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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

Tobacco, Nicotine, and Addiction social consequences". It added that "this term is generally applied when the ingestion of such substances is viewed by a large segment of the society as undesirable". This definition suffers from several of the deficiencies noted above. As with the pre-1964 WHO definitions, it refers only to the substances and not to the users and the context. It establishes the consequences of the process (toxicity, adverse social effects) as defining criteria of the process itself. It appears to be directed principally toward illicit drugs or others "viewed by a large segment of the society as undesirable", thereby apparently omitting alcohol, which is approved and used by a large majority of the adult populations of most occi- dental countries. Nevertheless, this report does clearly indicate that compulsive use is the primary problem, and that physical dependence and tolerance, though important, are secondary. Diagnostic and Statistical Manual (DSM-III-R) The widely used Diagnostic and Statistical Manual (DSM-III-R) oftheAmerican Psychiatric Association (1987) employs a more flexible definition of "psychoactive substance de- pendence", which most North American psychiatrists now use interchangeably with "addiction". The defining criteria are given as at least three of: (1) substance often taken in larger amounts or over a longer period than the person intended (2) persistent desire or one or more unsuc- cessful efforts to cut down or control substance use (3) a great deal of time spent in activities necessary to get the substance (e.g., theft), taking the substance (e.g., chain smok- ing), or recovering from its effects (4) frequent intoxication or withdrawal symptoms [at times] when [the user is or should be] expected to fulfill major role obligations at work, school, or home (e.g., does not go to work because hung over, goes to school or work "hfgh", [is] intoxi- cated while taking care of his or her children), or when substance use is physi- cally hazardous (e.g., drives when intoxicated) (5) important social, occupational, or rec- reational activities given up or reduced because of substance use (6) continued substance use despite knowl- edge of having a persistent or recurrent social, psychological, or physical prob- lem that is caused or exacerbated by the use• oj' the substance (e.g., keeps using heroin despite family arguments about it, cocaine-induced depression, or hav- ing an ulcer made worse by drinking) (7) marked tolerance: need for markedly increased amounts of substance (i.e., at least a 50% increase) in order to achieve intoxication or desired effect, or mark- edly diminished effect with continued use of the same amount (8) characteristic withdrawal symptoms [specific for the different types of psy- choactive substance] (9) substance often taken to relieve or avoid withdrawal symptoms. This definition is unusual, in that the need for only three of the items listed above permits a diagnosis of dependence to be made on the basis of only compulsive or uncontrolled use (first six items) without reference to tolerance or physical dependence, or conversely on the basis of only tolerance and physical depend- ence (last three items) without reference to compulsive use or loss of control. It is also different from most other definitions in that untoward physical or social consequences are not defining criteria per se, but simply indices of the strength of the compulsion to continue using the substance despite knowledge of the adverse effect (item 6). Report of the U.S. Surgeon General (1988) A very important definition to be considered in the present context is that employed in the 1988 report of the U.S. Surgeon General (U.S. DHHS 1988) on the health consequences of smoking, in which nicotine is identified un- equivocally as addicting. Three primary crite- ria of addiction are stated: (1) drug-seeking and drug-taking behaviour is driven by strong, often irresistible, urges and can persist despite a desire to quit or even repeated attempts to quit; (2) the drug has psychoactive or mood- altering effects in the brain; (3) the drug is capable of functioning as a reinforcing agent that directly strengthens behaviour leading to further drug-taking. A number of other features 4 Royal Society of Canada

Tobacco, Nicotine, and Addiction are regarded as helping to delineate the pic- ture of fully established addiction, though not necessary for its definition. These include consistent and repetitive patterns of drug use, persistence of such use despite adverse conse- quences, frequent relapse, tolerance, physical dependence, persistent recurrent craving to use the drug (especially during periods of absti- nence), and effects that the user finds pleasur- able or euphoriant. Some of these defining or descriptive features seem repetitious or redundant. For example, persistence of use despite adverse consequences does not appear to differ from use driven by strong or irresistible urges. Pleasurable or euphoriant effects are, by definition, psychoac- tive or mood-altering effects, and are generally regarded as identical to, or closely related to, the postulated reinforcing effects. Neverthe- less, this definition/description, like the pre- ceding one in this section, gives primary em- phasis to the production and expression of drug-seeking and drug-taking behaviour, and only secondary importance to tolerance and physical dependence. Furthermore, adverse consequences are seen as important in their own right, but not as defining criteria of addic- tion; as in the DSM-III definition, they are used only as indices of the strength of the urge or need to continue using the drug. Dr. Jerome H. Jaffe A final definition to be considered here is that proposed by Dr. Jerome H. Jaffe, an interna- tionally recognized expert in the field of addictions, and author of the chapter on Drug Addiction and Drug Abuse in