The Health
Cdnsequences
Of Smoking

NICOTINE ADDICTION

a report of the
Surgeon General

1988

US. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health &vke
Cmlen for Disease Control
Cenlw for Healfh Plomofkn and Educatkn
Offke on Smoldng and Health
Rockvllk, Maryland 20857

For sale by the Superintendent of Documents, U.S. Government Printing Office
            Washingtoa, D.C. 20402


The Honorable James Wright
Speaker of the House
of Representatives
Washington, D.C.  20515

Dear Hf. Speaker:

I am pleased to transmit to the Congress the 1987 Surgeon General's Report on
the health consequences of smoking, as mandated by Section B(a) of the Public
Health Cigarette Smoking Act of 1969.  The Act requires the Secretary of
Health and Human Services to transmit a" annual report to Congress on the
health consequences of smoking and such recommendations for legislation as the
Secretary may deem appropriate.

This report, entitled The Health Consequences of Smoking: Nicotine Addiction,
examines the scientific evidence that cigarettes and other forms of tobacco
are addicting.  The issue of tobacco addiction has been addressed in previous
Surgeon General's Reports and in the medical literature beginning in the early
1900s.  Because of the recent expansion of research in this area, a thorough
review of this topic is warranted.  Despite the significant health risks of
tobacco use outlined in previous reports, many smokers have great difficulty
in quitting.  This report concludes that such difficulty is in large part due
to the addicting properties of nicotine, which is present in all forms of
tobacco.

The report further concludes that the processes that determine tobacco
addiction are similar to those that determine addiction to other drugs such as
heroin and cocaine.  Through such understanding, health-care providers may be
better able to assist tobacco users in quitting.

Private health organizations, health-care providers, community groups. and
government agencies should initiate or strengthen programs to inform the
public of the addicting nature of tobacco use.  A warning label on the
addicting nature of tobacco use should be rotated with other health warnings
now required on cigarette and smokeless tobacco packages and advertisements.
Preventing the initiation of tobacco use must be a priority because of the
difficulty in overcoming "icocine addiction once it is firmly established.
Because most cases of nicotine addiction begin during childhood and
adolescence, school curricula on the prevention of drug use should also
include tobacco.

Cigarette smoking, the chief avoidable cause of premature death in this
country, is responsible for mare than 300,000 premature deaths each year. The
disease impact of smoking justifies placing the problem of tobacco use at the
top of the public health agenda.  The conclusions of this report provide
another compelling reason for strengthening our efforts to reduce tobacco use
in our society.

                         Sincerely,
          f$&--- `4.y
                         Otis R. Bane", Y.D.
                         %YPZt*ry

Enclosure


The Honorable George Bush
President of the Senate
Washington, D.C. 20515

Deer Hr. Presfdent:

I am pleased to transmit t" the Congress the 1987 Surgeon General's Report an
the health consequences of smoking, as mandated by Section g(a) of. the Public
Health Cigarette Smoking Act of 1969.  The Act requires the Secretary of
Health and Human Services to transmit an annual report t" Congress on the
health consequences of smoking end such recommendations for legislation as the
Secretary may deem appropriate.

This report, entitled The Health Consequences of Smoking: Nicotine Addiction,
examines the scientific evidence that cirarettes and other forma of tobacco
are addicting.  The issue of tobacco addrction has been addressed in previous
Surgeon General's Reports end in the medical literature beginning in the early
1900s.  Because of the recent expansion of research in this area, a thorough
revi.& of this topic is warranted.  Despite the significant health risks of
tobacco "se outlined in previous reports, many smokers have great difficulty
in quitting.  This report concludes that such difficulty is in large part due
t" the addicting properties of nicotine, which is present i" all forms of
tobacco.

The report further concludes that the processes that determine tobacco
addiction are similar to those that determine addiction to other drugs such as
heroin and cocaine.  Through such understanding, health-care providers may be
better able to assist tobacco users in quitting,

Private health organizations, health-care providers, community groups. and
government agencies should initiate or strengthen programs to inform the
public of the addicting nature of tobacco use.  A vaming label on the
addicting "ature of tobacco use should be rotated vith other health warnings
now required on cigarette and swkelesa tobacco packages and advertisements.
Preventing the initiation of tobacco use must be a priority because of the
difficulty in overcoming "icotfne addiction once it is firmly established.
Because m"st cases of nicotine addiction begin during childhood and
adolescence, school curricula on the prevention of drug use should also
include tobacco.

Cigarette smoking, the chief avoidable cause of premature death in this
country, is responsible for more than 300,000 premature deaths each year. The
disease impact of smoking justifies placing the problem of tobacco use at the
top of the public health agenda.  The conclusions of this report provide
another compelling Peas"" for strengthening "UT efforts to reduce tobacco use
in our society.

Sincerely,

C&=5---&
Otis R. Boven, H.D.
Secretary


FOREWORD

This 20th Report of the Surgeon General on the health conse-
quences of tobacco use provides an additional important piece of
evidence concerning the serious health risks associated with using
tobacco.

The subject of this Report, nicotine addiction, was first mentioned
in the 1964 Report of the Advisory Committee to the Surgeon
General, which referred to tobacco use as "habituating." In the
landmark 1979 Report of the Surgeon General, by which time
considerably more research had been conducted, smoking was called
"the prototypical substance-abuse dependency." Scientists in the
field of drug addiction now agree that nicotine, the principal
pharmacologic agent that is common to all forms of t.obacco, is a
powerfully addicting drug.

