the Cloninger et
These patients were also characterized by a high ge- al. study are different from those reported by Good-
netic loading for alcoholism (Branchey et al., 1988, win (1979, 1984), who found a severe form of alco-
1993). While the number of subjects examined was holism among adoptee probands with a paternal his-
small (n = 10), low P3 amplitude was also observed tory of alcoholism. The differences in findings
among former cocaine and/or heroin addicts who between the two studies could be due to sample dif-
had been abstinent for at least 6 months. ferences, where the studies were conducted, and the
source of the information upon which parental clas-
sifications were made. In the Swedish study, a sub-
CLINICAL HETEROGENEITY AMONG ject was defined as having alcoholism based upon
ALCOHOL AND SUBSTANCE ABUSERS: two or more contacts with local temperance boards
IMPLICATIONS FOR ETIOLOGY or having been treated for alcoholism, while the
Danish study defined a subject as having alcoholism
based upon national hospitalization records.
Type I/Type 2
Both Swedish adoption studies are limited by the
The independent contributions of genetic factors rather small number of female alcohol abusers in-
and environmental factors to the development of al- cluded in the study, the restricted sample selection
cohol and drug addiction are difficult to separate. A methods, and the use of indirect measures of alcohol
primary reason for this difficulty is that neither alco- abuse for both the subjects and their fathers (Van-
hol nor other drug dependence is a unitary clinical clay & Raphael, 1990). Efforts to replicate the Swed-
disorder (Hesselbrock, 1986a, 1995). Both patient ish adoption study in the United States have resulted
and general populations of persons so affected are in equivocal support.
heterogeneous in relation to their clinical presen- Investigations of Type 1 and Type 2 alcoholism
tation. An early, influential attempt to subclassify in U.S. samples have found that the principal distin-
alcoholism was conducted in Sweden by the use of guishing etiological factor is the age of onset of alco-
retrospective data obtained from adoption records. holism. Type 2 alcoholism is characterized by an
Cloninger et al. (1981) proposed two forms of alco- early age of onset, while Type 1 is more prevalent
holism found among male adoptees based upon their among later onset alcoholics. While many alcohol-
own alcohol use and their parents' characteristics. related symptoms did not distinguish the two types of
The first form, Type 1, influenced by both genetic alcoholism among men treated at a VA hospital, the
and environmental factors, is characterized by mild age of onset of alcoholism was an important factor in
56 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

characterizing the two types of alcoholism (Penick et to Type A subjects, Type B cocaine abusers reported
al., 1990). Similar findings were reported by Irwin, higher rates of premorbid risk factors, including a
Schuckit, and Smith (1990) and von Knorring et al. family history of drug abuse, childhood behavior
(1987). problems, and an early age of onset of cocaine abuse.
Buydens-Branchey, Branchey, and Noumair (1989a) The course and consequences of the disorder among
also divided a sample of recently detoxified male al- Type B cocaine abusers were also more severe (i.e.,
coholic patients admitted to a rehabilitation program more severe drug and alcohol abuse, more addiction-
according to their age at the onset of alcoholism. related psychosocial impairment, more antisocial be-
Early-onset alcoholism included those patients who havior, and more comorbid psychiatric problems)
began alcohol abuse before 20 years of age, while than among Type A cocaine abusers.
the late-onset group had an onset of alcohol abuse
sometime after 20 years of age. The early-onset group
Gender Differences in Clinical
reported a higher prevalence rate of paternal alcohol-
Heterogeneity
ism and were twice as likely as the late-onset alcohol-
ics to have been incarcerated for crimes involving While typologies developed on the Swedish sample
physical violence. Further, the early-onset subjects and an empirically derived typology in the United
were found to be suffering from depression and were States seem to have etiological significance for the
more likely to have attempted suicide than the late- development of alcoholism for men, they do not nec-
onset alcoholics. Buydens-Branchey et al. (1989b) essarily apply to the women in the United States with
also suggested that early-onset alcoholics may have alcohol or other substance abuse problems. Unlike
a preexisting serotonin deficit, manifesting itself by the female subjects in the Swedish adoptee study,
increased alcohol intake at an early age. who were found to be of only one type (Type 1), a
female sample in the United States was found to in-
clude both Type 1 and Type 2 alcoholism. The Type
Type A/Type B
2 female alcoholics were characterized by early age
A more recent methodology of classifying alcoholics of onset, high familial density, and paternal alcohol-
and drug abusers was proposed by Babor et al. ism (Glenn & Nixon, 1991).
(1992). Using a cluster analysis of variables derived In another study with a small sample, Hessel-
from 17 different areas of clinical data, Babor et al. brock (1991) found that antisocial personality (ASP)
(1992) derived two types of alcoholism from 321 alcoholic women had characteristics similar to those
male and female hospitalized alcoholics. Two "types" of male Type 2 alcoholism. In order to further con-
of alcoholism were identified (Type A and Type B), sider possible gender differences, DelBoca and Hes-
which closely resembled Cloninger's Type 1 and selbrock (1996) conducted a reanalysis of the original
Type 2. Type A was also characterized by a late onset Type A and B (Babor et al., 1992) data set by deriv-
of alcoholism, while a principal characteristic of ing a four-cluster solution (vs. the original two-group
Type B alcoholism was an early onset of alcohol solution). As in the original analysis, the clusters ap-
problems and alcoholism. Further, the Type 2-like peared to separate, in part, along "risk" and "severity"
cluster (Type B) alcoholics displayed severe and dimensions. The risk dimension included vulnerabil-
chronic consequences of alcoholism and had a ity factors such as a family history for alcoholism,
higher frequency of childhood risk factors, familial early onset of alcohol problems, and a history of
alcoholism, and a more chronic treatment history. childhood conduct problems. The severity dimen-
Ball and colleagues (Ball, Carroll, & Babor, 1995; sion included indicators of physiological dependence
Feingold, Ball, Kranzler, & Rounsaville, 1996), using (tolerance and withdrawal), alcohol-related prob-
cluster-analytic methods to subclassify a nonclinical lems, and comorbid or alcohol-induced psychiatric
sample of cocaine abusers, found support for the symptoms (e.g., anxiety, affective disturbance). The
Type A and B classification of alcoholism among co- proportions of men and women found in the low
caine abusers. Their findings suggest that a multidi- risk-low severity group (39% women and 28% men)
mensional subclassification system may also have an and the high risk-high severity group (22% women
impact on our understanding of etiology and course and 22% men) were similar. The two intermediate
of both alcohol and other substance abuse. Relative subgroups were more gender-specific. The "internal-
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 57

izing" subtype, characterized by moderate risk and adulthood. More recently, Boyle et al. (1992) exam-
high alcohol involvement, included more women ined prospectively the association between conduct
than men. This group displayed a high level of de- disorder in early adolescence and substance use. The
pression and anxiety symptoms, but a low prevalence children were first assessed at 12-16 years of age re-
of ASP. The gender composition of the "externaliz- garding their substance use (e.g., tobacco, alcohol,
ers," with moderate risk and high severity, included marijuana, and hard drugs) and the presence of psy-
more men than women. The rate of ASP among sub- chiatric disorders (conduct disorder, attention deficit
jects in this subtype was high, while the prevalence disorder) and emotional problems (feelings of anxiety
of depression and anxiety was lower than in the other and depression). A follow-up assessment was con-
groups. These findings indicate the importance of ducted 4 years later. Even after controlling for poten-
gender considerations in the examination of the eti- tial confounding factors measured at the first assess-
ology and the clinical presentation of alcohol depen- ment (including drug use, attention deficit, and
dence. emotional disorder), Boyle et al. found that the asso-
ciation between conduct disorder in early adoles-
cence and marijuana and hard drug use in late ado-
PSYCHOPATHOLOGY, PERSONALITY, lescence remained statistically significant.
AND TEMPERAMENT AS RISK FACTORS It is difficult to delineate clearly a specific etiolog-
FOR ALCOHOL AND DRUG USE ical mechanism that ties childhood problem behav-
DISORDERS iors to the development of alcoholism or substance
abuse in adulthood. First, the concept of "childhood
problem behavior" includes a broad range of behav-
Association of Conduct Disorder and
ior problems in children, including hyperactivity,
Antisocial Personality Disorder as Risk
MBD, emotional problems, and deviant behavior
Factors for Alcoholism
(including vandalism, aggression, and hostility). This
The association of childhood behavioral problems constellation of behaviors has often been found to
and the development of alcoholism has been docu- predict substance use in adolescents, substance use
mented repeatedly in longitudinal studies of both problems in young adults, and onset and severity of
clinical and nonclinical samples over the past 30 a substance use disorder in adult patients. Most in-
years. The classic study conducted by Robins (1966) vestigators typically have not examined a broad, com-
found that childhood conduct problems predicted prehensive range of behavior problems. Instead, only
the later development of alcoholism in men treated some of the selected behaviors mentioned above
initially at a child guidance clinic as children. In an have been examined, and none have studied a com-
earlier study, McCord and McCord (1960) found prehensive list of behaviors/problems. Consequently,
that aggression and sadistic behaviors in delinquent it is difficult to identify a specific behavior(s) that in-
boys were predictive of the development of alcohol- fluences the development of substance abuse. Sev-
ism in adulthood. These findings have been repli- eral attempts have been made to identify clusters or
cated in longitudinal studies of community samples groups of risk behaviors that are related to the devel-
as well as in retrospective studies of adults with drink- opment of substance abuse. Windle (1996) found a
ing problems (Cahalan & Room, 1974; Jones, 1968). high intercorrelation among measures of different ex-
Childhood hyperactivity, when combined with ternalizing behaviors, including conduct disorder,
childhood conduct disorder, has been linked to adult attention deficit/hyperactivity disorder, and opposi-
alcoholism through studies of hospitalized alcohol- tional disorder, among teenagers. Further, teenaged
ics. Using a retrospective assessment, Tarter, Mc- moderate drinkers reported a higher frequency of
Bride, Buopane, and Schneider (1977) reported a these behaviors than light drinkers, and problem
higher frequency of childhood hyperactivity and drinkers reported more problem behaviors than mod-
minimal brain dysfunction (MBD) behaviors among erate drinkers, demonstrating a direct positive rela-
primary or "essential" alcoholics than among "reac- tionship between childhood problem behaviors and
tive" alcoholics. DeObaldia et al. (1983) also found both the level of consumption and the severity of
an association between hyperactivity/MBD in child- drinking problems in adolescents. M. N. Hesselbrock
hood and severe symptoms of alcohol dependence in (1986b) divided Tarter et al.'s (1977) list of problem
58 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