Goodman and Gilman's The Pharmacological Basis o f Thera- peutics (Jaffe 1985). In that chapter Dr. Jaffe has defined addiction as "a behavioral pattern of drug use, characterized by overwhelming involvement with the use of a drug (compulsive use), the securing of its supply, and a high tendency to relapse after withdrawal". This definition makes no reference whatever to the motivation for drug use, to tolerance and physi- cal dependence, or to the noxious consequences of drug use. Rather, it puts all the emphasis on the behavioural features of drug use, and uses the term in a purely descriptive rather than a mechanistic sense. This definition seems also to be directed principally toward use of illicit drugs such as heroin and cocaine, because of its inclusion of "the securing of its supply" as a defining characteristic. With licit substances such as alcohol that can be purchased easily, addiction does not usually involve any major preoccupation with the securing of a supply. 3. Canadian Legal Definition Canadian federal legislation already contains a definition of addiction. Section 2 of the Nar- cotic Control Act' offers the following defini- tion of a "narcotic addict": °`narcotic addict"means a person who, through the use of narcotics, (a) has developed a desire or need to continue to take a narcotic, or (b) has developed a psychological or physical dependence on the ef- fect of a narcotic. This is a very wide definition which, if the word "tobacco" were substituted for "narcotic", would virtually compel the conclusion that tobacco is addicting. This definition of "narcotic addict" must, however, be seen in the light of the special circumstances involved in its enactment in 19£1(Solomon and Green 1982, Le Dain 1973). A Special Committee of the Senate reported in 1955 on the `Traffic in Narcotic Drugs in Canada" and strongly recommended (p. xix) "the provision of suitable treatment facilities for drug addicts". Part II of the Narcotic Con- trol Act of 1961 responded to this recommenda- tion by requiring the sentencing j udge, if s atisfied "that the convicted person is a narcotic addict", to sentence the person "to custody for treat- ment for an indeterminate period". The 1955 Senate Committee had relied on the World Health Organization definition of addiction, current in the 1950s and discussed earlier in this document. The 1961 definition in the Narcotic Control Act was much broader. Part II of the Narcotic Control Act, however, has never been proclaimed in force - in part because of its draconian nature under the guise of treatment and in part its questionable con- stitutionality (Le Dain 1973, pp. 924 et seq.). 'Revised Statutes of Canada 1985, c. N-l. Royal Society of Canada 2501446257 5 • - - . _ _ . _ r-~n •~~,,.~.a~-+r•r . . . . . . . . . . . .. . . _ ... .. . . . . . : ~.7•.~.- . . . .. . . . . . . . ... . . . . . . . . . . . . . . . . . . . . ..

Tobacco, Nicotine, and Addiction Nevertheless, the definition of "narcotic addict" is still in force, but is only applicable to the unproclaimed Part II of the Act. Because of these special circumstances, little weight can be given to the only definition of "addict" now contained in federal legislation. 4. Conclusion The foregoing review of definitions of drug dependence or addiction indicates that these definitions have undergone a necessary and continuing evolution, as new clinical and ex- perimental information has been acquired. It is clear that, despite the differences among them, there are very important common elements. These are summarized as follows in the 1988 report of the U.S. Surgeon General: "According to current conceptualizations, the central and common element across all forms of drug dependence is that a psychoactive drug has come to control behavior to an extent that it is considered detrimental to the individual or society". However, the last portion of this summary appears to contradict the idea, implicit in both the D SM-III-R and the Surgeon General's definitions, that detrimental consequences are not defining criteria of addiction. Therefore the one uncontestable common element in pres- ent-day definitions is that "a psychoactive drug has come to control behavior". This single major element is the point of departure for our own definition, and for our subsequent assessment of its applicability to nicotine contained in tobacco products. III. BASIS FORAN IMPROVED TERMINOLOGY 1. Factors Bearing on the Amount and Character of Drug Use Drug use is not sharply divisible into "normal" and "abnormal" patterns, dr into "social use", "abuse", and "addiction". Abundant evidence shows that it falls on a continuum of amounts and frequencies, and is subject to a variety of factors to be considered below. It is desirable to review these factors before defining"addiction". Psychoactivity and reinforcement All known drugs that have at various times been considered "addicting", "dependence producing", or "habituating" are psychoactive drugs with demonstrated reinforcing proper- ties. In other words, they alter mood or perception in a manner that is regarded by most, but not all, users as pleasurable or desirable, and some aspect of this action reinforces (i.e., increases the likelihood of) renewed or repeated sel f-administration of such drugs. These reinforcing effects are not by themselves sufficient to produce dependence or addiction. Occasional, moderate users of such drugs usually experience qualitatively similar pleasurable and reinforcing effects. Yet these user's are not considered by most observ- ers to be dependent or addicted, because they are able to use or abstain at will, and the quantities they use are small. Therefore some additional factors must contribute to the pro- duction of addiction. Individual variables Individual factors may render some persons more sensitive than others to the reinforcing effects, or less sensitive to the disagreeable or punishing effects that may normally limit consumption of a drug. Such individual differ- ences may be