Recognizing tobacco use as an addiction is critical both for treating
the tobacco user and for understanding why people continue to use
tobacco despite the known health risks. Nicotine is a psychoactive
drug with actions that reinforce the use of tobacco. Effort,s to reduce
tobacco use in our society must address all the major influences that
encourage continued use, including social, psychological, and phar-
macologic factors.

After carefully examining the available evidence, this Report
concludes that:

o Cigarettes and other forms of t,obacco are addicting.
o Nicotine is the drug in tobacco that causes addiction.
o The pharmacologic and behavioral processes that determine
   tobacco addiction are similar to those that determine addiction
  to drugs such as heroin and cocaine.
We must recognize both the potential for behavioral and pharma-
cologic treatment of the addicted tobacco user and the problems of
withdrawal. Tobacco use is a disorder which can be remedied
through medical attention; therefore, it should be approached by
health care providers just as other substance-use disorders are
approached: with knowledge, understanding, and persistence. Each
health care provider should use every available c!inical opportunity
to encourage or assist smokers to quit and to help former smokers to
maintain abstinence.


To maintain momentum toward a smoke-free society, we also must
take steps to prevent young people from beginning to smoke. First,
we must insure that every child in every school in this country is
educated as to the health risks and the addictive nature of tobacco
use. Most jurisdictions require that school curricula include preven-
tion of drug use; therefore, education on the prevention of tobacco
use should be included in this effort. Second, warning labels
regarding the addictive nature of t,obacco use should be required for
all tobacco packages and advertisements. Young people in particular
may not be aware of the risk of tobacco addiction. Finally, parents
and other role models should discourage smoking and other forms of
tobacco use among young people. Parents who quit set an example
for their children.

Smoking continues to be the chief preventable cause of premature
death in this country. Nicotine has addictive properties which help
to sustain widespread tobacco use. It is gratifying to see the decline
in reported smoking prevalence and cigarette consumption in the
United States during the past 25 years. However, we cannot expect
to see a sustained decline in rates of smoking-related cancers,
cardiovascular disease, and pulmonary disease without sustained
public health efforts against tobacco use.

The Public Health Service is committed to preventing tobacco use
among youth and to promoting cessation among existing smokers.
We hope that this Report will assist the health care community,
voluntary health agencies, and our Nation's schools in working with
us to reduce tobacco use in our society.

Robert E. Windom, M.D.
Assistant Secretary for Health

ii


PREFACE

This Report of the Surgeon General is the U.S. Public Health
Service's 20th Report on the health consequences of tobacco use and
the 7th issued during my tenure as Surgeon General. Eighteen
Reports have been released previously as part of the health
consequences of smoking series; a report on the health consequences
of using smokeless tobacco was released in 1986.

Previous Rep0rt.s have reviewed the medical and scientific evi-
dence establishing the health effects of cigarette smoking and other
forms of tobacco use. Tens of thousands of studies have documented
that smoking causes lung cancer, other cancers, chronic obstructive
lung disease, heart disease, complications of pregnancy, and several
other adverse health effects.

Epidemiologic studies have shown that cigarette smoking is
responsible for more than 300,000 deaths each year in the United
States. As I stated in the Preface to the 1982 Surgeon General's
Report, smoking is the chief avoidable cause of death in our society.

From 1964 through 1979, each Surgeon General's Report ad-
dressed the major health effects of smoking. The 1979 Report
provided the most comprehensive review of these effects. Following
the 1979 Report, each subsequent Report has focused on specific
populations (women in 1980, workers in 19851, specific diseases
(cancer in 1982, cardiovascular disease in 1983, chronic obstructive
lung disease in 19841, and specific topics (low-tar. low-nicotine
cigarettes in 1981, involuntary smoking in 1986).

This Report explores in great detail another specific topic: nicotine
addiction. Careful examination of the data makes it clear that
cigarettes and other forms of tobacco are addicting. An extensive
body of research has shown that nicotine is the drug in tobacco that
causes addiction. Moreover, the processes that determine tobacco
addiction are similar to those that determine addiction to drugs such
as heroin and cocaine.

Actions of Nicotine

All tobacco products contain substantial amounts of nicotine.
Nicotine is absorbed readily from tobacco smoke in the lungs and
from smokeless tobacco in the mouth or nose. Levels of nicotine in

. . .
111


the blood are similar in magnitude in people using different forms of
tobacco. Once in the blood stream, nicotine is rapidly distributed
throughout the body.

Nicotine is a powerful pharmacologic agent that acts in a variety
of ways at different sites in the body. After reaching the blood
stream, nicotine ent,ers the brain, interacts with specific receptors in
brain tissue. and initiates metabolic and electrical activity in the
brain. In addition, nicotine causes skeletal muscle relaxation and
has cardiovascular and endocrine (i.e., hormonal) effects.

Human and animal studies have shown that nicotine is the agent
in tobacco that leads to addiction. The diversity and strength of its
actions on the body are consistent with its role in causing addiction.

Tobacco Use as an Addiction

Standard definitions of drug addiction have been adopted by
various organizations including the World Health Organization and
the American Psychiatric Association. Although these definitions
are not identical, they have in common several criteria for establish-
ing a drug as addicting.

The central element among all forms of drug addiction is that the
user's behavior is largely controlled by a psychoactive substance (i.e.,
a substance that produces transient alterations in mood that are
primarily mediated by effects in the brain). There is often compul-
sive use of the drug despite damage to the individual or to society,
and drug-seeking behavior can take precedence over other important
priorities. The drug is "reinforcing"-that is, the pharmacologic
activity of the drug is sufficiently rewarding to maintain self-
administration. "Tolerance" is another aspect of drug addiction
whereby a given dose of a drug produces less effect or increasing
doses are required to achieve a specified intensity of response.
Physical dependence on the drug can also occur, and is characterized
by a withdrawal syndrome that usually accompanies drug absti-
nence. After cessation of drug use, there is a strong tendency to
relapse.