behaviors into hyperactivity, attention deficit, impul- socialization and aggressiveness (see review by
sivity, and conduct problems to examine their inde- Loeber & Dishion, 1983). Children who continue to
pendent contribution to the prediction of alcohol- be inattentive and impulsive are often characterized
ism. Only childhood conduct problems were related as aggressive, noncompliant, and antisocial and use
to a certain type of alcoholism in adulthood, namely, alcohol in their teens.
alcoholism with antisocial personality disorder. Simi- Importantly, persons who continue to use alcohol
larly, other investigators have found that conduct and drugs in their teens continue to use substances
problems also distinguished children whose parents as young adults .These results are supported by Kan-
were diagnosed with antisocial personality disorders del, Simcha-Fagan, and Davies (1986), who found
from those whose parents were not (August & Stew- that illicit drug use by boys during adolescence (ages
art, 1983; Stewart et al., 1980). 15-16) was a strong predictor of continued drug use
It may be of importance to differentiate conduct as long as 9 years later. Early drug use also predicted
disorder from attention deficit disorder, although later delinquent behavior among women. The find-
they frequently co-occur (Murphy & Barkley, 1996). ings of Kandel et al. suggest that gender differences
Boyle et al. (1992) found a significant independent influence the role played by delinquency, early drug
contribution of conduct disorder in predicting mari- use, and other problems as risk factors for adult sub-
juana and hard drug use among adolescents, but lit- stance use and misuse. Adult role deviations (e.g.,
tle evidence of an independent contribution of atten- unstable employment, not being married) were also
tion deficit disorder apart from conduct disorder. A identified as risk factors for illicit drug use in young
similar finding was reported by August and Stewart adulthood.
(1983).
A review of longitudinal developmental studies of
Temperament as a Risk Factor for
alcoholism indicates that antisocial behavior and dif-
Alcohol and Other Drug Abuse
ficulty in achievement-related activities in childhood
and adolescence are consistently related to the de- A search of the developmental process of childhood
velopment of alcoholism in adulthood (Zucker & problem behavior suggests that aspects of tempera-
Gomberg, 1986). The antisocial behavior cited in ment may predict both behavior problems and later
these studies included aggression, sadistic behaviors, substance abuse, particularly in adolescence. Tem-
antisocial activity, and rebelliousness, while the perament traits are expressed at an early stage of
achievement-related problems included poor school child development and seem to differentially predict
achievement, truancy, and dropping out of high boys' and girls' later behaviors. For example, a longi-
school. While Zucker and Gomberg's (1986) review tudinal study of very young children found that girls
found a link between childhood problems and the who were low in ego resiliency and ego control in
development of alcoholism, these factors were also nursery school were using marijuana at age 14, while
found among high-risk subjects who did not develop marijuana use in boys was predicted by low ego con-
alcoholism. trol, but not by early ego resilience (Block, Block, &
As also indicated by Zucker and Gomberg's re- Keyes, 1988).
view, not all children with behavior problems are Temperament has been identified as an impor-
destined to develop substance use disorders or antiso- tant factor in several theoretical formulations related
cial personality disorders in adulthood. Longitudinal to the development of pathological alcohol involve-
studies of hyperactive children found that many chil- ment (Cloninger, 1987; Lerner & Vicary, 1984;
dren diagnosed as hyperactive improve as they ma- Sher, 1991; Tarter, 1988). While prior research has
ture, although others do not (August & Stewart, shown that a predisposition to the development of
1983). Further, longitudinal studies of children with alcoholism is due partially to the individual's genetic
conduct problems indicate that only about one third makeup, several studies suggest that this genetic pre-
become antisocial adults (Robins, 1966; Robins & disposition may be expressed, in part, through the
Price, 1991). Violent and aggressive behavior typi- individual's temperament. Temperament characteris-
cally does not appear in adulthood if it has been ab- tics and extreme deviations in temperament charac-
sent in childhood. The distinguishing features of teristics have been found to be highly heritable (cf.
those who do not improve is the presence of under- Cloninger, 1987) and to manifest early in a child's
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 59

development. Studies of adolescent problem drinkers As described above, harm avoidance, novelty
have identified tolerance of deviance and related per- seeking, and reward dependence they are thought to
sonality traits (e.g., distrust, aggressive sociality, cyni- be genetically based and to be transmitted indepen-
cism) as being associated with acute alcohol prob- dently from parent to offspring, and they are thought
lems in adolescence. to represent variations in the individual's neurologi-
Currently, two of the more prominent theoretical cal makeup and influence susceptibility to the devel-
models of the development of alcoholism include opment of alcoholism. Although Cloninger has repli-
temperament as a key feature (Cloninger, 1987; cated his own findings in a separate Swedish sample
Cloninger & Gottesman, 1987; Tarter, 1988). In (Sigvardsson et al., 1996), few investigators have been
both models, temperament and personality charac- able to identify these three specific personality traits
teristics are linked to alcoholism through clusters of as distinguishing features of either alcohol-depen-
temperament and personality attributes that may be dent persons or high-risk subjects among U.S. sam-
transmitted from parents to their offspring. Cloninger ples (Hesselbrock & Hesselbrock, 1992; Masse &
(1987) has hypothesized that biologically based per- Tremblay, 1997).
sonality differences distinguish between Type 1 and Tarter and colleagues have proposed a broader
Type 2 alcoholism. Type 1 alcoholism was theorized temperament model of alcoholism. This model in-
to be associated with three heritable dimensions of cludes six dimensions of temperament that may be
personality: low novelty seeking, high harm avoid- inherited: activity level, attention span persistence,
ance, and high reward dependence. Type 2 alcohol- soothability, emotionality, reaction to food, and so-
ism was thought to be associated with the opposite ciability. Indeed, low attentional capacity, high emo-
spectrum of these personality characteristics. Masse tionality, and low sociability have been found to be
and Tremblay (1997) found that two of the personal- associated with an increased risk for developing alco-
ity traits of the Type lAType 2 typology are predictors hol-related problems (Tarter, 1988; Tarter, Kabene,
of early onset of substance use. In a study of kinder- Escallier, Laird, & Jacob, 1990). In addition, Lerner
garten boys, they found that high novelty seeking and and Vicary (1984), as well as Ohannessian and Hes-
low harm avoidance measured at age 6 predicted selbrock (1995), found that certain clusters of tem-
early onset of cigarette smoking, getting drunk, and perament traits, which constitute a "difficult temper-
other drug use in adolescence. Further, there was ament" (high activity level, low flexibility and task
some stability of the three traits from age 6 to age 10, orientation, mood instability, and social withdrawal),
with novelty seeking r= .38; harm avoidance r = .24; are related to substance use/abuse.
and reward dependence r = . 18 in a sample of about Mezzich et al. (1993) identified adolescents with
900 boys. alcohol abuse/dependence that could be clustered
Irwin et al. (1990) examined the usefulness of into two groups according to an internalizing/exter-
novelty seeking, harm avoidance and reward depen- nalizing behavior dimension. The first group was
dence for predicting alcohol-related problems among characterized by negative affect, while the second
young men whose fathers had alcohol problems, but group was better characterized by behavioral disturb-
they found no significant relationship between the ances, reduced depression, and anxiety symptoms
personality traits proposed by Cloninger and Gottes- (i.e., behavioral dyscontrol and hypophoria). The
man (1987) and either a family history of alcoholism second group also had increased substance use, in-
or the young men's drinking pattern (Irwin et al., creased problems at school and with peers, and in-
1990; Schuckit, Irwin, & Mahler, 1990). Hesselbrock creased behavioral problems. These findings provide
and Hesselbrock (1990) examined a sample of nonal- some confirmatory evidence for an adolescent typol-
coholic young adult men at high risk for developing ogy of alcohol dependence based upon personality
alcoholism. In addition, antisocial personality disor- factors that is similar to the Type A/Type B dichot-
der, regardless of a family history of alcoholism, was omy developed by Babor et al. (1992).
found to be an important factor in the prediction of More recently, personality research has focused
the development of alcohol use. Antisocial personal- upon what has been termed the five-factor model of
ity disorder was also associated with the three person- personality. This work traces its origins to Gordon
ality characteristics among young men at high risk Allport (1937) and Cattell (1947) and over the years
for developing alcohol abuse. has led to the identification of five robust factors:
60 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

(a) neuroticism—a tendency to experience negative they were 12-14 years old (Blackson & Tarter, 1994).
affect; (b) extroversion—gregariousness, activity; (c) Martin, Kaczynski, Maisto, and Tarter (1996) found
openness to experience—intellectual curiosity, aware- that dispositional traits characterized by heightened
ness of inner feelings, need for variety in actions; (d) negative affect (depressed mood and anxiety) and be-
agreeableness—altruism, emotional support, helpful- havioral undercontrol reflecting impulsivity, aggres-
ness; and (e) conscientiousness—will to achieve, de- sivity, acting out, and sensation seeking were signifi-
pendability, responsibility. These factors, which com- cant predictors of the number of drugs used by
bine aspects of the temperament traits proposed by adolescents. Assuming that "difficult temperament"
Cloninger and by Tarter as having etiological signifi- is predictive of adult antisocial personality disorder,
cance, consider the effects of more "normal" traits the findings of Martin et al. are supported by a study
rather than deviations. A study of the risk for alcohol- of unaffected young men in their early 20s which
ism in relation to the five-factor model of personality found that a diagnosis of antisocial personality disor-
found that a family history of alcoholism was posi- der was a more powerful predictor of heavy drinking
tively associated with openness and negatively as- (Hesselbrock & Hesselbrock, 1992).
sociated with agreeableness and conscientiousness Individual differences in temperament can be
(Martin & Sher, 1994). Alcohol use was positively conceptualized in terms of the developmental pro-
correlated with neuroticism and negatively correlated cess, along with the personality development of chil-
with agreeableness and conscientiousness. No inter- dren and adolescents. Rothbart and Ahadi (1994)
action was found between a family history of alcohol- proposed temperament as being constitutionally based
ism and gender in relation to the five dimensions and including an individual's reactivity (responsive-
of personality, nor was antisocial personality disorder ness of emotional activation and arousal systems) and
related to any of the five dimensions in subjects with development of ability for self-regulation, interacting
alcohol use disorders. over time with heredity, maturation, and experience.
Conversely, temperament may influence the way
children interact with their environment. Barren and
Association of Temperament and Conduct
Earls (1984) found that temperamental inflexibility,
Problems as Precursors to Substance Abuse
negative parent-child interaction and high family
The association between other aspects of children's stress showed a strong association with problem be-
temperament and conduct problems as precursors to havior in 3-year-old children. Others suggest that
substance abuse has been studied. "Difficult temper- temperament deviation in children may promote
ament disposition" or "temperament deviation" was maladaptive behavior and a tendency to associate
found to be associated with conduct disorder in with deviant peers. Deviation in temperament is also
childhood/adolescence, progressing to antisocial per- associated with aggression and poor responsiveness to
sonality disorder in adulthood, while "normative parental discipline, both of which are predictive of
temperament" was associated with time-limited de- conduct disorders (Blackson, 1994).
linquent behavior (Moffit, 1993; Windle, 1996). In
another study, 10- to 12-year-old sons of fathers with
and without substance abuse were separated by PSYCHOLOGICAL MODELS OF
means of a cluster analysis. The resulting two-cluster ETIOLOGY AND MAINTENANCE OF
solution classified boys along the dimensions of diffi- ALCOHOL AND DRUG USE DISORDERS
cult and normative temperament. The sons' temper-
ament cluster membership was a more salient pre-
Psychoanalytic Models
dictor of deviancy than a family history of substance
abuse. The boys classified as having difficult temper- Leeds and Morgenstern (1995) reviewed several the-
ament were high on aggressivity, maladaptive disci- ories of substance use that relate to various aspects of
pline, family dysfunction, attributional errors in per- psychoanalytic theory. Wurmser (1984) viewed sub-
ception of self, and high peer affiliations associated stance abusers as having severe intrapsychic conflict
with unconventionality and delinquent behavior. in the form of overly harsh superegos, so that these
Furthermore, these characteristics were predictive of individuals use alcohol or drugs to escape intense
the boys' alcohol and drug use 2 years later, when feelings of rage and fear. Khantzian, Halliday, and
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 61