of genetic or constitutional origin in some cases. The importance of genetic fac- tors has been studied in greatest depth in relation to susceptibility to alcohol addiction, but there is no a priori reason to doubt that it is also relevant to other drug addictions. There is evidence that sensitivity to many effects of nicotine in mice, and the ability to develop tolerance to these effects, are influenced by genetic factors (Collins et al. 1988). It is there- fore probable that genetic influences also mod- ify the reinforcing effects and the development of dependence. In other cases, differences in susceptibility may be due to emotional or physical discomfort that makes the same drug effects more highly valued by the user, e.g., anxiety or tension that may make the relaxant effects of alcohol, benzodiazepines or barbitu- rates more attractive to the user. In yet other cases, the social practices and values of the social group to which the user belongs may enhance the value of the drug effects by ena- bling the user's personality and behaviour to conform better to the group norms. For example, ~ 0 0 ~ .A ~ rQ cn 03 6 Royal Society of Canada

Tobacco, Nicotine, and Addiction a shy or inhibited person may find cocaine par- ticularly valuable if it permits easier accom- modation to a group of dynamic, extraverted, and aggressive friends or business associates. Route of administration The route of administration of the drug, by influencing the speed with which the reinforc- ing effects are perceived, can markedly influ- ence the strength of reinforcement. Intrave- nous or inhalational use of a psychoactive drug, which can deliver effective doses to the brain within seconds, is usually far more rein- forcing than oral ingestion of the same drug in the same or even larger doses (Kalant et al. 1978). Classical conditioning Frequently repeated use of the drug in a spe- cif c context (e.g., in a particular social setting, or during certain specific activities, or at par- ticular times of the day) can result in classical (Pavlovian) conditioning, so that the context itself comes to elicit the drug use or the desire for it (Wikler 1968). This is referred to as stimulus-controlled drug use (Kalant et al. 1978), and its appearance means that the drug use can no longer be regarded as a voluntary behaviour. Social and psychological environment Factors arising from the social and psychologi- cal environment also affect the degree of proba- bility that the foregoing factors may generate a pattern of compulsive use of a drug by a particular individual. For example, the great majority of those American troops in Viet Nam who became "addicted" to heroin during their military service in the Viet Nam war were quite successful in ceasing their use of heroin on their return to civilian life in the United States (Robins et al. 1977). It appears that the intense stress of war service, the low price and easy availability of heroin, widespread peer- group example and inducement to use the drug, and a high degree of'acceptance of the practice in the social milieu surrounding them, all contributed to the risk of use by individuals who did not use it in a different social context. Similarly, the cost of alcohol (in constant dol- lars) has been shown to have a marked effect on the level of consumption, even by drinkers Royal Society of Canada who are defined clinically as alcoholics (Babor 1985). When the price rises, consumption falls even among alcoholics, as shown by a corre- sponding fall in the incidence and death rate of alcoholic cirrhosis (Popham et al. 1976). The inverse relation between price and consump- tion has even been confirmed experimentally (Babor et al. 1978). This relationship probably applies to all drugs, as to most other commodi- ties. For example, the rapid increase in the use of "crack" (an impure preparation of the free base of cocaine) is generally attributed to the fact that its price is much lower than that of conventional preparations of cocaine. The rela- tionship has also been demonstrated with respect to tobacco. Russell (1973) found an inverse relationship between relative price and the average consumption of cigarettes among British men between 1946 and 1971; that is, as price rose, consumption fell, and as price fell, consumption rose. Research on smokers in the U.S. shows that a 10% increase in the price of cigarettes is associated with a 4% decrease in consumption among adults and a 14% de- crease among adolescents (Lewit et al 1981, Lewit and Coate 1982). Thus during periods when the relative price of cigarettes is declin- ing, we can expect corresponding increases in the percentage of smokers and the amount smoked. Factors such as these contribute importantly to the development of "compulsive" drug use. 2. Working Definition of Addiction Though North American experts increasingly regard dependence as identical with addiction, the continued broad acceptance of the term "addiction" (see Section 111.3), in both profes- sional and lay circles, makes it preferable to use the term "addiction" in the present report. As noted above, the dominant element in all the definitions reviewed is the presence of a strong, pervasive drug-taking behaviour that is very difficult to cease, even when damaging consequences of the drug use make the person wish to stop. All other features found in earlier definitions, including tolerance, physical de- pendence, and damage to health or social functioning, are consequences of the high levels of drug use generated by addiction, rather 7