This Report demonstrates in detail that tobacco use and nicotine
in particular meet all these criteria. The evidence for these findings
is derived from animal studies as well as human observations.
Leading national and international organizations, including the
World Health Organization and the American Psychiatric Associa-
tion, have recognized chronic tobacco use as a drug addiction.

Some people may have difficulty in accepting the notion that
tobacco is addicting because it is a legal product. The word
"addiction" is strongly associated with illegal drugs such as cocaine
and heroin. However, as this Report shows, the processes that


determine tobacco addiction are similar to those that determine
addiction to other drugs, including illegal drugs.

In addition, some smokers may not believe that tobacco is
addicting because of a reluctance to admit that one's behavior is
largely controlled by a drug. On the other hand, most smokers admit
that they would like to quit but have been unable to do so. Smokers
who have repeatedly failed in their attempts to quit probably realize
that smoking is more than just a simple habit.

Many smokers have quit on their own ("spontaneous remission")
and some smokers smoke only occasionally. However, spontaneous
remission and occasional use also occur with the illicit drugs of
addiction, and in no way disqualify a drug from being classified as
addicting. Most narcotics users, for example, never progress beyond
occasional use, and of those who do, approximately 30 percent
spontaneously remit. Moreover, it seems plausible that spontaneous
remitters are largely those who have either learned to deliver
effective treatments to themselves or for whom environmental
circumstances have fortuitously changed in such a way as to support
drug cessation and abstinence.

Treatment

Like other addictions, tobacco use can be effectively treated. A
wide variety of behavioral interventions have been used for many
years, including aversion procedures (e.g., satiation, rapid smoking),
relaxation training, coping skills training, stimulus control, and
nicotine fading. In recognition of the important role that nicotine
plays in maintaining tobacco use, nicotine replacement therapy is
now available. Nicotine polacrilex gum has been shown in controlled
trials to relieve withdrawal symptoms. In addition, some (but not all)
studies have shown that nicotine gum, as an adjunct to behavioral
interventions, increases smoking abstinence rates. In recent years,
multicomponent interventions have been applied successfully to the
treatment of tobacco addiction.

Public Health Strategies

The conclusion that cigarettes and other forms of tobacco are
addicting has important implications for health professionals, educa-
tors, and policy-makers. In treating the tobacco user, health profes-
sionals must address the tenacious hold that nicotine has on the
body. More effective interventions must be developed to counteract
both the psychological and pharmacologic addictions that accompa-
ny tobacco use. More research is needed to evaluate how best to treat
those with the strongest dependence on the drug. Treatment of
tobacco addiction should be more widely available and should be

V


considered at least as favorably by third-party payors as treatment of
alcoholism and illicit drug addiction.

The challenge to health professionals is complicated by the array
of new nicotine delivery systems that are being developed and
introduced in the marketplace. Some of these products are produced
by tobacco manufacturers; others may be marketed as devices to aid
in smoking cessation. These new products may be more toxic and
more addicting than the products currently on the market. New
nicotine delivery systems should be evaluated for their toxic and
addictive effects; products intended for use in smoking cessation also
should be evaluated for efficacy.

Public information campaigns should be developed to increase
community awareness of the addictive nature of tobacco use. A
health warning on addiction should be rotated with the other
warnings now required on cigarette and smokeless tobacco packages
and advertisements. Prevention of tobacco use should be included
along with prevention of illicit drug use in comprehensive school
health education curricula. Many children and adolescents who are
experimenting with cigarettes and other forms of tobacco state that
they do not intend to use tobacco in later years. They are unaware of,
or underestimate, the strength of tobacco addiction. Because this
addiction almost always begins during childhood or adolescence,
children need to be warned as early as possible, and repeatedly
warned through their teenage years, about the dangers of exposing
themselves to nicotine.

This Report shows conclusively that cigarettes and other forms of
tobacco are addicting in the same sense as are drugs such as heroin
and cocaine. Most adults view illegal drugs with scorn and express
disapproval (if not outrage) at their sale and use. This Nation has
mobilized enormous resources to wage a war on drugs - illicit drugs.
We should also give priority to the one addiction that is killing more
than 300,000 Americans each year.

We as citizens, in concert with our elected officials, civic leaders,
and public health officers, should establish appropriate public
policies for how tobacco products are sold and distributed in our
society. With the evidence that tobacco is addicting, is it appropriate
for tobacco products to be sold through vending machines, which are
easily accessible to children? Is it appropriate for free samples of
tobacco products to be sent through the mail or distributed on public
property, where verification of age is difficult if not impossible?
Should the sale of tobacco be treated less seriously than the sale of
alcoholic beverages, for which a specific license is required (and
revoked for repeated sales to minors)?

In the face of overwhelming evidence that tobacco is addicting,
policy-makers should address these questions without delay. To

vi


achieve our goal of a smoke-free society, we must give this problem
the serious attention it deserves.

C. Everett Koop, M.D., Sc.D.
Surgeon General

vii


ACKNOWLEDGMENTS

This Report was prepared by the Department of Health and
Human Services under the general editorship of the Office on
Smoking and Health, Ronald M. Davis, M.D., Director. The Manag-
ing Editors were Thomas E. Novotny, M.D., and William R. Lynn,
Office on Smoking and Health.