McAuliffe (1990) took a self-deficit approach, posit- and Siegel (1979) noticed are often the opposite of
ing that inadequacies of the ego underlie substance the initial drug effects. Siegel called these unex-
abuse. This theory takes into account the notion that pected CRs "conditioned compensatory responses"
an individual's drug of choice has particular "self- (CCRs). The CCRs were noted to increase in strength
medicating" properties for his or her particular type with repeated trials, thus decreasing the observed
of ego deficit. Krystal's (1984) theory focuses on dis- drug effect (see Sherman, Jorenby, & Baker, 1988).
turbed object relations as the basis of substance Wikler (1973) also noticed that heroin addicts ex-
abuse/dependence and disturbed affective regula- hibited withdrawal symptoms simply by looking at
tion. McDougall (1989) proposed that all addictive paraphernalia associated with heroin use. He called
disorders are psychosomatic defenses against psychic this "conditioned withdrawal" and carried out a se-
conflict. ries of studies using heroin as the US, resulting in
In general, psychoanalytic models have been less withdrawal symptoms as the UR. The CS was the
widely accepted as underlying substance abuse/de- heroin-related paraphernalia, and the CR was an ex-
pendence, though they are thought-provoking and in- perience of withdrawal after the injection of an inert
teresting. The reader is referred to Morgenstern and substance (see also Rotgers, 1996).
Leeds (1993) and Leeds and Morgenstern (1995) for
more detailed discussion of psychoanalytic theories
Operant Conditioning
of etiology of substance use disorders.
Operant conditioning principles apply to the positive
reinforcing effects of alcohol and drugs as social rein-
Behavioral, Cognitive Behavioral, and
forcers, and to the avoidance or cessation of with-
Social Learning Theory Models
drawal symptoms. That is, an individual drinks in re-
Historically, behavioral models of substance use dis- sponse to an antecedent stimulus, such as a glass of
orders postulated that substance use behavior is beer or an angry mood, and then associates the rein-
learned and maintained through either classical or forcing effects of alcohol (i.e., euphoria or elevated
operant conditioning (chapter 14, this volume). The mood) with the antecedent stimulus. Substance-us-
contemporary cognitive behavioral (CB) models ing behavior increases as a result of the positive or
such as social learning theory (SLT) incorporate negative reinforcing effects of the alcohol or drug.
thoughts and feelings as important determinants of For instance, the putative effects of alcohol on
behavior and responses to the environment. Behav- tension reduction have been well documented. The
ioral and cognitive behavioral models are described literature documents variable effects of alcohol and
in detail in chapter 14 of this book and elsewhere drugs across different settings, individual characteris-
(Rotgers, 1996). Here, we will briefly review the ba- tics of drinkers, and different sources of stress. Recent
sic tenets of each approach to the etiology of sub- studies have conceptualized a self-medicating theory
stance abuse/dependence disorder. in terms of conditioned behavioral responses result-
ing from positive reinforcement received through the
consumption of alcohol and other drugs. Kushner,
Classical Conditioning
Sher, Wood, and Wood (1994) examined the moder-
Classical conditioning is thought to facilitate devel- ating effects of alcohol expectancies on tension re-
opment of a drinking or drug problem or craving duction, level of anxiety symptoms, and drinking be-
through pairing of conditioned stimuli (CS) such as havior among college students. A strong association
particular sites of use or people and the uncondi- between anxiety symptoms and alcohol consumption
tioned stimulus (US; alcohol or drugs), the result be- was found among men with high tension-reduction
ing a conditioned response (CR), or conditioned outcome expectancies, but not among women. How-
craving. ever, recent investigations of both clinical and non-
Conditioned tolerance has been proposed as a clinical samples have found anxiety disorders, while
classical conditioning paradigm, in which the sub- highly comorbid with alcohol and substance use dis-
stance is the US and the physiological effects are the orders, typically follow the development of alcohol
unconditioned response (UR); substance-related cues and other drug abuse rather than precede their de-
become the US, eliciting a CR which Wikler (1973) velopment (Hesselbrock, Hesselbrock, & Stabenau,
62 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

1985; Schuckit & Hesselbrock, 1995; Schuckit et al., description of the CB model of the etiology of sub-
1995). stance use disorders).
An example of a specific SLT is that of Petraitis,
Flay, and Miller (1995), who proposed the cognitive
Cognitive Behavioral/SLT Models
affective approach to explain adolescents' experimen-
Cognitive behavioral (CB) models highlight the im- tation with alcohol and other drugs. Their conceptu-
portance of cognitions and feelings as preceding and alization is based on a social learning theory which
directing behavior. Social learning theory (SLT) fo- asserts that the decision to experiment with sub-
cuses on constructs such as expectancies, self-effi- stances is influenced, in part, by the adolescent's be-
cacy, and attributions, all types of cognitions that are lief regarding the cost-benefit ratio of substance use.
thought to mediate the pathway from stimuli to use The process of forming the belief to using substances
of substances as response. Expectancies of the posi- progresses through several stages. The first cognitive
tive effects of substance use develop from repeated process is the evaluation that the costs are smaller
classical and/or operant pairings of the alcohol or than the benefits of substance use; this is followed by
drug with its reinforcing effects. Expectancies can be the formation of positive attitudes toward substance
thought of as conditioned cognitions, which can use and the perception that substance use is en-
themselves be associated with positive experiences, dorsed by the people around the adolescent. The au-
or positive subjective responses, to alcohol or drug- thors also cited the lack of self-efficacy in being able
related cues. Positive expectancies, such as expectan- to refuse alcohol/drug use as an important reason for
cies of relief from withdrawal symptoms or of relax- forming the decision to use substances.
ation following a drink, can facilitate more frequent
alcohol or drug use and thus contribute to the devel-
opment of dependence (see Rotgers, 1996). SOCIOCULTURAL MODELS OF
Self-efficacy, according to SLT, is an individual's ETIOLOGY AND MAINTENANCE
expectation or confidence in his or her ability to per-
form particular coping behaviors in certain situations
Familial Factors
and the expectation that the coping behavior will be
reinforced (see Rotgers, 1996, for a more detailed dis- As noted, alcohol and drug use disorders are multiply
cussion). Since SLT views substance use disorders as determined by a complex association of genetic, en-
a failure of coping, it is assumed that self-efficacy for vironmental, personality, and other factors. Because
coping without alcohol or drugs is low among active of these factors, often more than one family member
users, and this type of cognition contributes to in- is substance-dependent, which further complicates
creased use and development of dependence on the the task of teasing apart the specific influences that
substance. family environment, rearing, and interspousal rela-
CB theory postulates that initial heavy use of sub- tionships have on the development of alcoholism.
stances is the result of several interacting factors, Three contemporary models of family influence on
such as an individual's biological makeup (genetic the development and maintenance of substance de-
risk, temperament), which determines if the sub- pendence each take a different approach (see chapter
stance use will be reinforcing or punishing; the so- 16, this volume; McCrady & Epstein, 1996; Mc-
cial environment, which may facilitate or condone Crady, Kahler, & Epstein, 1998). The family disease
use; and the basic principles of operant conditioning, model posits that all family members suffer from a
which reward and maintain use. As an individual "family disease" of either alcoholism or codepen-
uses more, he or she uses other coping skills less and dency, and that alcoholism and codependency are
develops reduced self-efficacy and increased positive interrelated in such a way as to "enable" (perpetuate)
expectancies of the effects of the substance, the result the alcohol problem. Thus, according to this model,
being more use. In later stages, classical conditioning the specific etiology of the alcoholism is biological,
principles such as conditioned craving, tolerance, but the alcoholism is then maintained by a family
and withdrawal play an important role in the devel- disease.
opment and maintenance of heavy problem use of Research by means of the family systems model
alcohol or drugs (see Rotgers, 1996, for an excellent on the role of the family of origin of the drinker and
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 63

the spouse in the etiology of the substance abuse has adolescents for using alcohol were to socialize with
focused on family behavior around drinking. Origi- friends; to alleviate tension and anxiety, especially in
nally developed by Steinglass and associates (Davis, mixed-gender situations; to get high; to "cheer up";
Berenson, Steinglass, & Davis, 1974; Steinglass, and to reduce boredom.
Weiner, & Mendelson, 1971), the family systems It is not clear whether association with a deviant
model assumes that alcohol serves to stabilize family peer group is a risk factor for, or a result of, maladap-
equilibrium, and that families organize their interac- tive behavior. It has been suggested that adolescents
tions and structure around the alcohol to continue who abuse alcohol and drugs tend to associate with
the "homeostasis" (i.e., to maintain the alcohol prob- peers who are positive toward the abuse of alcohol
lem despite the problems associated with such a sys- and other drugs, providing support and reinforce-
tem). The degree to which alcoholic families uphold ment for these risky behaviors (Freeman & Dyer,
"family rituals" (e.g., dinnertime, celebration of holi- 1993; Harford & Grant, 1987). Furthermore, adoles-
days) may protect against development of alcoholism cents' deviant peer-group involvement interacts with
in offspring or at least may serve as a marker of trans- other risk factors, including family problems, stress
mission (Bennett, Wolin, Reiss, & Teitelbaum, 1987; and other mental health problems, and low self-es-
Steinglass, Bennett, Wolin, & Reiss, 1987; Wolin, teem. Thus, it can be difficult to separate etiological
Bennett, Noonan, & Teitelbaum, 1980). More re- factors from the consequences of substance abuse
cently, Bennett and Wolin (1990) reported that con- and other behavior problems (Freeman & Dyer,
tinuing interaction between alcoholic parents and 1993). Gender differences are evident, as males re-
their adult offspring is associated with increased rates port a higher rate of deviant peer involvement, pro-
of alcoholism among the male offspring. viding explanatory support for a higher rate of alco-
The third contemporary model is the behavioral hol and drug use in adolescent boys (Wills et al.,
family approach, which examines the family's (espe- 1992). Further, cultural differences seem to affect
cially the spouse's) behaviors as antecedents to and the differential influence of parental support for alco-
reinforcing consequences of substance use. These hol and drug abuse in young adults. Gillmore (1990)
behaviors serve to help develop and maintain the found that the initiation of alcohol, tobacco, and
drinking problem. This model is outlined in detail marijuana use, as well as the intention to use sub-
in chapter 16 of this book. stances as an adult, was also related to substance
availability and perceived parental approval, which
varied among Caucasians, Asian-Americans, and Af-
Peer Influences
rican-Americans.
Peer group influences have been cited consistently
as risk factors for the initiation of alcohol and other
Social Environments That Support
drugs among adolescents (Kandel, Kessler, & Mar-
Substance Use
gulies, 1978; Wills, Vaccaro, & McNamara, 1992).
Peers influence adolescents' behavior, values, and at- The social learning theories have relevance only
titudes. The association with deviant friends has within the context of both the micro- and the macro-
been found to promote the acceptance of deviant be- community. Petraitis et al. (1995) proposed a social
haviors (Loeber, Stouthamer, Van Kammen, & Farr- control theory which asserts that acceptance by or
ington, 1991) and to increase the risk for alcohol and attachment to family, school, or community is a so-
drug use among adolescents (Robins & McEvoy, cial bond to the conventional society. These social
1990). Further, peer relationships can either pro- bonds prevent adolescents from expressing deviant
mote or reduce the student's motivation for school behavior. According to this theory, the use of alcohol
performance and can affect self-esteem and social re- and other drugs is caused by a lack of social bonds.
lationships in adolescents (O'Connell, 1989). Segal Petraitis et al.'s conceptualization of social control
and Stewart (1996) found adolescents citing their theory regarding adolescents' experimentation with
perception of the positive aspects of substance use drugs and alcohol is supported by the work of Segal
involving peers, along with the tension reduction ef- and Stewart.
fects of alcohol, as reasons for alcohol/substance use. Segal and Stewart (1996) found that recent
In this study, the most important reasons cited by changes in cultural factors interact with individual
64 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

