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TOBACCO, NICOTINE, AND ADDICTION r A Committee Report Prepared at the request of the ROYAL . SOCIETY OF CANADA for The Health Protection Branch Health and Welfare Canada

TOBACCO, NICOTINE, AND ADDICTION A Committee Report Prepared at the request of The Royal Society of Canada for The Health Protection Branch Health and Welfare Canada August 31, 1989

Canadian Cataloguing in Publication Data Main entry under title: Tobacco, nicotine, and addiction Text in English and French. Title on added t.p., inverted: Tabac, nicotine et toxicomanie. Includes bibliographical references. ISBN 0-920064-31-0 1. Tobacco habit-Canada. 2. Smoking-Canada. I. Royal Society of Canada. II. Canada. Health Protection Branch. III. Title: Tabac, nicotine et toxicomanie. HV5735.T62 1989 613.85 C90-090045-8E Other publications available from the Royal Society include: Corporate Plan 1989 $6.00 Plan for Advancement of Women in Scholarship $6.00 Plan for the Evaluation of Research in Canada $6.00 For information please contact: Royal Society of Canada P.O. Box 9734, Ottawa, Ontario K1G 5J4 O The Royal Society of Canada/La Societe royale du Canada, 1989 Graphic Design by Paradigm Documentation and Design Services Inc. $6.00 Printed in Canada by T&H Printers Limited

TABLE OF CONTENTS Page COMMITTEE MEMBERSHIP .................................................................................................... . iv SUMMARY .................................................................................................... .................................. V I. INTRODUCTION .................................................................................................... ................1 II. PAST AND CURRENT DEFINITIONS ................................................................................1 1. World Health Organization (WHO) Definitions .............................................................. 1 2. Other Clinical and Scientific Definitions ....... ................................•..........•••••-•••••......••••••3 3. Canadian Legal Definition ...............................................................................................5 4. Conclusion .................................................................................................... ...................... 6 III. BASIS FOR AN IMPROVED TERMINOLOGY .................................................................... 6 1. Factors Bearing on the Amount and Character of Drug Use .........................................6 2. Working Definition of Addiction ....................................................................................... 7 3. Dependence .................................................................................................... .................... 8 4. Habituation .................................................................................................... .................... 9 5. Addicting Drug or Addicted User? .................................................................................... 9 IV. EVIDENCE CONCERNING NICOTINE AND TOBACCO .................................................9 1. Introduction .................................................................................................... ................... 9 2. Repeated Use .................................................................................................... ...............10 3. Psychoactive Effects of Nicotine .....................................................................................12 4. Discriminative Stimulus and Subjective Properties .....................................................14 5. Reinforcing Effects of Nicotine . ......................................................................................15 6. Difficulty of Giving Up Smoking ......... ...........................................................................18 7. Other Forms of Tobacco Consumption ........................................................................... 22 V. CONCLUSIONS .................................................................................................... ................ 22 VI. REFERENCES .................................................................................................... .................. 23 VII. APPENDIX. POTENTIAL LEGAL AND SOCIAL IMPLICATIONS OF DESIGNATING NICOTINE AS ADDICTING ...................................................................29 Royal Society of Canada ul