Scientific editors were Neal L. Benowitz, M.D., Professor of
Medicine, Chief, Division of Clinical Pharmacology and Experimen-
tal Therapeutics, San Francisco General Hospital, University of
California, San Francisco, California; Neil E. Grunberg, Ph.D.,
Department of Medical Psychology, Uniformed Services University
of the Health Sciences, Bethesda, Maryland; Jack E. Henningfield,
Ph.D., Chief, Biology of Dependence and Abuse Potential Assessment
Laboratory, Addiction Research Center, National Institute on Drug
Abuse, Baltimore, Maryland; and Harry A. Lando, Ph.D., Professor,
Department of Psychology, Iowa State University, Ames, Iowa.

The following individuals prepared draft chapters or portions of
the Report.

David B. Abrams, Ph.D., Assistant Professor of Psychiatry and
Human Behavior, Brown University Program in Medicine, The
Miriam Hospital, Center for Health Promotion, Providence, Rhode
Island

Timothy B. Baker, Ph.D., Department of Psychology, University of
Wisconsin, Madison, Wisconsin

Neal L. Benowitz, M.D., Professor of Medicine, Chief, Division of
Clinical Pharmacology and Experimental Therapeutics, San Fran-
cisco General Hospital, University of California, San Francisco,
California

Thomas H. Brandon, M.S., Department of Psychology, University of
Wisconsin, Madison, Wisconsin

Richard F. Catalano, Ph.D., Research Assistant Professor, Center for
Social Welfare Research, School of Social Work, University of
Washington, Seattle, Washington

Larry D. Chait, Ph.D., Research Associate (Assistant Professor),
Department of Psychiatry, University of Chicago, Chicago, Illinois
Paul B.S. Clarke, Ph.D., Department of Pharmacology and Thera-
peutics, McGill University, Montreal, Quebec, Canada

ix


Richard R. Clayton, Ph.D., Professor, Department of Sociology,
University of Kentucky, Lexington, Kentucky
Allan C. Collins, Ph.D., Institute for Behavioral Genetics, School of
Pharmacy, University of Colorado, Boulder, Colorado
Thomas M. Cooper, D.D.S., Professor, Department of Community
Dentistry, University of Kentucky, Lexington, Kentucky
Lori A. Crane, M.P.H., Division of Cancer Control, Jonsson Compre-
hensive Cancer Center, University of California, Los Angeles,
California

Susan Curry, Ph.D., Center for Health Studies, Group Health
Cooperative of Puget Sound, Seattle, Washington
D. Layten Davis, Ph.D., Director, Tobacco and Health Research
Institute, University of Kentucky, Lexington, Kentucky
Ronald M. Davis, M.D., Director, Office on Smoking and Health,
Center for Health Promotion and Education, Centers for Disease
Control, Rockville, Maryland

Edward F. Domino, M.D., Professor, Department of Pharmacology,
University of Michigan, Ann Arbor, Michigan
John L. Egle, Jr., Ph.D., Department of Pharmacology/Toxicology,
Medical College of Virginia, Virginia Commonwealth University,
Richmond, Virginia

Joan Ershler, Ph.D., Research Associate, Mt. Sinai Medical Center,
Milwaukee, Wisconsin

Raymond Fleming, Ph.D., Assistant Professor, University of Wiscon-
sin-Milwaukee, Mt. Sinai Medical Center, Milwaukee, Wisconsin
Kathleen A. Fletcher, Ph.D., M.P.H., Consultant, The University of
Texas Health Science Center, Houston, Texas
Paul J. Fudala, Ph.D., Addiction Research Center, National Institute
on Drug Abuse, Baltimore, Maryland
C. Gary Gairola, Ph.D., University of Kentucky, Tobacco and Health
Research Institute, Lexington, Kentucky
David Gilbert, Ph.D., Department of Psychology, Southern Illinois
University, Carbondale, Illinois

Lewayne D. Gilchrist, Ph.D., Research Associate Professor, School of
Social Work, University of Washington, Seattle, Washington
Donna M. Goldberg, M.A., Annapolis, Maryland
Steven R. Goldberg, Ph.D., Preclinical Pharmacology Research
Branch, Addiction Research Center, National Institute on Drug
Abuse, Baltimore, Maryland

John Grabowski, Ph.D., Department of Psychiatry and Behavioral
Science, The University of Texas Health Science Center, Houston,
Texas

Neil E. Grunberg, Ph.D., Department of Medical Psychology, Uni-
formed Services University of the Health Sciences, Bethesda,
Maryland

X


Dorothy K. Hatsukami, Ph.D., Department of Psychiatry, University
of Minnesota, Minneapolis, Minnesota
J. David Hawkins, Ph.D., Professor, Center for Social Welfare
Research, School of Social Work, University of Washington,
Seattle, Washington

Jack E. Henningfield, Ph.D., Chief, Biology of Dependence and
Abuse Potential Assessment Laboratory, Addiction Research Cen-
ter, National Institute on Drug Abuse, Baltimore, Maryland.
Ronald I. Herning, Ph.D., Addiction Research Center, National
Institute on Drug Abuse, Baltimore, Maryland
Matthew Owen Howard, M.S., M.S.W., Research Assistant, Center
for Social Welfare Research, School of Social Work, University of
Washington, Seattle, Washington

John R. Hughes, M.D., Departments of Psychiatry, Psychology, and
Family Practice, University of Vermont, Burlington, Vermont
Edgar T. Iwamoto, Ph.D., Department of Pharmacology, College of
Medicine, University of Kentucky, Lexington, Kentucky
Murray E. Jarvik, M.D., Ph.D., The Neuropsychiatric Institute and
Hospital, School of Medicine, University of California, Los An-
geles, Veterans' Administration Medical Center, Brentwood Divi-
sion, Los Angeles, California