factors in the development of substance abuse. They ues and attitudes (Azzi-Lessing & Olsen, 1996). Fur-
noted that a cultural vacuum, produced by the de- thermore, the role of a particular culture as well as
clining role of family values, leads to the glorification the value system of a neighborhood, has been chang-
of fun and violence, as well as the use of alcohol and ing in recent years and plays a significant role in
drugs associated with promiscuous sexual practice, as the development of complex postindustrial society.
a means of escape from identity problems, frustra- These apparent changes are characterized as a de-
tion, disappointments, boredom, and so on. They cline in the support and interaction among neigh-
also regard the imitation of adult behavior, curiosity, bors, a weakening of the neighborhood's ability to
and a rebellion against age-related restrictions and ta- exert social control, social disorganization, and the
boos as reasons for adolescent drug use. These factors loss of a sense of continuity and belonging among
seem to apply both to the first experimental use of a neighborhood members. These social factors may re-
substance and to the development of the abuse of sult in an individual's increase in feelings of alien-
alcohol and drugs. Segal and Stewart view the abuse ation, narcissistic escapism, and deviant behavior
of alcohol and other drugs as being associated with (Segal & Stewart, 1996). Hawkins et al. identified a
more serious psychological factors but do not provide deterioration in parental socialization and supervi-
specific empirical support for their thoughts. sion, consistent with this explanation of neighbor-
Certain characteristics of neighborhoods also hood disorganization, as a risk factor in adolescent
seem to contribute to the development of problems drug abuse.
related to drug and alcohol use among their inhabit-
ants. Hawkins, Catalano, and Miller (1992) reviewed
several studies supporting the notion of "neighbor-
Socioeconomic Status as a Risk Factor
hood disorganization" as a risk factor for adolescent
drug abuse. This general term encompasses a variety Studies of the relationship between socioeconomic
of factors, including high population density, physi- status and alcohol and other drug abuse have found
cal deterioration, high levels of adult crime, and ille- a bimodal distribution of risk factors. Hawkins et al.'s
gal drug trafficking. (1992) review confirmed a positive correlation be-
Hawkins and Weis (1985) proposed a develop- tween parental education level and marijuana use
mental approach that integrates social control theory and drinking among teens. However, the poverty as-
and social learning theory as an etiological explana- sociated with childhood behavior problems has been
tion of delinquency. According to this approach, the found to increase the risk for later alcoholism and
person interacts sequentially with the smallest to the drug problems (Robins & Ratcliff, 1979). The rela-
largest social system. Thus, "social development" is a tionship of poverty to the development of drug abuse
process in which the most important units of social- could be explained by the environmental conditions
ization—families, schools, and peers—influence be- that define poverty, including unemployment, wel-
havior sequentially, both directly and indirectly. So- fare dependency, single parenthood, and an abun-
cial bonding and attachments to family, school, and dance of illicit drugs in the neighborhood (Gitlin,
the community increase the level of commitment to 1990). In a study of alcohol abuse/dependence and
conventionality among youths. However, youths de- associated patterns of psychiatric comorbidity in an
velop attachment and commitment to conventional- Ontario, Canada, household sample, Ross (1995)
ity only when they have opportunity to interact with found that high income was associated with pure al-
conventional activities that provide positive experi- cohol abuse, but not with alcohol dependence. Low
ences for them. The bonding of youths to the social income was associated with alcohol dependence
norms occurs only when the youths' association with complicated by comorbid psychiatric disorders. To-
conventional units is more rewarding than their asso- gether, these findings suggest a complex role of so-
ciation with delinquent peers. Thus, the value and cioeconomic status for both the etiology and the con-
activities of conventionality must be viewed as re- sequences of alcohol/substance use and abuse.
warding. Poor parenting skills and high levels of fam- Further research is needed to clarify the role of socio-
ily stress (often associated with parental substance economic status in relation to the level of severity
abuse) fail to provide children with conventional val- of use and abuse of substances, the specific types of
 ETIOLOGY OF ALCOHOL AND OTHER DRUGS 65

substances abused, and other possible etiological fac- alcoholic beverages are associated with decreased
tors, including comorbid psychopathology. drinking. Manning et al. (1991) reported that both
light and heavier drinkers appear to be less respon-
sive to price than moderate drinkers. However, Ken-
Social Policy Considerations
kel (1996) noted that this effect may be due to a lack
Social policy considerations, discussed in more detail of information about the health consequences of
in chapter 31 of this volume, can be considered heavy drinking among both the light and heavy
more distal factors related to the etiology of sub- drinkers rather than to concern over cost. In Kenkel's
stance abuse/dependence. Social policy influences study, better informed consumers showed greater re-
the availability of substances to the population and ductions in drinking due to price increases than less
the punitive effects of consuming particular sub- informed consumers, including heavy drinkers. The
stances. To some extent, lack of exposure and access use of taxation to increase the cost of obtaining alco-
to alcohol and drugs would serve as a protecting fac- hol is not straightforward. Federal taxes on alcohol,
tor against use, abuse, and development of depen- for example, are applied uniformly on each unit of
dence on substances. alcoholic beverage produced. However, different
Over the years, society (through governmental ac- manufacturers and different retailers operating in a
tion) has employed a variety of measures to restrict competitive market may choose to differentially pass
the availability of alcoholic beverages. Prohibition this cost along to the consumer. Thus, the cost of
enacted through an amendment to the U.S. Consti- alcohol may rise in some locales, but not in others.
tution at the national level, local and federal taxation Further, the cost of any particular brand of an
policies, and the legislation of minimum legal drink- alcoholic beverage may vary considerably within a
ing ages have had both short- and long-term effects specified geographic region, depending upon the
on the availability of beverage alcohol. Legal restric- type of establishment where the beverage is pur-
tions (e.g., based upon a minimum age) on the pur- chased. The package outlet price of a can of beer is
chase of alcohol have had recent favor as a means of typically lower than its cost at a restaurant, even
controlling adolescent morbidity and mortality re- though the unit tax is the same for both. This effect
sulting from alcohol use, apparently with some suc- may be manifested through an "ability to pay" in re-
cess. Between 1970 and 1975, when 29 states low- lation to younger drinkers. Sloan, Reilly, and Schen-
ered their minimum legal drinking ages, increases in zler (1994) estimated that the price of alcohol had a
teen alcohol consumption, auto fatalities, and injur- significant effect on motor vehicle fatalities among
ies were recorded. As the legal drinking age was 18- to 20-year olds, but not older age groups.
raised over the following years, reductions in adoles-
cent alcohol consumption (particularly beer), injur-
ies, and auto fatalities were generally noted (Wagen- SUMMARY
aar, 1993).The effect of raising the minimum
drinking age on the prevalence of other alcohol-re- This chapter reviewed a variety of etiological factors
lated behaviors among adolescents, such as assaults, that are related to development of alcohol and other
teen pregnancy, drownings, and sexually transmitted drug abuse. While the biological factors, including
diseases, is less clear as is the effect on the incidence genetics, and the neuropsychological factors have be-
of alcohol abuse and dependence in subsequent come increasingly important as etiological factors in
years. Such changes are difficult to determine di- the development of alcohol and other drug abuse
rectly because minimum drinking laws vary across problems, specific mechanisms of heredity are not
states, and because of the rather ready availability of known.
alcohol from other sources. Further, each biological factor interacts with per-
Taxation has also been viewed as a means of con- sonality, behavior, and development within the con-
trolling the availability of alcohol. The typical view text of environment in which a person grows up and
is that higher taxes on alcohol (resulting in an in- resides. Several environmental factors appear to af-
crease in unit price) lead to reduced consumption. fect the expression of genetic factors. For example, a
In general, increased taxes on (i.e., increased cost of) variety of studies indicate that peer influences, stress-
66 EPIDEMIOLOGY, ETIOLOGY, AND COURSE OF SUBSTANCE USE DISORDERS

ful and negative life events, and family environment Annis, H. (1974). Patterns of inter-familial drug use.
(including poor parenting styles) seem to enhance British Journal of Addiction, 69, 361-369.
the likelihood of developing alcohol or addictive August, G. }., & Stewart, M. A. (1983). Familial sub-
drug use behavior among adolescents and young types of childhood hyperactivity. Journal of Nervous
adults at high risk for developing problems with alco- and Mental Disease, 170, 147-154.
Azzi-Lessing, L., & Olsen, L. J. (1996). Substance
hol and other addictive substances. On the other
abuse-affected families in the child welfare system:
hand, certain social and environmental factors ap-
New challenges, new alliances. Social Work, 41(1),
pear to attenuate the risk for developing alcohol and
15-23.
drug use problems conferred by a family history of
Babor, T. F., Dolinsky, Z. S., Meyer, R. E., Hesselbrock,
alcoholism or drug abuse. Good relations with non- M. N., Hofmann, M., & Tennen, H. (1992). Types
drug-using peers, family rituals that actively seek to of alcoholics: Concurrent and predictive validity of
prevent alcohol/drug use, and consistency of parental some common classification schemes. British Jour-
discipline appear to reduce exposure to alcohol and nal of Addiction, 87, 1415-1431.
drugs among youth. Reduced exposure reduces the Ball, S. A., Carroll, K. M., & Babor, T. F. (1995). Sub-
likelihood that genes responsible for developing alco- types of cocaine abusers: Support for a type A-type B
holism or other drug use disorders will become acti- distinction. Journal of Consulting and Clinical Psy-
vated (Hesselbrock & Hesselbrock, 1990). chology, 63(1), 115-124.
The interaction between biological and environ- Barren, A. P., & Earls, F. (1984). The relation of tem-
mental factors is constantly changing, and new mod- perament and social factors to behavior problems in
els of etiology are being introduced. Prevention and three-year-old children. Jounal of Child Psychology
treatment efforts should consider these new develop- and Psychiatry, 25(1), 23-33.
Begleiter, H., Porjesz, B., Bihari, B., et al. (1984). Event
ments and evaluate their validity and applicability to
related brain potentials in boys at risk for alcoholism.
work with those who are affected.
Science, 225, 1493-1495.
Bennett, L. A., & Wolin, S. J. (1990). Family culture
and alcoholism transmission. In R. L. Collins, K. E.
ACKNOWLEDGMENT This work was supported by Leonard, & J. S. Searles (Eds.), Alcohol and the
NIAAA grants P50-AA35010 and U10-AA08403. Family: Research and Clinical Perspectives. New
York: Guilford Press.
Key References Bennett, L. A., Wolin, S. }., Reiss, D., & Teitelbaum,
M. A. (1987). Marital conflict resolution of alcoholic
Cadoret, J. J., & Wesner, R. B. (1990). Use of the adop- and nonalcoholic couples during drinking and non
tion paradigm to elucidate the role of genes and en-
drinking sessions. Journal of Studies on Alcohol, 40,
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183-195.
coholism. In C. R. Cloninger & H. Begleiter (Eds.),
Bierut, L. J., Dinwiddie, S., Begleiter, H., Crowe, R. R.,
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 II

Specific Drugs of Abuse:

Pharmacological and
Clinical Aspects
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 4

Alcohol

Darlene H. Moak
Raymond F. Anton

Among substances commonly abused by humans, al- hol; its actions in the central nervous system; the
cohol has by far the simplest structure, consisting of physical symptoms of use, abuse, and dependence;
only two carbon atoms, six hydrogen atoms, and a the symptoms and course of alcohol withdrawal; and
single oxygen atom. It is also a relatively "weak" drug, the pathological effects of its use. The diagnosis and
since grams of alcohol must be consumed in order treatment of the alcohol use disorders will be ad-
to achieve any measurable effect in contrast to the dressed in a subsequent chapters.
milligram (1/1000 gram) dosages of other abused
substances. Alcohol, in contrast to other abused sub-
stances, is a legal or licit substance (at least for per- MAJOR PHARMACOLOGICAL ACTIONS
sons over a certain age). Yet the misuse and abuse of
alcohol result in a complex biological, psychological,
Metabolic Pathways
and social disorder of enormous impact on society.
In 1993, the last year for which complete statistics Metabolism is the process by which the human body
are available, alcohol was believed to be responsible converts an ingested substance to other compounds
for 19,557 deaths, with an age-adjusted death rate of which are either more or less toxic than the parent
6.7 per 100,000 (Gardner & Hudson, 1996), and to compound. The primary metabolic pathway by
cost American society close to $100 billion annually which alcohol is detoxified, shown in figure 4.1, is
in loss of life, property, and productivity. "oxidation," most of which takes place in the liver.
This chapter will address the basic biological A small amount, about 5-10% of alcohol consumed
properties of this drug and its impact on human under normal conditions, bypasses this pathway and
function, including the metabolic pathways for alco- is excreted unchanged from the lungs or in the

75
76 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

FIGURE 4.1 Metabolism of alcohol via the major pathway, oxidation.