Tobacco, Nicotine, and Addiction than essential features of it. They may contribute to or modify an existing addiction, but they are not essential criteria of addiction. There are numerous individual cases of heavy users of alcohol, opiates or other drugs who, because of protective features in their consti- tutions and environments, continue to func- tion at acceptable levels and suffer no obvious damage to health, but whose drug use is en- tirely comparable to that of clinically defined addicts. Therefore, we propose the following definition of drug addiction: Drug addiction is a strongly estab- lished pattern,of behaviour charac- terized by (1) the repeated sel f-ad- ministration of a drug in amounts which reliably produce reinforcing psycho-active effects, and (2) great difficulty in achieving voluntary long- term cessation of such use, even when the user is strongly motivated to stop. Notes: i) By "drug", we mean any substance other than a normal body constitueitt or one required for normal bodily function (e.g., food, water, oxygen) which, when ap- plied to or introduced into a living organ- ism, has the effect of altering bodily function. ii) By "repeated self-administration" we mean any pattern of continuous or inter- mittent drug-taking that includes periods of sustained intake at levels sufficient to produce reinforcing psychoactive effects. iii) By "reinforcing effects" we mean those that increase the probability of repeat- ing the behaviour (in this case, the drug- taking behaviour) that led to those effects. iv) By "psychoactive effects" we mean those drug effects resultingin changes in mood, perception and cognitive function, such as euphoria, tranquilization, hallucina- tions, arousal, improved endurance, etc. v) By "long-term cessation",we mean cessa- tion of the pattern of use described above, the cessation being maintained indefi- nitely over a period measured in years rather than in weeks or months. 3. Dependence As noted earlier, the WHO Expert Committee on Drug Dependence recommended that the term "addiction" be dropped from scientific and clinical use, and that it be replaced by the term "dependence". Though the term addic- tion continues to be widely employed, it has become increasingly common to use it inter- changeably with dependence. Indeed, this is done quite expressly in the Surgeon General's 1988 report on tobacco and addiction. We feel that the use of the term "dependence", without specific qualification, is ambiguous. In the 1964 report of the WHO Expert Committee, ambiguity was already evident in that depend- ence was defined in terms of both a psychic or behavioural component that was always pres- ent, and a physical component that might or might not be present. This is further compli- cated by the fact that a physical (physiological) dependence is clearly present in some indi- viduals with respect to drugs or substances that have nothing to do with drug addiction (e.g., the diabetic patient is physiologically dependent on insulin), but the definition does not differentiate between this type of physical dependence and the type identified by a with- drawal reaction in a chronic user of alcohol, heroin, or nicotine, for example. Moreover, it is widely recognized (e.g., Jaffe 1985) that someone can be made 'physically dependent on a drug by repeated medical administration of that drug (e.g., morphine administered to a patient by a nurse or physi- cian for relief of pain) in doses sufficient to produce a withdrawal reaction when the drug is stopped, yet show no subsequent opiate- seeking behaviour. Therefore physical depend- ence may be an accompaniment of addiction, but it may also occur in the absence of addic- tion, and addiction (as defined above) may occur in the absence of physical dependence. Therefore, there is a risk that use of the term "dependence" might be interpreted as imply- ing a different process than "addiction", or one of lesser magnitude or gravity. 8 Royal Society of Canada

Tobacco, Nicotine, and Addiction 4. Habituation As noted above, the term "habituation" was employed in earlier WHO Expert Committee reports to refer to a process that was consid- ered to be distinctly less serious than "addiction". This differentiation does indeed mirror popu- lar usage. In everyday speech, it is common to refer to something as "just a habit", to distin- guish it from something more serious that might be regarded as a problem, a dependence, or an addiction. In this sense, however, "habituation" to a psy- choactive drug is a vague term that can not be satisfactorily differentiated from regular, mod- erate "social" use. Moreover, it is not at all clear that, in terms of operant psychology, one can differentiate meaningfully between the proc- esses by which a behavior becomes established as a habit and those by which it acquires the features described above in relation to "addic- tion". It may be a matter of degree rather than of kind, and the point of differentiation is blurred. "Habituation" also has other technical mean- ings that are applicable to the use ofpsychoactive drugs. In experimental psychology it is used to designate the gradual loss of response to a sustained or regularly repeated stimulus. In relation to a drug it means the gradual loss of effect on repeated administration of the same dose, and thus is essentially the same as "tolerance". Therefore, we agree with the WHO recommendation (1964) that the term "habituation" no longer be employed in this context. In any event, once stimulus-controlled drug taking behaviour is present, "habituation" is no longer applicable. 