Robert C. Klesges, Ph.D., Associate Professor, Center for Applied
Psychological Research, Department of Psychology, Memphis
State University, Memphis, Tennessee
Lynn T. Kozlowski, Ph.D., Head, Behavioral Research on Tobacco
Use, Addiction Research Foundation, Professor of Psychology and
of Preventive Medicine and Biostatistics, University of Toronto,
Toronto, Ontario, Canada

Howard Leventhal, Ph.D., Professor and Chairman, Department of
Psychology, University of Wisconsin, Madison, Wisconsin
Edythe D. London, Ph.D., Chief, Neuropharmacology Laboratory,
Addiction Research Center, National Institute on Drug Abuse,
Baltimore, Maryland

Scott E. Lukas, Ph.D., Assistant Professor of Psychiatry (Pharmacol-
ogy), Harvard Medical School, Department of Psychiatry, Alcohol
and Drug Abuse Research Center, McLean Hospital, Belmont,
Massachusetts

Alfred C. Marcus, Ph.D., Associate Director, Division of Cancer
Control, Jonsson Comprehensive Cancer Center, University of
California, Los Angeles, California
Andrew W. Meyers, Ph.D., Professor, Center for Applied Psychologi-
cal Research, Department of Psychology, Memphis State Universi-
ty, Memphis, Tennessee

Thomas E. Novotny, M.D., Medical Epidemiologist, Office on Smok-
ing and Health, Center for Health Promotion and Education,
Centers for Disease Control, Rockville, Maryland

xi


Carol Tracy Orleans, Ph.D., Senior Investigator, Behavioral Medi-
cine and Director of Smoking Cessation Services, Division of
Cancer Control, Fox Chase Cancer Center, Philadelphia, Pennsyl-
vania

John P. Pierce, MSc., Ph.D., Chief, Epidemiology Branch, Office on
Smoking and Health, Center for Health Promotion and Education,
Centers for Disease Control, Rockville, Maryland
Ovide F. Pomerleau, Ph.D., Behavioral Medicine Program, Universi-
ty of Michigan, Department of Psychiatry, Ann Arbor, Michigan
Amelie G. Ramirez, M.P.H., Faculty Associate, The University of
Texas Health Science Center, Assistant Professor, Baylor College
of Medicine, Houston, Texas

Jed E. Rose, Ph.D., Veterans' Administration Medical Center,
Wadsworth and Brentwood Divisions, Los Angeles, California
J.A. Rosecrans, Ph.D., Department of Pharmacology, Medical Col-
lege of Virginia, Virginia Commonwealth University, Richmond,
Virginia

David P.L. Sachs, M.D., Director, Smoking Cessation Research
Institute, Palo Alto, California

Mary Anne Salmon, Ph.D., Research Associate, Health Services
Research Center, University of North Carolina, Chapel Hill, North
Carolina

Nina G. Schneider, Ph.D., Associate Research Psychologist, Depart-
ment of Psychiatry and Biobehavioral Sciences, UCLA School of
Medicine, Research Psychologist, Psychopharmacology Unit, Vet-
erans' Administration Medical Center, Brentwood Division, Los
Angeles, California

V.J. Schoenbach, Ph.D., Associate Professor, Department of Epide-
miology, Research Associate, Health Services Research Center,
University of North Carolina, Chapel Hill, North Carolina
Saul Shiffman, Ph.D., Associate Professor, Department of Psycholo-
gy, University of Pittsburgh, Pittsburgh, Pennsylvania
Victor J. Strecher, Ph.D., Research Associate, Health Services
Research Center, Assistant Professor, Department of Health
Education, University of North Carolina, Chapel Hill, North
Carolina

David M. Warburton, Professor, Department of Psychology, Univer-
sity of Reading, Whiteknights, Reading, United Kingdom
Elizabeth A. Wells, Ph.D., Post-Doctoral Fellow, Center for Social
Welfare Research, University of Washington, Seattle, Washington
Thomas Ashby Wills, Ph.D., Assistant Professor of Psychology,
Assistant Professor of Epidemiology and Social Medicine, Depart-
ment of Epidemiology and Social Medicine, Ferkauf Graduate
School of Psychology and Albert Einstein College of Medicine,
Bronx, New York

xii


Phillip P. Woodson, Dr.sc.nat., Addiction Research Center, National
Institute on Drug Abuse, Baltimore, Maryland

The editors acknowledge with gratitude the following distin-
guished scientists, physicians, and others who lent their support in
the development of this Report by coordinating manuscript prepara-
tion, contributing critical reviews of the manuscript, or assisting in
other ways.

Leo G. Abood, Ph.D., Department of Pharmacology, University of
Rochester Medical Center, Rochester, New York
John S. Baer, Ph.D., Department of Psychology, University of
Washington, Seattle, Washington
Timothy B. Baker, Ph.D., Department of Psychology, University of
Wisconsin, Madison, Wisconsin

Claudia R. Baquet, M.D., M.P.H., Chief, Special Populations Studies
Branch, Division of Cancer Prevention and Control, National
Cancer Institute, Bethesda, Maryland
Glen Bennett, M.P.H., Field Studies Advisor, Office of Prevention,
Education, and Control, National Heart, Lung, and Blood Insti-
tute, Bethesda, Maryland

George E. Bigelow, Ph.D., Associate Professor of Behavioral Biology,
Director, Behavioral Pharmacology Research Unit, Department of
Psychiatry and Behavioral Sciences, The Johns Hopkins Universi-
ty School of Medicine, Baltimore, Maryland
Clarice Brown, M.S., Data Analyst, Office of Prevention, Education,
and Control, National Heart, Lung, and Blood Institute, Bethesda,
Maryland