urine. Oxidation of alcohol in the liver is accom- (Tylenol) is also metabolized by CYP2E1, and in
plished through the action of the enzyme alcohol de- chronic heavy drinkers, there is evidence that acet-
hydrogenase, which converts alcohol to acetalde- aminophen use results in liver damage due to the
hyde. Acetaldehyde, in turn, is converted to acetate accumulation of toxic metabolites (Seeff, Cuccher-
by aldehyde dehydrogenase. This metabolic pathway ini, Zimmerman, Adler, & Benjamin, 1986). The
has been known since the 1940s. CYP2E1 system is also responsible for the metabo-
Although alcohol dehydrogenase is contained lism of many other medications, and the increased
largely in the human liver, it is also found in the activity of this system in chronic heavy drinkers typ-
lining of the stomach. Alcohol dehydrogenase in the ically results in lower blood levels for many impor-
stomach may play a major role in alcohol metabo- tant medications (Kalant, Khanna, Lin, & Chung,
lism (Haber et al., 1996), although the exact contri- 1976).
bution of this gastric component remains somewhat
controversial. Women appear to have less alcohol de-
Actions in the Central Nervous System
hydrogenase in the stomach lining than men and,
consequently, less activity of this enzyme (Frezza et
Impact on Neurotransmitter Systems
al., 1990). Thus, women may develop liver damage
after less extensive drinking careers than men be- Unlike other substances of abuse, which typically af-
cause of exposure of the liver to higher alcohol con- fect a particular transmitter system more strongly
concentrations. It is now known that there are at least than others (e.g., dopamine in the case of cocaine
eight subtypes, or isozymes, of human alcohol dehy- and the opioid system in the case of heroin), alcohol
drogenase in the liver alone (Ehrig, Bosron, & Li, is believed to affect many different neurotransmitter
1990), and many of the genes responsible for their systems, with no single system predominating. The
expression have been identified. findings of animal research have been reviewed re-
The enzyme aldehyde dehydrogenase has also cently by De Witte (1996). Acute alcohol consump-
been studied extensively. The widely used medica- tion in animals enhances release of serotonin,
tion disulfiram (Antabuse) exerts its effect on alcohol gamma aminobutyric acid (GABA), and taurine.
metabolism by inhibiting the activity of aldehyde de- However, chronic alcohol consumption decreases se-
hydrogenase. This inhibitor causes a buildup of the rotonin release and increases concentrations of en-
toxic metabolite acetaldehyde, which is normally dogenous opioid peptides and glutamate binding
present in only very small amounts in individuals sites. Most likely the reward pathways mediated by
consuming alcohol. This buildup, in turn causes a dopamine are also involved (Koob, 1992). Subtypes
distressing clinical syndrome characterized by ex- of receptors in each transmitter system probably play
treme flushing, nausea, and decreased blood pressure an important role in the initiation and maintenance
(the "disulfiram reaction"). Only two genetic variants of drinking behaviors.
of this enzyme have been identified. Most indi- The possible interactions of neurotransmitter sys-
viduals of Asian background have a variant with low tems and alcohol in the human brain have been ex-
activity, which results in poor tolerance of alcohol plored by Kranzler and Anton (1994) and are out-
consumption and relatively low rates of alcohol de- lined in table 4.1. A key tenet of these relationships
pendence (Mizoi et al., 1983). is that the dysfunctions in transmitter systems proba-
Alcohol is also metabolized via an alternative bly vary among subtypes of individuals affected by
pathway involving the liver enzyme cytochrome alcohol use disorders. Naltrexone, an opioid receptor
P450IIE1 (CYP2E1). This pathway exhibits in- blocker, has been found to be efficacious in the treat-
creased activity in individuals who have ingested al- ment of alcohol-dependent subjects, a finding that
cohol chronically (Lieber, 1994). Acetaminophen suggests the direct or indirect involvement of the opi-
 ALCOHOL 77

TABLE 4.1 Relationships of Alcohol and Neurotransmitter Systems

Neurotransmitter system Relationship to alcohol Possible clinical manifestations

GABA-A Enhanced activity with acute exposure Sedation

Desensitization with chronic exposure Withdrawal symptoms, seizures
Dopamine Increased release of dopamine (may be Stimulation of motor system, reinforcing
mediated by opioidergic mechanism) properties of alcohol
during acute exposure
Opioid Decreased basal levels of beta-endorphins Increased craving
in abstinent alcoholics and in children
of alcoholics
Inhibition of opioid receptor binding by Decreased alcohol consumption, de-
opioid antagonists creased tendency to relapse
Serotonin Alcohol causes increased serotonergic ac- Low serotonin levels in central nervous
tivity in brain (may "normalize"' low system may be associated with impul-
baseline levels) sivity and tendency toward violence
Serotonin agonists decrease alcohol in-
take in animals; inconsistent results on
alcohol intake in human studies
N-methyl-D-aspartate Inhibition of transmission with acute ex- None identified at this time
(NMDA) and glutamate posure to alcohol
Possible upregulation of NMDA recep- Behavioral tolerance
tors with chronic exposure to alcohol Seizures
Alcoholic dementia due to loss of
long-term potentiation (needed for
memory)

Note. From Kranzler and Anton (1994).

oid system (O'Malley et al., 1992; Volpicelli, Alter- alcohol. Tolerance has been shown to develop rap-
man, Hayashida, & O'Brien, 1992). An important idly in both animals and humans. Mechanisms un-
role for the serotonergic system is supported by find- derlying the development of tolerance in humans in-
ings of decreased metabolites of serotonin in the clude increasing the activity (induction) of the
cerebrospinal fluid of alcohol-dependent individuals enzymes responsible for the metabolism of alcohol
(Ballenger, Goodwin, Major, & Brown, 1979). Treat- as outlined above (metabolic tolerance), the ability
ment studies utilizing medications that alter seroton- of an organism to function in spite of the presence
ergic function have shown varying results, depending of alcohol (behavioral tolerance), and adaptation of
on the population studied (Kranzler et al., 1995; Sell- central nervous system cells to the effects of alcohol
ers, Higgins, Tompkins, & Romach, 1992). A new (neuronal tolerance) (Harris & Buck, 1990).
medication, acamprosate, which is believed to mod- Behavioral tolerance has been shown to be envi-
ulate the action of the excitatory amino acid gluta- ronmentally dependent in animals (Tabakoff & Mel-
mate, has been shown to be helpful in improving out- chior, 1981), since mice who developed tolerance in
comes (Sass, Soyka, Mann, & Zieglgansberger, 1996). one environment showed less tolerance in a novel
Ultimately, combinations of pharmacotherapy that environment. The N-methyl-D-aspartate (NMDA)
impact on several different neurotransmitter systems receptor may be particularly important in this pro-
may be of help in treating individuals with alcohol cess (Szabo, Tabakoff, & Hoffman, 1994).
use disorders. This approach will be explored in As a finding of great theoretical and practical in-
greater detail in chapter 19. terest, sons of alcoholics who show less intoxication
(i.e., demonstrate greater tolerance) when given a
single dose of alcohol are at higher risk of subsequent
Mechanisms of Tolerance
development of alcohol use disorders. This finding
and Dependence
suggests that more rapid development of tolerance in
Tolerance is defined as a reduction over time in the individuals with a family history of alcoholism may
behavioral effects after ingestion of the same dose of be genetically mediated (Schuckit & Smith, 1997).
78 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

While tolerance and physical dependence may When alcohol is consumed, it is first absorbed
share some mechanisms, there appear to be signifi- through the stomach wall. The rate at which it is
cant differences between these two processes as well. absorbed, and at which it subsequently enters the
Not all individuals who exhibit tolerance to alcohol general circulation, depends upon the concentra-
are physically dependent, and conversely, some indi- tion. Therefore, the alcohol in a strong drink is ab-
viduals who are physically dependent on alcohol sorbed more quickly than that in a weaker drink
may not display tolerance. Physical dependence on (Goldstein, 1992). Because absorption of alcohol in
alcohol occurs when central nervous system cells re- the stomach is slower than in the small intestine, ab-
quire the presence of alcohol to function normally. sorption can also be slowed by the presence of food
When alcohol intake is discontinued, there are clear in the stomach, which delays the emptying of the
signs of withdrawal. Although withdrawal can be stomach contents into the small intestine. Whatever
demonstrated after smaller doses of alcohol in both alcohol is not metabolized through "first-pass" me-
animals and humans (the typical "hangover"), a tabolism (either by alcohol dehydrogenase in the
more severe syndrome is seen after prolonged, stomach lining or by the liver) enters the general cir-
chronic use of alcohol. This syndrome will be more culation and reaches the brain, where it results in
fully described later in this chapter. characteristic behavioral effects (see below).
The propensity to develop physical dependence In general, the same dose of alcohol will result in
may also be genetically mediated. Different strains of a higher BAG in females than in males (Frezza et
mice have been bred which are differentially sensi- al, 1990; Sutker, Tabakoff, Goist, & Randall, 1983).
tive to withdrawal seizures (Phillips, Feller, & This effect is felt to be due largely to the smaller
Crabbe, 1989). Although the exact mechanism by proportion of body water in women than in men,
which physical dependence develops is not known, which leads to a smaller volume of distribution (Ar-
there is evidence to support a role for several differ- thur, Lee, & Wright, 1984) and to the decreased ac-
ent central nervous system pathways. These include tivity of alcohol dehydrogenase in the stomachs of
changes in neuronal membranes (Hunt, 1985); women. There is no predictable effect of menstrual
changes in excitability and function of nerve cells phase on blood alcohol concentration (Lammers,
mediated through the transport of charged atoms Mainzer, & Breteler, 1995).
(ions) especially calcium (Daniell & Leslie, 1986) Although the concentration of alcohol in a drink
and the GABA receptor/chloride channel (Allan & may affect the rate at which it is absorbed, it does
Harris, 1987); changes in the activity of excitatory not affect the total amount of alcohol delivered. A
neurotransmitter systems such as the glutamate sys- standard drink contains approximately 13.6 g of abso-
tem (Tsai, Gastfriend, & Coyle, 1995); and changes lute alcohol. A standard drink may therefore be 12
in "second messenger" systems (Gordon, Collier, & oz of beer containing 5% alcohol by volume, 5 oz of
Diamond, 1992). wine at 12% alcohol by volume, or 1.5 oz of hard
liquor containing 40% alcohol by volume. Since
"one drink" can mean quite different amounts to dif-
CLINICAL ASPECTS ferent people, it is important to use standardized
methodology when determining how much alcohol
Blood alcohol concentration is most commonly ex- an individual is consuming. A widely used method
pressed as milligrams of alcohol per 100 milliliters of is the time-line follow back (Sobell, Sobell, Klanjner,
volume, or milligrams percent. The level at which a Pavan, & Basian, 1986). The utilization of surrogate
social drinker might display symptoms of intoxication fluids (i.e., water) and standard glasses, allowing di-
is 100 milligrams percent, or .100. Alternatively, rect estimation of consumed volume, results in in-
blood alcohol concentration can be expressed as mil- creased accuracy for this method (Miller & Del
limoles per liter, in which case the level of intoxica- Boca, 1994).
tion becomes 10 millimoles per liter. The rate at which alcohol is eliminated from the
The absorption of alcohol from the gastrointesti- human body has been of interest because of its medi-
nal tract largely determines the rate of increase of the colegal implications, particularly in regard to opera-
blood alcohol concentration (BAG), the peak BAG tion of motor vehicles while under the influence of
that occurs, and the time at which the peak occurs. alcohol. Jones and Andersson (1996) studied blood
 ALCOHOL 79

samples from a large sample of individuals who had warfarin, barbiturates, benzodiazepines, phenothi-
been charged with driving under the influence and azines, and opiates. Conversely, chronic exposure to
found significantly higher rates of elimination for wom- alcohol results in increased activity, or induction, of
en (0.214 ±0.053 mg/ml/hr) than for men (0.189 ± this enzyme system, resulting in decreased levels of
0.048 mg/ml/hr). Of individuals in this study, 95% these medications. A few medications, such as ci-
had an elimination rate between 0.09 and 0.29 metidine and ranitidine (histamine H2-receptor an-
mg/ml/hr. This rate suggests that, since ingestion of tagonists), appear to be able to increase alcohol
one standard drink typically results in a blood alco- concentrations through inhibition of gastric alcohol
hol concentration of approximately 20 mg%, one dehydrogenase (DiPadova et al, 1992). Table 4.3
standard drink is eliminated in approximately 1 hr. shows interactions of both acute and chronic alcohol
The approximate blood alcohol concentrations for use with commonly used medications.
men and women resulting from ingestion of various Many individuals who abuse alcohol also abuse
amounts of alcohol and the decrease over varying other substances. A common abuse pattern is the
amounts of time are shown in table 4.2. combination of cocaine and alcohol. Cocaethylene,
an active metabolite of cocaine, is formed by concur-
rent use of alcohol and cocaine and has been found
Drug Interactions
to be pharmacologically similar to cocaine but is
Acute alcohol exposure tends to inhibit the CYP2E1 eliminated more slowly than cocaine (McCance,
enzyme system in the liver and thus to increase Price, Kosten, & Jatlow, 1995). In animals, cocaethy-
blood levels of many common medications, such as lene has been reported to cause increased lethality

TABLE 4.2 Blood Alcohol Concentrations (Milligrams Percent) by Gender,

Weight, and Number of Drinks Over Time

Males Females

Weight (Ib) Weight (Ib)

J50 200 250 100 120 J50

1 SD*a
After 1 hour 12 5 1 34 26 18
2SD
After 1 hour 40 32 18 84 67 51
After 2 hours 25 17 3 69 52 36
3 SD
After 1 hour 67 47 34 133 108 84
After 2 hours 52 32 19 118 93 69
After 3 hours 37 17 4 103 78 54
4SD
After 1 hour 95 67 51 183 149 117
After 2 hours 80 52 36 168 134 102
After 3 hours 65 37 21 153 119 87
After 4 hours 50 22 6 137 104 72
5 SD
After 1 hour 122 88 67 232 191 150
After 2 hours 107 73 52 217 176 135
After 3 hours 92 58 37 202 161 120
After 4 hours 77 43 22 187 146 105
After 5 hours 62 28 7 172 131 90

Note. Adapted from Fisher, Simpson, and Kapur (1987).