5. Addicting Drug or Addicted User? Any drug that is used by some people in a "compulsive" and addicted manner can also be used by others in a voluntary and non-addicted manner. For example, over 85% of North American adults use alcohol, yet only 5-10% of drinkers use it in a manner which would be regarded clinically as alcoholism or alcohol addiction. Even heroin, which is regarded by many as the prototypic addicting drug, has been estimated to be used addictively by not more than 301/ . of those who try the drug (Robins et al. 1977). This is not surprising, given the importance ofandividual, social and environmental factors that modify the risk of addiction to any specific drug in a particular user. Nevertheless, it appears to be true that the proportions of addicted and non-addicted users vary not only in different populations and circumstances, but also with different drugs. Clinical, epidemiological and laboratory experience suggests that cocaine and heroin, for example, are likely to give rise to addiction in a higher percentage of users than alcohol or benzodiazepines are. In contrast, some other drugs (e.g., corticosteroids), which can occasionally give rise to euphoriant effects and addictive patterns of use, do so with such rarity that in those cases the users are considered ab- errant and the drugs themselves are not re- garded as addicting. Therefore, for nicotine in tobacco cigarettes to be considered an addicting drug, it is not neces- sary to prove that all users of it become ad- dicted, nor is it sufficient to show that in rare instances a user becomes addicted. Rather, it is necessary to show that the proportion of users who do become addicted is at least com- parable to that found among users of alcohol, opiates, or other drugs that are regarded virtu- ally universally as addicting. IV. EVIDENCE CONCER.NING NICOTINE AND TOBACCO 1. Introduction This portion of the report deals briefly with the major pieces of evidence bearing on each of the components of the definition of"addiction" given above, as they relate specifically to nicotine and to tobacco. These are: repeated use, psy- choactive effects, reinforcement, and difficulty of cessation. More detailed coverage of these and other topics can be found in the 1988 report ofthe U.S. Surgeon General (U.S. DHHS 1988). Only selected studies are summarized briefly here, together with more recent evidence Royal Society of Canada 9

Tobacco, Nicotine, and Addiction and some that relates specifically to Canadian experience. 2. Repeated Use Prevalence o f regular smoking There can be no doubt whatever that regular smoking of tobacco cigarettes is still widely prevalent in Canada. Of Canadians aged 15 and over, 33% smoke cigarettes, pipes or cigars at least occasionally and 28% smoke cigarettes regularly, usually every day (Figure 1). Among adolescents, aged 15-19, about 18% are "regu- lar" smokers. Rates of smoking in some groups are much higher. For example, more than half of young males (aged 20-44) with elementary school education are regular smokers (Millar 1988). Since smokers die sooner than non- smokers (U.S. DHHS 1989), smokers are un- derrepresented in older age groups. Amount of smoking by individual smokers Those who do smoke tend to smoke a lot. Of Canadian smokers aged 15 and over, 90% of those surveyed in 1986 reported that they usually smoked every day (Millar 1988). Of these "regular" smokers, 80% smoked more than 10 cigarettes per day. Only 10.6% of U.S. smokers smoked five or fewer cigarettes a day in 1985 (U.S. DHHS 1988, p.149). The average smoker uses 20-25 cigarettes a day (Kozlowski 1986). By comparison, only 23% of drinkers drink seven or more drinks per week (Statistics Canada 1987) and a much smaller proportion drink every day (Figure 2). Although average tar and nicotine levels have declined in recent years, 80% of smokers still smoke cigarettes with medium or high nicotine content (0.6-1.2 mg) (Millar 1988). Many smok- ers of low-nicotine cigarettes "get more" out of their cigarettes by puffing harder or blocking ventilation holes (Kozlowski et al. 1982), and a significant proportion of smokers (about 9% and increasing) smoke "roll-your-own" ciga- rettes, which are very high in nicotine and tar. Thus, few smokers actually take advantage of cigarettes with low tar and nicotine yields. In fact, Kozlowski (1989) has shown that very- low-yield cigarettes failed to capture a significant part of the market, even when heavily advertised. (The term "low-yield" can be used to cover both tar and nicotine, because they tend to move in parallel across the whole range of cigarette products.) Since significant blood levels of nicotine can be maintained with fewer than 10 cigarettes per day (see Section IV.3.a), this means that most smokers have pharmacologically significant levels of nico- tine in their bodies for most of the day. Studies of young people have yielded similar findings. Of students in grades 7-13 surveyed in Ontario in 1987, 24% reported smoking during the past year, about two-thirds of these smoked daily, and one-third smoked 6 or more cigarettes each day (Smart and Adlaf 1987). Of U. S. high school seniors surveyed in 1986, 30% had smoked at least once in the past 30 days. Of these, 65% smoked daily, 41% smoked at least half a pack a day, and 22% smoked a pack a day or more (Bachman et al. 1987). Experimentation and progression to regular smoking OfU.K. adults who had smoked at least once in their lives, 70% went on to smoke daily for five years or more (McKennell & Thomas 1967). Similarly, 75% of Irish adults who ever smoked at all, later became daily smokers for six months or more (O'Connor & Daly 1985). Among young people, 43% of high school seniors surveyed in the U.S. in 1987 who had tried one cigarette in their life had smoked at least once during the past 30 days; 29% had smoked daily and 18% had smoked one-half pack or more every day (Bachman et al. 1987). Among those who had tried 3 or more cigarettes, subsequent smoking was far more likely: 75% had smoked at least once during the previous 30 days; 48% had smoked daily; and 30% had smoked one-half pack or more. While few people begin smoking after high school, those who already smoke increase their daily intake once they graduate (Johnston et al. 1988). Summary Thus, it is clear that regular smoking of to- bacco cigarettes is still widespread in both Canada and the United States, among both adolescents and adults. The majority of those who experiment with smoking become regular daily smokers of substantial amounts, and 10 Royal Society of Canada

Tobacco, Nicotine, and Addiction FIGURE 1: SMOKING BEHAVIOUR OF CANADIANS BY AGE AND SEX,1988 (Labour Force Survey, 1986) ~ NEVER SMOKED O FORMER SMOKER ® REGULAR CIGARETTES ~ PIPE/C(GAR % Royal Society of Canada LV 'G' N KXA N I IX>V N AGE 11 ,..N... ., .. ~ .., ._ . . . ......... . ... .....