David M. Burns, M.D., Associate Professor of Medicine, Division of
Pulmonary and Critical Care Medicine, University of California
Medical Center, San Diego, California
Donald R. Cherek, Ph.D., Department of Psychiatry and Behavioral
Sciences, Mental Sciences Institute, The University of Texas
Health Science Center, Houston, Texas
Paul B.S. Clarke, Ph.D., Department of Pharmacology and Thera-
peutics, McGill University, Montreal, Quebec, Canada
Ro Nemeth-Coslett, Ph.D., Psychologist, Prevention Research
Branch, Division of Clinical Research, National Institute on Drug
Abuse, Rockville, Maryland

Thomas J. Crowley, M.D., University of Colorado Health Sciences
Center, Denver, Colorado

Joseph W. Cullen, Ph.D., Deputy Director, Division of Cancer
Prevention and Control, National Cancer Institute, Bethesda,
Maryland

K. Michael Cummings, Ph.D., M.P.H., Research Scientist, Depart-
ment of Cancer Control and Epidemiology, Roswell Park Memorial
Institute, Buffalo, New York

. .
x111


Susan Curry, Ph.D., Center for Health Studies, Group Health
Cooperative of Puget Sound, Seattle, Washington
Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland
Sir Richard Doll, University of Oxford, Oxford, England
Manning Feinleib, M.D., Dr.P.H., Director, National Center for
Health Statistics, Centers for Disease Control, Hyattsville, Mary-
land

William H. Foege, M.D., Executive Director, The Carter Center of
Emory University, Atlanta, Georgia
Richard R. Frecker, M.D., Ph.D., Head, Biomedical Research,
Department of Pharmacology, Addiction Research Foundation,
Toronto, Ontario, Canada

K.H. Ginzel, Ph.D., Professor, Department of Pharmacology and
Interdisciplinary Toxicology, University of Arkansas for Medical
Sciences, Little Rock, Arkansas
Russell E. Glasgow, Ph.D., Oregon Research Institute, Eugene,
Oregon

Nancy P. Gordon, Sc.D., Behavioral Scientist, Division of Research,
Kaiser Permanente Medical Group, Oakland, California
Roland R. Griffiths, The Johns Hopkins University School of
Medicine, Baltimore, Maryland

Ellen R. Gritz, Ph.D., Director, Division of Cancer Control, Jonsson
Comprehensive Cancer Center, University of California, Los
Angeles, California

Sharon M. Hall, Ph.D., Professor, Department of Psychiatry, Center
for Social and Behavioral Sciences, University of California, San
Francisco, California

Louis S. Harris, Ph.D., Senior Science Advisor, National Institute on
Drug Abuse, Alcohol, Drug Abuse, and Mental Health Administra-
tion, Rockville, Maryland

Ronald I. Herning, Ph.D., Addiction Research Center, National
Institute on Drug Abuse, Baltimore, Maryland
Dietrich Hoffmann, Ph.D., Associate Director, Naylor Dana Insti-
tute, Valhalla, New York

Leo Hollister, M.D., Medical Director, Harris County Psychiatry
Center, Houston, Texas

Enid Hunkeler, Senior Investigator, Kaiser Permanente Medical
Care Program, Oakland, California
Peyton Jacob III, Ph.D., Division of Clinical Pharmacology, San
Francisco General Hospital, University of California, San Francis-
co, California

Jerome Jaffe, M.D., Director, Addiction Research Center, National
Institute on Drug Abuse, Baltimore, Maryland
Murray E. Jarvik, M.D., Ph.D., The Neuropsychiatric Institute and
Hospital, School of Medicine, University of California, Los An-

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geles, and Veterans' Administration Medical Center West LOS
Angeles, Brentwood Division, Los Angeles, California
Martin Jarvis, M.Phil., Senior Lecturer, Addiction Research Unit,
Institute of Psychiatry, London, England
Chris-Ellen Johanson, Ph.D., Department of Psychiatry, Pritzker
School of Medicine, University of Chicago Drug Abuse Research
Center, Chicago, Illinois

Reese T. Jones, Ph.D., Department of Psychiatry, University of
California School of Medicine, San Francisco, California
Kenneth J. Kellar, Ph.D., Department of Pharmacology, Georgetown
University Medical Center, Washington, D.C.
Lynn T. Kozlowski, Ph.D., Head, Behavioral Research on Tobacco
Use, Addiction Research Foundation, Toronto, Ontario, Canada
Richard J. Lamb, Ph.D., Addiction Research Center, National
Institute on Drug Abuse, Baltimore, Maryland
Charles L. LeMaistre, M.D., President, University of Texas Systems
Cancer Center, Houston, Texas

Claude Lenfant, M.D., Director, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland
Howard Leventhal, Ph.D., Professor of Psychology, University of
Wisconsin, Madison, Wisconsin

Edward Lichtenstein, Ph.D., Oregon Research Institute, Eugene,
Oregon

Donald Ian Macdonald, M.D., Administrator, Alcohol, Drug Abuse,
and Mental Health Administration, Rockville, Maryland
G. Alan Marlatt, Ph.D., Professor of Psychology, University of
Washington, Seattle, Washington
William R. Martin, M.D., Chairman, Department of Pharmacology,
University of Kentucky College of Medicine, Lexington, Kentucky
James 0. Mason, M.D., Dr.P.H., Director, Centers for Disease
Control, Atlanta, Georgia

J. Michael McGinnis, M.D., Deputy Assistant Secretary (Disease
Prevention and Health Promotion), Washington, D.C.
A. Thomas McLellan, Ph.D., Substance Abuse Treatment Research
Center, Philadelphia Veterans' Administration Medical Center
and The University of Pennsylvania, Philadelphia, Pennsylvania
Nancy K. Mello, Ph.D., Alcohol and Drug Abuse Research Center,
McClean Hospital, Belmont, Massachusetts
Gregory J. Morosco, Ph.D., M.P.H., Smoking Education Program
Coordinator, National Heart, Lung, and Blood Institute, Bethesda,
Maryland

Joseph P. Mulholland, Ph.D., Bureau of Economics, Federal Trade
Commission, Washington, D.C.