J
SD = standard drink as defined.
80 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

TABLE 4.3 Interactions of Alcohol With Commonly Used Medications

Medication Acute alcohol use Chronic alcohol use

Acetaminophen (Tylenol) Unclear Liver damage (can be fatal)

Nonsteroidal antiinflammatories Aspirin may increase effect of alcohol Damage to gastrointestinal tract (bleed-
(aspirin, Advil, etc.) ing, ulceration)
Benzodiazepines (Valium, etc.) Increased sedation Same
Decreased motor coordination
Anticonvulsants (Dilantin, etc.) Increased blood level and increased Increased risk of seizures
side effects
Antidepressants
Tricyclics Increased blood level (increased side ef- Decreased effectiveness due to de-
Serotonin uptake inhibitors fects) creased blood levels
Monoamine oxidase inhibitors Hypertensive reaction
Antipsychotics (Thorazine, etc.) Increased sedation Increased risk of liver damage
Anticoagulants (warfarin) Increased risk of bleeding Increased risk of blood clotting

Note. From National Institute on Alcohol Abuse and Alcoholism: Alcohol Alert (1995).

over cocaine (Hearn, Rose, Wagner, Ciarleglio, & individuals who abuse alcohol are more likely to die
Mash, 1991), but in humans, concurrent cocaine use from nicotine-related diseases than from the direct
was associated with decreased alcohol withdrawal effects of alcohol (Hurt et al., 1996). Since humans
symptoms (Castaneda, Lifshutz, Westreich, & Ga- may also develop cross-tolerance to alcohol and nico-
lanter, 1995) and a decreased risk of seizures (Moak & tine, exposure to nicotine-related stimuli may affect
Anton, 1996). However, inpatients who abused both craving of and relapse to alcohol (Monti et al., 1995).
cocaine and alcohol were found to be more de- Marijuana is also commonly used with alcohol,
pressed and to have higher global severity scores than and the combined effects of these two substances
inpatients who abused only cocaine (Brady, Sonne, have not been studied extensively. When normal
Randall, Adinoff, & Malcolm, 1995). subjects were administered the two substances either
Nicotine abuse also commonly occurs with alco- alone or together (Chait & Perry, 1994), additive ef-
hol use and abuse. While approximately one quarter fects on performance impairment and subjective
of the population of the United States has a history mood ratings were noted.
of tobacco dependence and one seventh has a history
of alcohol dependence (Anthony, Warner, & Kessler,
Physical Symptoms of Use,
1994), prevalence rates of smoking among alcohol-
Abuse, and Dependence
dependent individuals range from 71% to 97%, and
in contrast to trends in the general population, there In normal drinkers, acute alcohol use results in char-
has been no decrease in smoking rates in alcoholics acteristic effects at different BAG levels. Typically,
in the last two decades (Monti, Rohsenow, Colby, & mild euphoria is detected at levels of 30 mg/dl
Abrams, 1995). Furthermore, alcohol-dependent in- (mg%); mild incoordination at 50 mg/dl; ataxia, or
dividuals tend to smoke more heavily than nonalco- difficulty walking, at 100 mg/dl; and at 200 mg/dl,
holic smokers (Kozlowski, Skinner, Kent, & Pope, confusion and a reduced level of mental activity. At
1989). Nicotine has been shown to cause tolerance 300 mg/dl, most individuals have become stuporous,
to several effects of alcohol in mice, including hypo- and above 400 mg/dl, there is deep anesthesia (Vic-
thermia, open-field activity, and sleep time (Collins, tor, 1992).
Wilkins, Slobe, Cao, & Bullock, 1996). These find- Frequently, intoxicated individuals exhibit an in-
ings suggest that concurrent use of nicotine may ability to recall events that occurred during their
allow increased amounts of alcohol to be consumed drinking, a phenomenon known as a blackout. The
with less immediate adverse effects but without pro- precise mechanism by which blackouts occur is not
tection against long-term negative sequelae. In fact, known, although inhibition of N-methyl-D-aspartate
 ALCOHOL 81

(NMDA) receptor-stimulated calcium flux has been monly within 6-8 hr, and typically last 48-72 hr in
implicated (Diamond & Messing, 1994). Blackouts uncomplicated cases. DTs usually manifest between
are felt to be associated with more severe degrees of 48 and 96 hr after cessation of drinking and, with
alcohol misuse and may be an early warning sign of adequate treatment, usually last for 48-72 hr. Al-
developing abuse and dependence. though seizures typically occur within the first 24 hr
As mentioned previously, alcohol-abusing and after drinking ceases, they can occur up to 5 days
-dependent individuals frequently show less effect at afterward. At least two of the following symptoms are
each BAG mentioned above, as they have developed required to meet the definition of AW found in the
tolerance to the acute effects of alcohol. fourth edition of the Diagnostic and Statistical Man-
ual of Mental Disorders (DSM-IV): nausea and vom-
iting, tremor, sweating, anxiety and irritability, motor
Symptoms and Course of Withdrawal
arousal (agitation), skin sensations, heightened sensi-
There appears to be considerable interindividual tivity to light and sound, headache, and problems
variability in the presentation of alcohol withdrawal with concentration and orientation (Sellers, Sullivan,
(AW) symptoms. Individuals with quite similar drink- Somer, & Sykora, 1991). Increased blood pressure
ing careers may exhibit quite different degrees of and increased heart rate (pulse) are often found.
withdrawal symptoms, a finding that again suggests Most individuals with AW also exhibit decreased ap-
the strong influence of individual genetic vulnerabil- petite and abnormal sleep architecture. A commonly
ity to the withdrawal syndrome. The typical hangover used rating instrument that measures the intensity of
is a mild form of AW. Severe, life-threatening with- AW symptoms reliably is the Clinical Institute With-
drawal accompanied by loss of orientation and hallu- drawal Assessment for Alcohol (revised) (CIWA-Ar;
cinations is known as delerium tremens (DTs). DTs Sullivan, Sykora, Schneiderman, Naranjo, & Sellers,
occur in less than 5% of individuals with AW, and 1989). Scores over 10 on this scale generally indicate
mortality resulting from this syndrome when un- withdrawal that should be managed with medication
treated is estimated to be 15% (Victor, 1992) but is and supportive care.
less than 2% when the syndrome is recognized and Although many clinicians and researchers believe
treated properly (Ozdemir, Bremner, & Naranjo, that there is a "protracted" AW syndrome, defined as
1993). AW symptoms that persist after the first several days
Delerium tremens is more likely to occur in med- of cessation of drinking, the nature of this syndrome
ical settings, a finding that suggests that other organ remains ill defined. Abnormalities in brain function,
pathology, such as pancreatitis, pneumonia, and hep- as demonstrated in electroencephalographic (EEC)
atitis, may predispose toward the development of sleep recordings and positron emission tomography
DTs (Thompson, 1975). Seizures may occur during (PET) scans, lasting at least several weeks after drink-
withdrawal from alcohol, most likely occurring in 5- ing has been discontinued, have been documented
15% of alcohol-dependent individuals (Victor & (Gillin, Smith, Irwin, Kripke, & Schuckit, 1990; Vol-
Brausch, 1967). Seizure risk increases as daily intake kow et al., 1994) and support the notion that more
of alcohol increases, with an approximately 3-fold in- subtle AW symptoms may continue to affect alcohol-
crease in risk at 51-100 g alcohol/day (4-8 standard ics. Distinguishing possible protracted AW symptoms
drinks/day), an 8-fold increase in risk at 101-200 g/ from the symptoms and signs of other psychiatric dis-
day (9-14 standard drinks/day), and an almost 20- orders, such as affective and anxiety disorders, re-
fold increased in risk at more than 200 g/day (more mains challenging.
than 14 standard drinks/day) (Ng, Hauser, Brust, & There are many effective pharmacological treat-
Susser, 1988). When seizures are due solely to alco- ments for AW that are discussed in chapter 19. There
hol withdrawal, ongoing treatment with standard an- is increasing evidence that repeated episodes of AW
ticonvulsant medication is usually not required, in lead to more serious AW symptoms in subsequent
contrast to requirements for seizures associated with episodes (Booth & Blow, 1993; Brown, Anton, Mal-
idiopathic or posttraumatic epilepsy (Rathlev et al., colm, & Ballenger, 1988; Moak & Anton, 1996)
1994). which may be due to a "kindling" or sensitization
AW symptoms usually begin within 24-48 hr of phenomenon as originally hypothesized by Ballenger
decreasing or discontinuing drinking, most com- and Post (1978). If the severity of AW episodes is
82 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

mediated by a kindling process, anticonvulsants such new information. Confabulation, which is character-
as carbamazepine and valproate might reduce the ized by verbal responses that are grossly inaccurate
progressive worsening of AW symptoms over re- and often bizarre and fantastic, is common as an at-
peated AW episodes better than benzodiazepines, tempt to partially compensate for the defect. Korsa-
which are the current standard treatment. Research koff s psychosis is permanent in 25% of individuals
to define the role of these medications in the treat- in which it develops. Both of these severe syndromes
ment of AW is ongoing. can largely be prevented by the prompt administra-
Not all episodes of AW may require pharmaco- tion of thiamine, either orally or by intramuscular
logical treatment. Concern has been expressed re- injection, in individuals entering alcohol withdrawal.
garding the use of medications which themselves Many alcoholics develop a cerebellar syndrome
possess addictive potential, such as the benzodiaze- with profound ataxia, more pronounced in the legs
pines, in the treatment of a substance use disorder. than in the arms. Chronic use of alcohol also appears
A small but well-designed study by Naranjo and col- to lead to a typical dementia, with clinical manifesta-
leagues (1983) of alcoholics with mild to moderate tions of cognitive deficits including memory impair-
AW symptoms showed similar outcomes for both ment and pathological findings of cortical atrophy,
pharmacological and nonpharmacological treatment. enlargement of the lateral ventricles, and a loss of
More research is needed to better define the optimal cortical neurons. Modern brain-imaging techniques
use of medications in the treatment of AW episodes. bear promise in better defining the changes that oc-
cur and their possible resolution with abstinence
from alcohol (Mann, Mundle, Strayle, & Wakat,
PATHOLOGICAL EFFECTS 1995).
Polyneuropathy is the most common neurological
complication in alcoholism. Affected individuals com-
Physiological Effects
plain of numbness (paresthesias), pain, and weakness,
Organ systems that are particularly vulnerable to the especially in the feet. This can be severe enough to
adverse effects of excessive alcohol use are the cen- interfere with walking. Finally, an acute and even
tral nervous system; the gastrointestinal system, in life-threatening myopathy can occur after binge
particular the liver, and the cardiovascular system. drinking, with muscle swelling, weakness, and pain;
Table 4.4 summarizes the clinical syndromes that elevated blood levels of creatine kinase; and myoglo-
are a result of the toxic effects of alcohol. binuria, which can result in kidney damage. A more
chronic, usually painless, and commonly undiag-
nosed myopathy can also develop.
Central Nervous System