Tobacco, Nicotine, and Addiction FIGURE 2: DAILY CONSUMPTION OF ALCOLHOL AND CIGARETTES AMONG U.S. DRiNKERS AND REGULAR SMOKERS (National Health Interview Survey 1985) % 11-15 16-20 21-25 26-30 31-35 36-40 41+ NO. CIGARETTES/DRINKS PER DAY regularly smoke enough to sustain high blood levels of nicotine (see Section IV.3.2). 3. Psychoactive Effects of Nicotine This section consists of a review of evidence from a variety of sources suggesting that cig- arette smokers obtain nicotine in doses sufficient to act in the central nervous system (brain and spinal cord) and to produce psychoactive effects. While smokers attribute their smoking to a wide variety of motivating effects (McKennell 1970), most of these are consistent with the known psychopharmacological effects of nico- tine, which are discussed below. Plasma nicotine levels In abstinent subjects, the smoking of one ciga- rette elevates plasma nicotine levels by 12 approximately 10 ng/ml (Benowitz 1988), al- though this increase can vary markedly, de- pending on how the cigarette is smoked (U.S. DHHS 1988). Peak concentrations are attained as the cigarette is finished, and plasma levels then decline with a half-life of approximately two hours. In regular smokers, plasma nico- tine concentrations vary across the day-night cycle. In a group of heavy smokers (averaging 30 cigarettes per day), levels were lowest upon waking (approx. 5 ng/ml), rose within a few hours to a plateau (approx. 35 ng/ml), then declined through the night (Benowitz 1988). In view of the half-life of nicotine in humans and the high levels of nicotine attained by cigarette smokers, even 5-10 cigarettes a day are enough to ensure the maintenance of pharmacologi- cally significant blood levels of nicotine through- out the 24 hours of the day. Royal Society of Canada N cn 0 ~ ~ m N Q~ ~

Tobacco, Nicotine, and Addiction Nicotine levels in the human brain The concentration of nicotine in the central nervous system (CNS) of human subjects who smoke has not been measured. Theoretically this could be done by analyzing brain tissue ob- tained at autopsy from smokers who had died suddenly, shortly after smoking. Such studies do not appear to have been carried out. However, work done on experimental animals has shown that, after intravenous or intraperitoneal in- jection of nicotine, the concentration in the brain is approximately four times as high as that in venous blood plasma (Stalhandske and Slanina 1972, Mansner and Mattila 1977). If the same ratio applies to humans, as seems likely on the grounds of general similarity of drug distribution in the tissues of most species of mammals, a mean day-time nicotine concen- tration of 35 ng/ml in the plasma of smokers may correspond to a mean concentration of about 140 ng/ml (approximately 1 micromole per kg) in the brain. Effects of CNS levels of nicotine Studies in animals clearly demonstrate that at concentrations of around 1 micromolar, nico- tine exerts diverse actions within the central nervous system. These include enhanced re- lease of certain neurotransmitters (Giorguieff 1984) and increased electrophysiologic activity (Clarke 1990). When "smoking doses" of nicotine are admini- stered to laboratory animals, several psy- chopharmacological effects are seen which may help to explain why the drug is reinforcing (for reviews see Clarke 1987, U.S. DHHS 1988). For example, nicotine stimulates a variety of conditioned and unconditioned behaviours, and can alter the electroencephalogram (EEG) in a direction consistent with increased arousal; it can improve the performance of various tasks, particularly under stressful conditions; and it suppresses appetite for sweet foods. It is widely held among experts in the field of research on drug addiction that, for a drug to have the potential for giving rise to drug abuse and addiction, it must produce effects that are subjectively detectable by the user, and that produce "reinforcement" (as defined by operant behavioural principles). These topics are reviewed briefly below. In general, animal Royal Society of Canada studies provide evidence that nicotine per se plays an important role in cigarette smoking, irrespective of social factors which may modu- late.the behaviour in humans. Comparison of effects of cigarette smoke and nicotine When nicotine is injected in doses intended to reproduce concentrations encountered during cigarette smoking, it tends to mimic the effects of cigarette smoke. Examples include effects on the heart and blood vessels (Armitage et al. 1968), electrocortical desynchrony (Hall 1970, Domino 1973) as well as other changes in the electroencephalogram (Ashton et al. 1980), and increased release of the neurotransmitter dopamine from various sites in the brain (Fuxe et al. 1986). Reversal of smoking withdrawal symptoms by nicotine Cessation of smoking is attended by diverse withdrawal symptoms (see Table 2). The relative intensities of these symptoms vary from individual to individual, but certain symptoms are significantly correlated with pre-abstinence plasma nicotine levels (West and Russell 1985). In other words, the higher the mean plasma level of nicotine was before smoking was stopped, the greater are the probability and severity of tltese symptoms. The importance of nicotine in the maintenance of smoking is slfown by the ability of nicotine (delivered in polacrilex gum or by transdermal patch) to reverse many of the individual symp- toms that cons*:~t~ite, the tobacco withdrawal syndrome' (Ja:''t~is Ar'~2. 1982, Hughes et al. 1984, West et• al. 1984, Schneider et al. 1984, Abelin et al. 1989). Thus, the smoker who is physically dependent on nicotine continues to smoke, at least in part, to obtain enough nico- tine to prevent or treat nicotine withdrawal symptoms. This is consistent with the observa- tion that 58% of regular smokers smoke their first cigarette of the day within 30 minutes of waking (Burson-Marsteller 1987). Alteration of smoking behaviour by nicotine antagonists Most drugs produce their effects by combining with or binding to specific "receptors", i.e., specialized molecular structures on the surfaces 13 :~,.,~.~.~..r...y..... ,_.__.......___-__.---....