Herbert W. Nickens, M.D., M.A., Director, Office of Minority Health,
Public Health Service, Washington, D.C.

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Richard Peto, M.A., M.Sc., Imperial Cancer Research Fund, Cancer
Studies Unit, Nuffield Department of Clinical Medicine, Radcliffe
Infirmary, University of Oxford, Oxford, England
Roy W. Pickens, Ph.D., Director, Division of Clinical Research,
National Institute on Drug Abuse, Rockville, Maryland
John P. Pierce, MSc., Ph.D., Chief, Epidemiology Branch, Office on
Smoking and Health, Center for Health Promotion and Education,
Centers for Disease Control, Rockville, Maryland
John M. Pinney, Executive Director, Institute for the Study of
Smoking Behavior and Policy, John F. Kennedy School of Govern-
ment, Harvard University, Cambridge, Massachusetts
Michael R. Polen, M.A., Research Associate, Division of Research,
Kaiser-Permanente Medical Group, Oakland, California
William Pollin, M.D., Former Director, National Institute on Drug
Abuse, Bethesda, Maryland

David C. Ramsey, M.P.H., Health Educator, Division of Health
Education, Center for Health Promotion and Education, Centers
for Disease Control, Atlanta, Georgia
Everett R. Rhoades, M.D., Assistant Surgeon General and Director,
Indian Health Service, Rockville, Maryland
M.A.H. Russell, F.R.C.P., Addiction Research Unit, Institute of
Psychiatry, University of London, London, England
Charles R. Schuster, Ph.D., Director, National Institute on Drug
Abuse, Rockville, Maryland

Burt Sharpe, M.D., Hennepin County Medical Center, Department of
Medicine, Minneapolis, Minnesota
Donald R. Shopland, Public Health Advisor, Smoking, Tobacco, and
Cancer Program, National Cancer Institute, Bethesda, Maryland
Jerome E. Singer, Ph.D., Medical Psychology, Uniformed Services
University of the Health Sciences, Bethesda, Maryland
Maxine L. Stitzer, Ph.D., Associate Professor, Behavioral Biology,
The Johns Hopkins School of Medicine, Behavioral Pharmacology
Research, Francis Scott Key Medical Center, Baltimore, Maryland
David N. Sundwall, M.D., Assistant Surgeon General and Adminis-
trator, Health Resources and Services Administration, Rockville,
Maryland

Dennis D. Tolsma, M.P.H., Director, Center for Health Promotion
and Education, Centers for Disease Control, Atlanta, Georgia
Frederick L. Trowbridge, M.D., Director, Division of Nutrition,
Center for Health Promotion and Education, Centers for Disease
Control, Atlanta, Georgia

Frank J. Vocci, Jr., Ph.D., Acting Chief, Drug Abuse Staff, Center for
Drug Evaluation and Research, Food and Drug Administration,
Washington, DC

Ronald W. Wilson, M.A., National Center for Health Statistics,
Centers for Disease Control, Hyattsville, Maryland

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Roy A. Wise, Ph.D., Department of Psychology, Concordia Universi-
ty, Montreal, Quebec, Canada
Faye Wright, Center for Applied Psychological Research, Depart-
ment of Psychology, Memphis State University, Memphis, Tennes-
see

Ernst L. Wynder, M.D., President, American Health Foundation,
New York, New York

James B. Wyngaarden, M.D., Director, National Institutes of Health,
Bethesda, Maryland

Tomoji Yanagita, M.D., Ph.D., Preclinical Research Laboratories,
Central Institute for Experimental Animals, Kawasaki, Japan
Frank E. Young, M.D., Commissioner, Food and Drug Administra-
tion, Rockville, Maryland

The editors also acknowledge the contributions of the following
staff members and others who assisted in the preparation of this
Report.

Margaret Anglin. Secretary, Office on Smoking and Health, Rock-
ville, Maryland

Charles Appiah, Project Clerk. Smoking and Health Project,. The
Circle, Inc., McLean, Virginia

John L. Bagrosky, Associate Director for Program Operations, Office
on Smoking and Health, Rockville, Maryland
Sonia Balakirsky, Secretary, Office on Smoking and Health, Rock-
ville, Maryland

Carol Bean, Associate Project Director, Smoking and Health Project,
The Circle, Inc., McLean, Virginia
Tamara Blair, Production Coordinator, Information Management
Department, ATLIS Federal Services, Inc., Rockville, Maryland
Catherine E. Burckhardt, Editorial Assistant, Office on Smoking and
Health, Rockville, Maryland

Gayle Christman, Word Processing Specialist, Smoking and Health
Project, The Circle, Inc., McLean, Virginia
Carol K. Cummings, Secretary, Office on Smoking and Health,
Rockville, Maryland