The alcohol withdrawal syndromes, which are mani-

Gastrointestinal System and Liver
festations of alcohol's toxicity on the central nervous
system, have already been discussed. Additionally, Alcohol is detoxified primarily in the liver and affects
chronic exposure to alcohol can give rise to a num- this organ in a number of ways (French, 1996). Alco-
ber of more pervasive neurological syndromes. Some hol appears to induce a hypermetabolic state in liver
may be due to an interaction with nutrition, such cells (hepatocytes), which results in a relative oxygen
as Wernicke's encephalopathy, caused by thiamine deficiency. This may in turn promote the formation
deficiency. Other disorders are most likely due to the of "free radicals" which lead to fibrosis (Ishii et al.,
direct neurotoxicity of alcohol, such as alcoholic de- 1996). Liver damage is first manifested by fatty
mentia and disorders of the nerves (neuropathy) and change (steatosis) which is reversible and clinically
muscles (myopathy) (Diamond & Messing, 1994). silent. This is followed by the development of alco-
Wernicke's encephalopathy is characterized by a holic hepatitis, which can present with jaundice, fe-
triad of ataxia (difficulty with walking), oculomotor ver, anorexia, and right upper quadrant abdominal
abnormalities (difficulty with eye movement), and pain.
global confusion (Reuler, Giard, & Cooney, 1985). Cirrhosis, or irreversible liver damage, is the most
It usually occurs in combination with Korsakoff s psy- severe form of alcoholic liver disease. It was the llth
chosis, which consists of a complete inability to learn leading cause of death in the United States in 1993,
 ALCOHOL 83

TABLE 4.4 Medical Disorders Caused by Alcoholism

Organ system Disorder

Central nervous system Wernicke's encephalopathy

Korsakoffs psychosis
Cerebellar ataxia
Alcoholic dementia
Polyneuropathy
Myopathy
Gastrointestinal system and liver Steatosis (fatty change)
Alcoholic hepatitis
Cirrhosis
Pancreatitis
Gastritis
Cardiovascular system Cardiomyopathy
Arrhythmias
Hypertension
Increased cholesterol and blood lipids
Decreased platelet aggregation
Endocrine system Hypoglycemia with acute exposure
Hyperglycemia with chronic exposure
Osteoporosis
Menstrual cycle irregularity in women
Decreased testosterone levels in men

although it ranked as high as 7th among women be- characteristic "flapping" tremor), fluctuating neuro-
tween the ages of 45 and 64 (Gardner & Hudson, logical signs, and distinctive changes on electroen-
1996). Cirrhosis appears to develop more quickly in cephalogram and is associated with elevated blood
women (Morgan, 1994), perhaps partly because of levels of ammonia. The hepatorenal syndrome, in
early exposure to higher levels of alcohol due to the which blood flow to the kidneys is critically de-
lower activity of gastric alcohol dehydrogenase. Con- creased, manifests clinically as a decreased urine pro-
comitant physical findings can include an enlarged duction and a retention of sodium and fluid.
spleen, abdominal fluid (ascites), testicular atrophy, The interaction of alcohol and viruses causing
enlarged breasts in males (gynecomastia), enlarged acute and chronic hepatitis is of great interest. Evi-
superficial blood vessels (spider angiomata), and pal- dence of hepatitis C virus infection, in particular, has
mar erythema. Frequently, the liver enzyme abnor- been found to be more common among individuals
malities characteristic of earlier stages of damage with alcoholic liver disease than in either patients
may actually normalize in cirrhosis, although a de- without alcoholism or patients with alcoholism but
crease in serum albumin and increase in serum glob- without alcoholic liver disease (Mendenhall et al.,
ulin may persist. 1991) and appears to be associated with more severe
Because cirrhosis causes obstruction of blood flow liver disease (Pares et al., 1990). An increased preva-
through the liver and increased pressure in the circu- lence of hepatitis B virus antibodies has been found
lation proximal to the liver (portal hypertension), in some studies as well (Brechot, Nalpas, & Feitel-
veins in the esophagus frequently become enlarged son, 1996). In addition to contributing to an acceler-
and are termed varices. These varices can bleed ated course of progression to cirrhosis, infection with
spontaneously and lead to fatal gastrointestinal hem- hepatitis viruses appears also to play a role in the de-
orrhage. Late complications of cirrhosis include he- velopment of cancer of the liver (Brechot et al.,
patic encephalopathy and the hepatorenal syndrome. 1996).
Hepatic encephalopathy is a complex neuropsychiat- Other gastrointestinal complications of excessive
ric syndrome consisting of disturbances in concious- alcohol use are inflammation of the pancreas, or
ness and behavior, personality changes, asterixis (a pancreatitis, and injury to the stomach lining, or gas-
84 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

tritis. The symptoms of pancreatitis are abdominal believed to result in a protective cardiovascular effect
pain, usually of a boring and steady quality and origi- (Gaziano et al., 1993). It is important to note that
nating in the upper abdomen with radiation through any positive effects of alcohol that have been docu-
to the back, and vomiting. Although most attacks are mented have occurred in individuals who are moder-
limited and last 2-3 days, severe attacks may result ate drinkers (less than three drinks per day) and that
in hospitalization, and there is a mortality of up to these benefits are quickly offset when drinking ex-
30%. Gastritis typically presents as pain in the upper ceeds truly moderate levels, currently defined as two
abdomen and vomiting of blood. While bleeding standard drinks per day for men and one standard
from gastritis is usually self-limited, it is important to drink per day for women.
distinguish it from bleeding from esophageal varices, Alcohol use also impacts the cardiovascular sys-
as described above. tem through its effect on platelet function (Re-
naud & Ruf, 1996). Platelets play a critical role in
blood clotting through their ability to clump at sites
Cardiovascular System
of injury. Alcohol has been shown to inhibit platelet
Alcohol has been known for over a century to have aggregation in both humans and animals. This may
a direct toxic effect upon the heart, having been be an underlying cause of the increased incidence of
first described in 1884 as occurring in persons who cerebral hemorrhages observed in alcoholics. It has
consumed large amounts of beer in Germany (the also been shown that, after heavy alcohol use, plate-
Munich "beer heart") (Rubin & Thomas, 1992). Al- lets will "rebound" and exhibit enhanced aggre-
though initially felt to be a manifestation of con- gation. This rebound aggregation may lead to an
comitant thiamine deficiency, it is now known that increased occurrence of cardiovascular events, in-
chronic use of alcohol results in a condition of heart cluding myocardial infarction, or heart attack, and
muscle weakening known as cardiomyopathy. This stroke. Interestingly, this rebound aggregation is not
condition may lead to irregular rhythms that some- observed in animals given red wine (Ruf, Berger, &
times result in sudden death (Ettinger et al., 1978). Renaud, 1995), in humans drinking red wine (Re-
Acute alcohol abuse can also result in deleterious ef- naud, Dumont, Godsey, Suplisson, & Thevenon,
fects on the heart. Kelly and colleagues (1996) found 1979), or when grape tannins are added to alcohol
decreases in heart muscle contractile force in healthy (Rufetal, 1995).
adult subjects at alcohol concentrations common
among social drinkers.
Endocrine System
Hypertension, or elevated blood pressure, is more
common among alcohol-abusing and -dependent in- Alcohol influences the function of several important
dividuals than in nonalcoholic members of the gen- hormonal and metabolic systems. In particular, it
eral population (Klatsky, 1996). This has been found can affect the metabolism of glucose and calcium
to be true for both sexes, across various age groups, and the function of the reproductive system. Acute
among different racial groups, and for drinkers of li- alcohol use can result in low blood sugar (hypoglyce-
quor, wine, or beer. Even though this relationship mia) through exhaustion of glycogen stores and inhi-
was first identified early in this century, the exact bition of glucose metabolism (Gordon & Lieber,
mechanism by which alcohol causes hypertension is 1992). Chronic heavy drinking is more likely to re-
not known. Some researchers have felt that hyperten- sult in elevated blood glucose (hyperglycemia) and
sion is a manifestation of mild alcohol withdrawal, can be especially harmful in those individuals who
while others have focused on the use of salt in the are predisposed to the development of diabetes melli-
diets of alcoholics. tus (Crane & Sereny, 1988).
Of importance in relation to these direct effects Alcohol interferes with calcium metabolism at
on the cardiovascular system is the effect of alcohol several levels. Acute alcohol use may lead to a tran-
on lipids (Frohlich, 1996). This has been an area of sient insufficiency of the important calcium regula-
some interest and also of controversy in recent years, tory glands, the parathyroids (Laitinen et al., 1991).
with several studies supporting a beneficial effect of This results in increased loss of calcium from the
moderate alcohol use on lipid profiles through in- body. Chronic alcohol use frequently leads to dietary
crease in high-density lipoprotein (HDL), which is insufficiency of calcium and vitamin D, which can
 ALCOHOL 85

lead to softening of the bones (i.e., osteoporosis). been suggested that such infant characteristics be
Liver disease, through alteration of reproductive hor- called alcohol-related birth defects (ARBD; Hanni-
mone levels, can also affect bone and calcium me- gan, Welch, & Sokol, 1992).
tabolism (Laitinen & Valimaki, 1993). In individuals The mechanisms by which alcohol use results in
with osteoporosis, the increased risk of falls associ- fetal effects are most likely complex. Four pathways
ated with alcohol use can result in an increased inci- have been suggested by Pratt (1984). Early in preg-
dence of fractures (Hingson & Rowland, 1987). nancy, alcohol acts as a direct teratogen, causing ei-
Many studies have found evidence of dysfunction ther cell death or chromosomal aberrations. Later in
of the reproductive system in heavy drinkers and al- development, between 4 and 10 weeks after concep-
coholics (Mendelson & Mello, 1988). Amenorrhea, tion, alcohol may act as a toxin to cells. Subse-
or absence of menstrual cycles, has been observed in quently, from 8 to 10 weeks onward, alcohol causes
women who drink heavily. Low levels of alcohol use disorganization and delay of cell migration and de-
(three to six drinks per week) in postmenopausal velopment. Finally, alcohol interferes with the pro-
women have been shown to be associated with in- duction of important brain transmitters and thus
creased levels of estradiol, which may result in a de- probably leads to behavioral problems. Growth defi-
creased risk of cardiovascular disease (Stampfer, Col- ciency may be mediated in part by alcohol effects on
ditz, Willett, Speizer, & Hennekens, 1988) but may growth hormone in these infants. Additionally, it has
also increase risk of breast cancer (Singletary, Dor- been suggested that alcohol use causes perinatal hy-
gan, Gapstur, & Anderson, 1996). Testicular func- poxia and acidosis in the fetus due to impairment
tion is also profoundly affected by heavy alcohol use, of umbilical circulation (Randall, Ekblud, & Anton,
with findings of decreased testosterone levels (Gor- 1990). It is not clear whether alcohol itself or its me-
don, Altman, Southren, Rubin, & Lieber, 1976) and tabolite acetaldehyde causes this effect.
the appearance of female sexual characteristics, such Longitudinal follow-up of infants and children
as enlarged breasts (Bannister & Lowosky, 1987). with FAS into adulthood is still in its early stages. It
has been shown that many children with FAS are
able to "catch up" in adolescence in regard to growth
Fetal Alcohol Syndrome
and that some of the facial anomalies resolve, but
Fetal alcohol syndrome (FAS) is very likely the most that maladaptive behaviors, including poor judg-
common known cause of mental retardation and af- ment, distractibility, and difficulty perceiving social
fects from 1 to 3 of every 1,000 infants born in the cues, persist (Streissguth et al., 1991).
United States. The risk to fetal health from alcohol It has been shown that increased maternal age is
has been recognized since the writing of the Bible, associated with greater fetal risk from alcohol use
and in 1899, a publication by Sullivan documented (Jacobson, Jacobson, & Sokol, 1996). Currently, the
an increased rate of stillbirth and infant death in the safest approach to alcohol use during pregnancy is
children of alcoholic women. believed to be the recommendation of complete ab-
The full manifestation of FAS is characterized by stinence. The possibility that such a stringent recom-
the triad of characteristic facial malformations, pre- mendation might unnecessarily alarm women who
natal and postnatal growth deficiency, and central may have drunk at very low levels during early preg-
nervous system dysfunction. Facial malformations in- nancy is of some concern (Abel, 1996).
clude short palpebral fissures (eye openings), elon-
gated midface, long and flat philtrum (area between
Psychological Effects
the mouth and nose), thin upper vermilion (lip), flat-
tened maxilla (cheeks), and flattening of the nasal Alcohol profoundly affects both affective states and
bridge (Sokol & Clarren, 1989). Central nervous sys- cognitive functioning. These effects can be seen in
tem involvement is demonstrated by findings of IQs social drinkers, in chronic heavy drinkers, in alcohol-
between 60 and 65, although a wide range is fre- ics, and in dually diagnosed individuals (those indi-
quently seen (Streissguth, Herman, & Smith, 1978). viduals with both an alcohol use disorder and an-
Infants who display some features of FAS but do not other psychiatric disorder). Relationships between
meet the full diagnosis were once described as hav- psychiatric symptomatology and alcohol use are very
ing fetal alcohol effects (FAE). More recently, it has likely complex and bidirectional; that is, alcohol use
86 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