. ... . . .."... ~ .............:.t..:•.....:..:. • COMMITTEE MEMBERSHIP The Royal Society of Canada, under contract from the Health Protection Branch, Health and Welfare Canada, requested the creation of a Committee to examine the relevant literature and advise the Department about the appropriate terminology for describing the type of dependence seen in cigarette smokers and users of other forms of tobacco. The Committee consisted of the following members: Dr. Paul B. S. Clarke Professor Martin L. Friedland Department of Pharmacology Faculty of Law Faculty of Medicine University of Toronto McGill University Toronto, Ontario Montreal, Quebec Professor Harold Kalant (Chairman) Dr. William A. Corrigall Department of Pharmacology Social and Biological Studies Division Faculty of Medicine Addiction Research Foundation University of Toronto Toronto, Ontario Toronto, Ontario Dr. Roberta G. Ferrence Dr. Lynn T. Kozlowski Social and Biological Studies Division Clinical Institute Addiction Research Foundation Addiction Research Foundation Toronto, Ontario Toronto, Ontario This membership provided coverage of the fields of behavioural pharmacology, clinical and experimental psychology, epidemiology, law, and neurophysiology. The Committee met in Toronto on June 28-29, August 3, August 18 and August 28,1989, to discuss background documents, agree on basic principles and concepts, and review drafts of the report at various stages in its preparation. In addition, there were frequent telephone consultations among Committee members between the meetings. Each member prepared an initial draft of one or more portions of the report, according to the individual areas of expertise, but the Committee as a whole was responsible for correcting all sections and integrating them into the final report. We are grateful to Ms. J. Shepperd, Mrs. V. Cabral, and Mr. J. Mihic for preparing and revising the manuscript in its numerous stages of evolution. iv Royal Society of Canada

SUMMARY This report was prepared in response to a specific question from the Health Protection Branch, Health and Welfare Canada: Which is the most appropriate term ["addiction", "de- pendence", or "habit formation"] to character- ize the risk of dependence on nicotine and, by extension, the use of tobacco products? To answer this question, a variety of defin- itions proposed by experts and expert committees in the past and present were reviewed and analysed critically, and a new definition of addiction was formulated before the specific case of tobacco was considered. The clinical and experimental evidence concerning nicotine and tobacco was then reviewed, with respect to each of the elements in the proposed definition. Earlier definitions of drug addiction have evolved over the past forty years, in the direction of diminishing emphasis on tolerance and phy- sical dependence as defining features of addiction, and growing emphasis on the be- havioural aspects of"compulsive" drug-seeking and drug-taking, reinforced by the psychoac- tive effects of the drug, and on the great diffi- culty in cessation of drug-taking and the high probability of relapse. The Committee proposes a further refinement of the definition by avoiding the imprecise and mechanistically questionable term "compul- sive", and separating the harmful long-term consequences of addiction from the process of addiction itself. The proposed def nition is: Drug addiction is a strongly estab- lished pattern of behaviour charac- terized by (1) the repeated self- administration of a drug in amounts which reliably produce reinforcin.g psychoactive effects, and (2) great dif f'icultyinachievingvoluntarylong- term cessation of such use, even when the user is strongly motivated to stop. The term dependence, as recommended by the World Health Organization, is potentially ambiguous unless further specified by the use of modifying terms that limit its general appli- cability to drugs of different pharmacological classes. The terms habit, habit formation, and habituation are even more ambiguous, vaguely defined, and scientifically ill-founded in relation to drug use, and should no longer be used in this context. The risk of addiction, in any individual drug user, is influenced by a number of factors, including genetic and psychological factors, route of drug administration, classical (Pavlovian) conditioning, cost, and a variety of other influences in the social environment. No drug that is generally regarded as addicting (e.g., heroin) gives rise to addiction in all, or even a majority, of those who experiment with its use. Therefore it is not necessary to prove that all tobacco users are addicted, in order to consider cigarette smoking as potentially addicting. Cigarette smoking can, and frequently does, meet all the criteria for the proposed definition of addiction: (i) It is used regularly (usually many times a day) by the majority of users, and most of those who experiment with cigarette smoking become regular dail) smokers. (ii) The amounts and patterns of use bN regular smokers are in most case: sufficient to maintain pharmacologicall; significant blood levels of nicotint throughout most of the day. (iii) Such nicotine levels have been showl to produce a variety of effects on th brain, altering chemical and electrc physiological aspects of brain functior and producing subjective effects thz the smoker recognizes, differentiatE Royal Society of Canada