Stephanie D. DeVoe, Programmer, Information Systems Depart-
ment, ATLIS Federal Services, Inc., Rockville, Maryland
Michael C. Fiore, M.D., M.P.H., Medical Epidemiologist, Office on
Smoking and Health, Rockville, Maryland
David Fry, Editor, Smoking and Health Project, The Circle, Inc.,
McLean, Virginia

Lynn Funkhauser, Word Processing Specialist, Smoking and Health
Project, The Circle, Inc., McLean, Virginia
Mary Gardner, Senior Editor, Smoking and Health Project, The
Circle, Inc., McLean, Virginia

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Amy Garson, M.P.H. student, Office on Smoking and Health,
Rockville: Maryland

-4rnetta G. Glover, Secretary, Office on Smoking and Health,
Rockville, Maryland

William Groskopf, Library Acquisitions Specialist, Information
Management Department, ATLIS Federal Services, Inc., Rock-
ville, Maryland

Evridiki Hatziandreu, M.D., M.P.H., Epidemic Intelligence Service
Officer, Office on Smoking and Health, Rockville, Maryland
Susan A. Hawk, Ed.M., M.S., Chief, Technical Information Center,
Office on Smoking and Health, Rockville, Maryland
Patricia E. Healy, Technical Information Specialist, Office on
Smoking and Health, Rockville, Maryland
Terri L. Henry, Clerk-Typist, Office on Smoking and Health.
Rockville, Maryland

Timothy K. Hensley, Technical Publications Writer, Office on
Smoking and Health, Rockville, Maryland
Shirley K. Hickman, Data Entry Operator, Information Manage-
ment Department, ATLIS Federal Services, Inc., Rockville, Mary-
land

Robert S. Hutchings, Associate Director for Information and Pro-
gram Development, Office on Smoking and Health, Rockville,
Maryland

Karen Jacob, Senior Editor, Smoking and Health Project, The Circle,
Inc., McLean, Virginia

Sheila Jones, Word Processing Specialist, Smoking and Health
Project, The Circle, Inc., McLean, Virginia
Rick Keir, Senior Editor, Smoking and Health Project, The Circle,
Inc., McLean, Virginia

Julie Kurz, Graphics Specialist, Information Management Depart-
ment, ATLIS Federal Services, Inc., Rockville, Maryland
Diana Lord, Research Assistant, Department of Medical Psychology,
Uniformed Services University of the Health Sciences, Bethesda,
Maryland

Gerri E. Mast, Secretary, Center for Health Promotion and Educa-
tion, Centers for Disease Control, Atlanta, Georgia
Judy J. Mast, Secretary, Center for Health Promotion and Educa-
tion, Centers for Disease Control, Atlanta, Georgia
Dixie McGough, Program Manager, Information Management De-
partment, ATLIS Federal Services, Inc., Rockville, Maryland
Paul G. McGovern, Ph.D., Postdoctoral Research Associate, Smoking
Research Group, Department of Psychology, Iowa State Universi-
ty, Ames, Iowa

Dan McLaughlin, Editorial Assistant, Smoking and Health Project,
The Circle, Inc., McLean, Virginia

. . .
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Nancy Miltenberger, Editor. Smoking and Health Project, The
Circle, Inc., McLean, Virginia

Cathie O'Donnell, Senior Editor, Smoking and Health Project, The
Circle, Inc., McLean, Virginia

Ruth C. Palmer, Secretary, Office on Smoking and Health, Rockville,
Maryland

Russell D. Peek, Library Acquisitions Specialist, Information Man-
agement Department, ATLIS Federal Services, Inc., Rockville,
Mar.yland

Mary B. Pfeiffer, M.L.S., Librarian, Addiction Research Center,
National Institute on Drug Abuse, Baltimore, Maryland
Margaret E. Pickerel, Public Information and Publications Special-
ist, Office on Smoking and Health, Rockville, Maryland
Renate Phillips, Desktop Publishing/Graphic Artist, Smoking and
Health Project, The Circle, Inc., McLean, Virginia
Karen Sherman, Production Assistant, Information Management
Department, ATLIS Federal Services, Inc., Rockville, Maryland
Linda R. Spiegelman. Administrative Officer, Office on Smoking and
Health, Rockville, Maryland

Tamara Shipp, Publications Assistant, Smoking and Health Project,
The Circle, Inc., McLean, Virginia
Evelyn L. Swarr, Systems Management Projects Supervisor, Infor-
mation Systems Department, ATLIS Federal Services, Inc., Rock-
ville, Maryland

Patricia Y. Thomas, Secretary, Addiction Research Center, National
Institute on Drug Abuse, Baltimore, Maryland
Daniel R. Tisch, Project Director, Smoking and Health Project, The
Circle, Inc., McLean, Virginia

Louise G. Wiseman, Technical Information Specialist, Office on
Smoking and Health, Rockville, Maryland

xix


TABLE OF CONTENTS

Foreword ................................................................. i


Preface .................................................................. iii

Acknowledgments .................................................... ix

I. Introduction, Overview, Summary, and
  Conclusions . . . . . . . . . . . . . . . . . . ..**............................... 1

II. Nicotine: Pharmacokinetics, Metabolism, and Phar-
macodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

III. Nicotine: Sites and Mechanisms of Actions.. ........ .75


IV. Tobacco Use as Drug Dependence ..................... 145

V. Tobacco Use Compared to Other Drug
  Dependencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

VI. Effects of Nicotine That May Promote Tobacco
  Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377

$11. Treatment of Tobacco Dependence.. . . . . . . . . . . . . . . . . . . .459

Appendix A: Trends in Tobacco Use in the United
       States . . . . . , . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . .561

Appendix B: Toxicity of Nicotine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . 619

xxi