Tobacco, Nicotine, and Addiction of cells in the body, to which they are chemi- cally attracted. Certain other substances, chemically resembling the active drugs enough to bind to the same receptors, but lacking other molecular properties necessary for initiating the drug action, are called "antagonists" or "blockers" because they prevent drugs from activating the receptors, and thus block or antagonize the drug effects. There are a num- ber of nicotine antagonists, which block the binding of nicotine to its receptors in different parts of the body. For example, mecamyiamine blocks nicotine receptors both in the central nervous system and in the rest of the body (the "periphery"), whereas pentolinium blocks only the nicotine receptors in the periphery. In short-term studies of the effects of single doses of -such drugs ("acute studies"), mecamylamine increased several measures of smoking behaviour (Stolerman et al. 1973, Nemeth-Coslett et al. 1986) and nicotine in- take (Pomerleau et al. 1987), whereas pentolinium did not increase smoking behavi- our (Stolerman et al. 1973). The effects of mecamylamine were interpreted as reflecting a partial blockade of nicotinic receptors, in- creases in smoking being seen as an attempt to overcome the blockade. Given in sufficiently high doses in animals, mecamylamine appears to block many and perhaps all of the behavi- oural effects of nicotine (Clarke 1987); in particular, mecamylamine can block the rein- forcing effects of intravenous nicotine in ani- mals (see Section N.5). There is only one report to date of long-term ("chronic") use of nicotinic antagonists for the treatment of cigarette smoking (Tennant et al. 1983). This was a preliminary study lacking placebo controls. The subjects were all heavy smokers who used on average more than 40 cigarettes a day. Mecamylamine was given orally over a period of three weeks. Half of the subjects ceased smoking within eleven days. Subjective reports suggested that mecamy- lamine had blocked, the effects of nicotine. Although preliminary, this'study clearly sug- gests the importance of nicotine in maintain- ing smoking behaviour in long-term users. 4. Discriminative Stimulus and Subjective Properties As the above discussion demonstrates, nico- tine produces a variety of effects within the central nervous system. Of particular interest in the context of this report is the fact that, as a result of its central nervous system actions, nicotine, like other psychoactive drugs, pro- duces effects which can be discriminated by both humans and laboratory animals (Chance et al. 1977, Romano et al. 1981, Stolerman et al. 1984). In other words, nicotine produces subjective effects which enable the user (or the human or animal subject injected with nico- tine) to identify it and differentiate it from other drugs or from drug-free (placebo) solu- tions. These effects are referred to as the dis- criminative cue or discriminative stimulus properties of the drug. The ease of discriminat- ing a drug varies with the dose used; the minimum doses of nicotine that a laboratory rat can reliably discriminate produce plasma nicotine concentrations comparable to those found in human smokers (Pratt et al. 1983). Studies in anim.als have shown that the discriminative properties of drugs tend to be similar within similar pharmacological classes. That is, many drugs of the opiate class (such as morphine, heroin, or codeine) produce a dsasely similar dis .'*ninAtive cue in animals, whereas drugs of differing pharmacological types, such as opiates and psychomotor stimulants (e.g., cocaine and amphetamine), produce very dif- ferent discriminative cues in animals.l7iis is also generally true of the nicotine discrimina- -tive cue, although animals have been shown in discrimination tests to react to nicotine and the stimulant amphetamine in a way that indicates their subjective effects to be partially similar (Chance et al. 1977, Stolerman et aL 1984). Studies of the subjective effects of drugs in humans have permitted development and validation of a questionnaire that, among other measures, addresses whether a drug is liked by the subject. Research with human volun teers indicates that nicotine administered intravenously produces scores on the drug liking scale that increase with dose and that are similar in magnitude to scores obtained after administration of other substances 14 2501446266 Royad Society of Canada