from those of other drugs, and usually finds pleasurable. (iv) Sudden cessation of smoking gives rise to a withdrawal syndrome which can be alleviated by administration of nicotine. Other drugs that act on nicotine recep- tors in the brain also modify smoking patterns. (v) In experimental studies, both labora- tory animals and humans will expend considerable effort to self-inj ect nicotine intravenously in a manner similar to that shown in studies of heroin, cocaine, and other drugs that are generally regarded as addicting; i.e., the effects of nicotine are clearly reinforcing. (vi) Regular cigarette smokers have great difficulty giving up smoking, even when motivated to do so by the occurrence of respiratory, cardiovascular or other diseases caused or aggravated by smoking. Relapse rates among those who do stop smoking are high. The urge to smoke, among those who are also heavy users of alcohol or other drugs, is, in over 50% of cases, as strong as, or stronger than, the urge to use these other substances. (vii) Although much less evidence is avail- able concerning other forms of tobacco use, including cigars and pipes, snuffs, and chewing tobacco, they are capable of giving rise to plasma nicotine concen- trations as high as, or higher than, those achieved by cigarette smokers, though somewhat more slowly. The risk of addiction to these forms of tobacco use therefore warrants further study. The Committee therefore recommends that the patterns of cigarette use that meet the criteria set out above be regarded as nicotine addiction; that the term "dependence" be used only in specific senses indicated by appropriate modifying terms, rather than in a general sense identical to that of addiction; and that the terms "habit", "habit formation" and "habituation" not be employed at all in relation to the use of psychoactive substances. Certain legal and policy issues that would flow naturally from any official designation of tobacco and nicotine as addicting substances are considered in an Appendix to this report. Vi Royal Society of Canada

Tobacco, Nicotine, and Addiction I. INTRODUCTION The present inquiry was undertaken at the re- quest of the Health Protection Branch of Health and Welfare Canada, to answer a specif c question: Which is the most appropriate term ["addiction", "dependence", or "habit formation"] to characterize the risk of dependence on nicotine and, by exten- sion, the use of tobacco products? It is important to note that the purpose is not primarily to re-examine such issues as whether tobacco smoking is dangerous to the health of the smoker (or of those exposed involuntarily to the smoke), whether it is a very strongly entrenched behaviour that is often very diffi- cult to give up, whether many smokers persist in smoking despite personal desire or medical advice to stop or whether relapse is common among those smokers who do stop. All of these questions have been reviewed exhaustively in various reports by the U.S. Surgeon General (see, for example, U.S. DHHS 1988), and the answer to all ofthem is clearly in the affirmative. Rather, the purpose of this inquiry is to select the most appropriate term to designate or describe the attributes of tobacco smoking that are responsible for the strength and persist- ence of this behaviour, despite its well- demonstrated noxious consequences. This is not a trivial or insignificant purpose. The an- swer to the original question can have impor- tant implications for public policy, for the health care system, for preventive education programs, and possibly for the courts of law that may be called upon to assess responsibility for some of the untoward effects of smoking. Some of these implications are considered briefly in an Appendix to this report. If definitions were clear and universally ac- cepted, selection of the appropriate term would be a relatively simple matter. Unfortunately, there are still no universally adopted definitions of addiction, dependence or habituation, nor of their relationship to each other. The problem is illustrated by the circularity of the original question that led to this inquiry, viz., whether the risk of dependence on nicotine should be termed addiction, dependence or habit. Among the general public and the news media, cigarette smoking is widely regarded as an addiction. For example, in 1986 a Gallup Poll of Canadian adults, aged 18 and older, found that 77% of all respondents considered "ciga- rette smoking to be like a drug addiction," and 80% of current smokers felt they were addic- ted to cigarettes (Burson-Marsteller 1987). Unfortunately, neither the public nor the media usually define what they mean by addiction. In popular usage, it appears to mean anything from liking something enough to do it fre- quently, to being hopelessly enslaved by it. Therefore the term requires precise definition before it can be employed usefully in the law, in professional practice, and in education. The following sections of this report constitute an attempt to resolve the problem in a coher- ent and rational, though perhaps somewhat arbitrary, manner. First, the various defini- tions used by expert groups are reviewed with- out particular reference to any specific drugs. Next, the Committee sets out what it believes to be the soundest definitions consistent with both clinical experience and scientific theory. Then the key points of clinical and laboratory evidence are reviewed in relation to the ele- ments of these definitions. Finally, conclusions and recommendations are set out in response to the question posed by the Health Protection Branch. N II. PAST AND CURRENT a DEFINITIONS 1. World Health Organization (WHO) Definitions ~ ~ ~ m N tn w The most widely cited, though clearly not the most widely used, definitions in this field are those evolved by a succession of WHO Expert Committees and Working Groups over the past three to four decades. Up to 1964, the WHO Expert Committee on Drugs Liable to Produce Addiction endorsed separate definitions of drug addiction and habituation, of which the essen- tial features were as follows (WHO 1950): (a) Addiction was defined as a condition caused by repeated use of a drug, that Royal Society of Canada 1