results in characteristic affective changes, but preex- some cognitive functions, with verbal skills returning
isting affective disorders and expectancy sets may most quickly, usually within a month of attaining ab-
strongly influence the effect and pattern of drinking. stinence. Difficulties with abstraction and problem
Alcohol use disorders are more common among in- solving appear to be more long-lasting. Younger age
dividuals who meet criteria for affective and anxiety and length of abstinence are predictive of better re-
disorders (Kessler et al., 1997) than in individuals covery of cognitive functioning, while pattern and
without these disorders, but it is often not clear if the duration of alcohol use appear to be relatively weak
alcohol use disorder preceded or followed the onset determinants of cognitive impairment (Fein, Bach-
of the affective or anxiety disorder. Structured inter- man, Fisher, & Davenport, 1990). With continued
views that attempt to distinguish between so-called abstinence, scores on tests tend to improve but ap-
primary disorders (disorders that predate the onset of pear to remain inferior to those in age-matched con-
alcohol and other substance use disorders) and those trols.
disorders that occur secondary to substance use are
useful (Hasin et al., 1996).
Effects of Affective and Anxiety States
It is also crucial, when reviewing experimental
data, to be aware of the population being studied, as Many individuals, particularly heavier social drink-
it is likely that social drinkers and alcohol-abusing ers, use alcohol as a means to ameliorate uncomfort-
and -dependent individuals differ in important ways able affective and anxiety states (Lex, Mello, Mendel-
in their reasons for drinking and their response to son, & Babor, 1989). Because of alcohol's propen-
alcohol. sity to cause anxiety and depression, both through its
direct action on the central nervous system and
through subsequent withdrawal states, this "self-med-
Cognitive Effects
ication" with alcohol is likely to worsen existing psy-
The effect of alcohol on cognitive functioning in chological symptoms. Kushner, Sher, and Beitman
abusing and dependent populations is clearly a nega- (1990) found that while agoraphobia and social pho-
tive one. In social drinkers, however, the situation is bia were more likely to precede the onset of an alco-
not as clear. Individuals under the influence of alco- hol use disorder, panic disorder and generalized anx-
hol perform poorly on cognitive tests (Lex, Green- iety disorder were more likely to follow onset of
wald, Lukas, Slater, & Mendelson, 1988) but proba- alcohol abuse and dependence.
bly of greater interest is the long-term effect of Although depressive symptoms are common in
alcohol on cognitive performance of social drinkers. individuals with alcohol use disorders, these symp-
Important early studies (Hannon, Day, Butler, Lar- toms frequently remit with even short periods of
son, & Casey, 1983; Jones & Jones, 1980; Parker & abstinence (Brown & Schuckit, 1988). In some indi-
Noble, 1977) showed an association between de- viduals, particularly in women and in those experi-
creased performance on cognitive tasks and higher encing a disruption of social support, depressive dis-
levels of alcohol consumption among social drink- orders can occur independent of alcohol use and
ers. Other studies have been less supportive of a sig- persist after sobriety is achieved (Beck, Steer, &
nificant role of chronic alcohol use in decreased cog- McElroy, 1982; Overall, Reilly, Kelley, & Hollister,
nitive functioning, although recent heavy alcohol 1985). Suicide is a serious consequence of both alco-
intake was associated with mild cognitive defects hol use disorders and depression (Winokur & Black,
(Bergman, 1985). 1987), and suicide attempts by depressed alcoholics
Longitudinal studies have substantiated persis- are typically impulsive in nature, involving little if any
tently poorer performance on cognitive testing premeditation (Cornelius, Salloum, Day, Thase, &
among heavy drinkers than among social drinkers Mann, 1996). Suicide attempts are common among
and nondrinkers (Arbuckle, Chaikelson, & Gold, alcoholics, with 21% of men and 41% of women re-
1994). In abusing and dependent populations, defi- porting at least one lifetime attempt in one study
cits are observed in perceptual-motor skills, visual- (Hesselbrock, Hesselbrock, Syzmanski, & Weiden-
spatial performance, abstraction and problem solv- man, 1988). This report underscores the importance
ing, and learning and memory processes (Parsons & of assessing suicidality in individuals with alcohol use
Nixon, 1993). Abstinence does lead to recovery of disorders.
 ALCOHOL 87

It would also appear that personality attributes ics have been found to have interpersonal problem-
that are considered persistent and enduring may in solving deficits (Nixon, Tivis, & Parsons, 1992), and
fact change after the cessation of drinking, since the more improvement on a social skills task battery has
Minnesota Multiphasic Personality Inventory, as well been found to be associated with better adjustment
as the diagnostic criteria for personality disorders in alcoholics who were followed up 1 year after treat-
(SCID-P), shows change when repeated after a pe- ment (Jones & Lanyon, 1981). Since alcoholics have
riod of abstinence (Pettinati, 1990; Pettinati, Suger- been shown to have decreased functioning of the
man, & Maurer, 1982). prefrontal lobes of the brain (Volkow et al., 1992),
where social judgment and behavior or restraint are
mediated, it is possible that the impaired social func-
Expectancies of Alcohol Use
tioning, judgment, impulsivity, and lack of insight
In a study of a social drinking population interviewed manifested by actively drinking alcoholics are attrib-
by telephone, the typical reasons for alcohol use were utable to a direct toxic effect on the brain.
drinking to cope, drinking to be sociable, drinking to
enhance social confidence, and drinking for enjoy-
Family Function and Domestic Violence
ment (Smith, Abbey, & Scott, 1993). More positive
expectancies of alcohol use were found to predict Alcohol use and misuse are frequently associated
current drinking patterns and symptoms of alcohol with family dysfunction and domestic violence. Alco-
dependence in young adults (Williams & Ricciar- hol and other drug use by parents has been found to
delli, 1996). However, among "highly sexually inse- contribute to sexual and physical abuse of children,
cure" male and female college students, the expecta- although it is difficult at this time to estimate the
tion that alcohol would enhance sexuality did not extent of increased risk given the methodological
predict drinking patterns (Mooney, 1995). limitations of the studies that have been done, and
there is also evidence to support a link between the
experience of childhood violence and later alcohol
Social and Interpersonal Effects
and other drug abuse (Miller, Maguin, & Downs,
This section will discuss the relationship of alcohol 1997). Although homicides caused by domestic vio-
use and the following aspects of social functioning: lence were less likely to involve alcohol and drugs
impulsivity and lack of social restraint, family func- than homicides resulting from causes other than do-
tion and domestic violence, other forms of violence, mestic violence, the proportion of domestic violence
motor vehicle trauma and other trauma, work perfor- homicides in which substance use was involved
mance, and legal consequences. The important ef- (54%) was still high (Arbuckle et al., 1996). It is im-
fects of gender and age on the impact of alcohol use portant to assess substance use in the victim as well
on social functioning are considered in other sec- as in the perpetrator of domestic violence, since ex-
tions of this book. posure to trauma has been shown to be both a pre-
dictor and a consequence of alcohol use disorders
(Stewart, 1996).
Impulsivity and Lack of Social Restraint

Similar to the relationship of cognition and affect to

Motor Vehicle and Other Trauma
alcohol use as discussed above, the relationship of
social functioning to alcohol use appears to be bidi- Alcohol use also frequently plays a role in motor ve-
rectional. It is important, but sometimes difficult, to hicle accidents, burn injuries, and other trauma. Al-
distinguish the pathological effects of alcohol use on cohol intoxication, defined as a blood alcohol con-
social functioning from those deficiencies in social centration of 100 mg%, is associated with 40-50% of
functioning that can lead to problem drinking. In a traffic fatalaties, 25-35% of nonfatal motor vehicle
sample of young adult drinkers, low self-restraint, a injuries, and up to 64% of fires and burns (National
measure of social functioning, was a strong predictor Institute on Alcohol Abuse and Alcoholism [NIAAA],
of alcohol-related problems, especially when com- 1989). Burn victims who tested positively for alcohol
bined with a high level of distress (Weinberger & and other substances had significantly greater total
Bartholomew, 1996). Both male and female alcohol- body surface area involvement (McGill, Kowal-Vern,
88 SPECIFIC DRUGS OF ABUSE: PHARMACOLOGICAL AND CLINICAL ASPECTS

Fisher, Kahn, & Gamelli, 1995) and overall mortal- a crime (66% of the former group vs. 38% of the
ity (Haum et al., 1995; McGill et al. 1995). Interest- latter group) (Roslund & Larson, 1979). Based on
ingly, a stronger association was found between these statistics, rehabilitation of imprisoned individu-
drinking variables and injuries that resulted from vio- als that includes attention to treatment of substance
lence in a study of individuals requiring an emer- use disorders would seem to be appropriate, but stud-
gency room visit than for other frequent sequelae of ies of the effectiveness of such treatment programs
alcohol use, including motor vehicle accidents, pen- are lacking at the present time (Roesch, Ogloff, &
etrating traumas not caused by violence, and fires Eaves, 1995).
(Cherpitel, 1996).

SUMMARY
Occupational Performance

Alcohol use has long been believed to cause de- The consumption of alcoholic beverages can be a
creased work performance (Berry & Boland, 1977; pleasant aspect of many family and social activities,
U.S. General Accounting Office, 1970). However, and there is evidence that truly moderate alcohol use
many studies in this area have methdological flaws may offer some health benefits. However, the mis-
that have resulted in contradictory findings, suggest- use of alcohol, leading to the development of alcohol
ing a more complicated relationship between levels use disorders, has a negative impact on society at
of alcohol use and occupational performance (Webb many different levels. The medical disorders that re-
et al., 1994). Problem drinkers were found to be sult from excessive alcohol use are significant causes
more likely to sustain occupational injuries and to of morbidity and mortality. Psychological disturb-
have more absences due to these injuries (Hing- ances and social and interpersonal dysfunction
son & Rowland, 1987). Hangovers and drinking caused by or worsened by alcohol use result in im-
while at work were better predictors of work-related mense economic loss for society as well as human
problems than overall levels of drinking in a study of suffering that cannot be measured in dollars. Expo-
workers at a manufacturing facility (Ames, Grube, & sure of a fetus to alcohol extends the impact of alco-
Moore, 1997). Additionally, level of job satisfaction hol use disorders to future generations.
and belief in drinking as a coping mechanism were Research, both animal and human, which seeks
found to be important mediators of the effect of to improve our understanding of the action of alco-
drinking on work performance (Greenberg & Grun- hol at the molecular and biochemical level of the
berg, 1995; Webb et al., 1994). A study of the inter- central nervous system, as well as the development of
action of ethnicity and socioeconomic status on so- new psychotherapies and pharmacotherapies, offers
cial consequences of drinking found that less affluent hope to the millions of human beings affected by
black men had more drinking-related problems than these disorders.
less affluent white men, while affluent black men re-
ported fewer problems related to drinking than afflu-
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