Tobacco, Nicotine, and Addiction was characterized by a compulsive or overpowering need to seek and use the drug, physical dependence on it (as indi- cated by a characteristic withdrawal syndrome when the drug use was sud- denly stopped), tolerance (as indicated by a need to increase the dose to obtain the same degree of effect as that origi- nally produced by a smaller dose), and production of physical and/or functional damage both to the user and to society at large. (b) Habituation was thought to differ from addiction in that the user experienced a strong "desire" rather than a compulsive need to use the drug, use did not result in physical dependence, and damage (if any) was experienced only by the user and not by society at large. (c) Dependence was not seen as a separate entity, but as a component of addiction or habituation, and two types were dis- tinguished. Physical dependence, as defined above, was considered a cardinal feature of addiction and did not occur in habituation. Psychic (or "psychological") dependence was seen as a strong desire to take the drug, either to produce pleas- ure or to avoid discomfort (Kramer & Cameron 1975); it was not considered to be as serious or important as physical dependence, and could occur in habitu- ation as well as in addiction. A very important assumption in relation to these definitions was that the production of addiction or habituation depended entirely upon the pharmacological properties of the drug. Opiates, barbiturates and alcohol were regarded as addictive, while cocaine, amphetamines and tobacco (nicotine) were seen as habituating. No explicit roles were considered for individual susceptibility, route of administration, social context of use, or previous history of use of the same or other drugs. No attention was given to the fact that oral preparations of heroin (e.g., elixir of heroin and terpin hydrate) had been legally available as official pharmacopoeal preparations for many years, as medically esteemed antitussive remedies (cough suppres- sants), and had only rarely given rise to addic- tion, in contrast to the relative ease with which parenteral self-administration (i.e., by injec- tion) did so. Equally, no clear significance was attached to the fact that patients receiving parenteral opiates for relief of chronic pain frequently developed tolerance and physical dependence, yet failed to acquire compulsive drug-seeking and drug-taking behaviors that were considered characteristic of addiction. Conversely, no reference was made to the clini- cal observations that self-administration of cocaine could give rise to all the features re- garded as defining attributes ofaddiction (Maier 1926 [vide Kalant 1987]). These inconsistencies eventually became so troublesome that the WHO Expert Committee (which had changed its name to "Expert Com- mittee on Drug Dependence") recommended that the terms "addiction" and "habituation" be dropped altogether (WHO 1964). It recom- mended instead that they be replaced by the single term "dependence". This was defined as a state, psychic and sometimes also physical, resulting from the interac- tion between a living organism and a drug, characterized by behavioral and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects, and sometimes to avoid the discomfort of its absence. Tolerance may or may not be present. A person may be depend- ent on more than one drug. Recognizing that the relative order of impor- tance or prominence of these various compo- nents of "dependence" could differ in different cases, the WHO Committee further recom- mended that the term be followed by use of a drug-specific modifier, e.g., dependence of the opiate type, dependence of the alcohol type, dependence of the cocaine type, and so forth. This important conceptual change in the WHO definitions has several noteworthy implica- tions. First, it virtually eliminated the idea of different tiers of importance. By including in- travenous self-administration of heroin, oral consumption of alcohol, and pulmonary inha- lation of tobacco smoke under the single rubric of dependence, it made clear that the WHO Committee regarded all of these as potentially serious problems. Second, it no longer differen- tiated between damage to the user alone and damage to society at large. This change is N ~ 0 ~ -~ 41,, o• N cn ~ 2 Royal Society of Canada

Tobacco, Nicotine, and Addiction consistent with a social logic that recognizes that individual damage, such as tobacco-induced lung cancer, alcoholic cirrhosis of the liver, or cannabis-induced apathy and unemployment, carries social costs to the health care and welfare systems that are just as important as the more dramatic social costs, such as crime associated with heavy illicit use of opiates. Third, it gave clearly greater importance to psychic dependence than to physical depend- ence, thus recognizing the problem (whatever terminology was used) as primarily a behavi- oural rather than a physical one, though it could have important physical consequences. Fourth, it recognized the importance of the individual living organism that interacted with the drug, thus recognizing implicitly the exis- tence of individual differences in susceptibility to, and pattern of, drug dependence. dependence syndrome" was suggested as a single comprehensive designation that would include the motivational aspects of drug use (i.e., "psychic dependence"), as well as its con- sequences of "neuroadaptation" and possible damage. As pointed out by others (Brady & Lukas 1984), the proposed term "drug depend- ence syndrome" contains almost the same ele- ments as the older term "addiction", but had the two major advantages of differentiating clearly between the primary process (drug self- administration) and the secondary conse- quences, and of insisting on clinically and experimentally operational terms rather than value judgments based on undefined assumptions. 2. Other Clinical and Scientific Definitions Despite these major conceptual improvements, the 1964 WHO definitions still retained some features that are not in accord with present- day thought or practice. They continued to give much more emphasis to an assumed drug specificity than to common elements of the behavioural process. This is shown by the rec- ommendation to append the drug-specific phrase "of the (amphetamine, opiate, alcohol, etc.) type" to the generic term "dependence". They also made no mention of the route of drug administration, nor of the importance of social context of drug use in determining the pat- terns of use and the relative risk of dependence. A further refinement, proposed by a WHO Working Group rather than by the Expert Committee (WHO 1981), was designed to deal with the continuing ambiguity of the term "dependence", as well as with the problem posed by the widespread use of the undefined term "drug abuse". In a Memorandum on Nomenclature and Classifications drafted by the Working Group, it was proposed that the term "neuroadaptation" be used instead of "tolerance" and "physical dependence", since both of the latter phenomena were considered to reflect the adaptive changes that occurred in the central nervous system in response to repeated or prolonged exposure to the drug. It was further proposed that the term "abuse" be dropped altogether because it was essentially a value judgment term rather than an opera- tionally defined one. Instead, the term "drug Royal Society of Canada Despite the continued thought and effort, sus- tained over many years, that went into the refinement of the WHO definitions, these defi- nitions have not in fact been universally adopted and incorporated into every-day terminology. The term addiction continues to be widely employed, and is enshrined in the names of such well-known institutions as Ontario's Addiction Research Foundation (Canada), the Addiction Research Center of the National Institute on Drug Abuse (U.S.A.) and the Ad- diction Research Unit of the Institute of Psy- chiatry (U.K.), and of at least two major scien- tific journals in this field. It is therefore important to see how the term is defined in present-day usage, and what degree of concordance there is among the various definitions. No attempt will be made to review all the definitions to be found in the literature. It is sufficient for our purposes to examine a few that are representative of the majority of expert opinion and usage. 1VIDA-sponsored technical review The report of a technical review on cigarette smoking as an addiction (Krasnegor 1979), sponsored by the National Institute on Drug Abuse (NIDA), defined an addicting substance as "one that has: (1) pharmacological proper- ties leading to compulsive use; (2) a capability of producing organic and/or behavioral toxic- ity; and (3) a use pattern associated with adverse 2501446255 3