Tobacco, Nicotine, and Addiction commonly regarded as drugs of abuse such as morphine and amphetamine (Jasinski et al. 1984). Another standard measure of a drug's subjec- tive effects was developed some years ago by the NIDA Addiction Research Center (ARC) in the United States. The ARC Inventory permits description of the subjective effects of a drug in terms of their similarity to the effects of other drug groupings. That is, a drug can be described as having effects similar to, or different from, those of the morphine-benzedrine group (MBG, drugs which produce feelings of euphoria or well-being), the pentobarbital-chlorpromazine- alcohol group (PCAG, drugs which produce sedation and intoxication), and the lysergic acid diethylamide group (LSD, drugs which produce dysphoria and fear). A study of volun- teer subjects who had histories ofboth smoking and non-medical use of other drugs found that the most prominent effects of intravenous nico- tine were increases in scores on both the MBG and LSD scales; the scores were dependent on the dose of nicotine administered to the sub- jects (Henningfield et al. 1985). These rating scores corresponded with subjective reports of a "rush" or "high" following nicotine admini- stration, but also of fear and discomfort pro- duced by the rapid and powerful drug effect. In this study, intravenous nicotine was identified as cocaine by six of the eight subjects and as amphetamine by one subject. Following inha- lation rather than intravenous injection of nicotine, similar but quantitatively smaller changes in scores on these drug scales were obtained. This evidence, and other data from similar studies discussed in greater detail in the Re- port of the U.S. Surgeon General (U.S. DHHS 1988), show clearly that nicotine, in the ab- sence of any of the other constituents of tobacco smoke and apart from the behaviour of smok- ing, is a psychoactive drug producing percep- tible effects, which are rated as "liked" and indeed even ranked as similar to effects pro- duced by other recognized "drugs of abuse". Royal Society of Canada 5. Reinforcing Effects of Nicotine Self-administration studies (i) Smoke inhalation patterns in humans Most smokers ensure that they derive a cen- tral nervous system effect from the nicotine in the cigarettes that they smoke. The average number of cigarettes smoked is 20 to 25 per day. Most smokers (92%) inhale, and most of these report that they draw the smoke into their chests (bronchi and lungs) and not just into their throats (Health and Welfare Canada 1981). This practice ensures rapid absorption of nicotine into the blood stream and rapid delivery to the central nervous system. Indirect evidence for the importance of the drug effect of nicotine is also provided by sales data. The distribution of tar and nicotine yields among smokers in the general population is roughly normal, with the largest proportion of smokers using medium-nicotine cigarettes (0.6- 0.9 mg). Average yield per cigarette has de- clined in the past decade, but appears to have levelled offin the medium range (Millar 1988). However, the direct test of whether or not a drug carries appreciable risk of giving rise to addiction consists of measuring whether an individual will repeatedly perform some task to obtain the drug. In behavioural pharmacol- ogical terms, this is called testing whether the drug maintains self-administration behaviour, and drugs that do so are said to be positive reinforcers because their self-administration ("presentation") maintains and strengthens ("reinforces") the behaviour leading to that presentation (Brady & Lukas 1984). (ii) Animal models of 25(? 1446267 sel f-administration To study drugs as reinforcers in experimental animals, the drug is usually administered through a catheter that has been surgically implanted in one of the subject's veins, al- though some drugs, such as ethanol, are made available to the animal for oral consumption in a small dipper or other device. In this report, we will focus on studies which use intravenous drug administration, since this most closely mimics the delivery of nicotine to the brain after inhalation ofcigarette smoke. In research 15 w~ .w.-. .--...+r.. - . . .. . -. . . . . . . . . . . . .

'['obacco, Nicotine, and Addiction of this kind, each subject is housed in a cham- ber equipped with response levers and a pump which can draw a drug solution from a reser- voir and pump it into the animal's catheter. The animal is free to move about the experi- mental chamber. The experimenter can vary the drug and its concentration in the solution, as well as the volume of solution that is infused in each single dose. To receive a drug infusion, the subject is required to press the lever ac- cording to some particular schedule, e.g., by making a certain number of presses for each drug injection. However, the animal is not forced to respond: pressing the lever is volun- tary. The test chambers in this research usually have two levers, but only one of these results in drug delivery to the animal when pressed; pressing on the other lever has no consequences. Control equipment, such as a computer sys- tem, monitors the responding on each lever, and initiates infusion of a small volume of drug solution from the pump each time the animal makes the required number and timing of responses on the drug-appropriate lever. Alarge number of scientific studies have shown that laboratory animals will press a lever re- peatedly to receive intravenous infusions of drugs, such as opiates and psychomotor stimu- lants, that are liable to be abused by humans (Schuster and Johanson 1974). In fact, this test is recognized as a valuable indication of the abuse liability of a drug because essen- tially allof the drugs that are abusedbyhumans are also self-administered by animals in such experiments, and agents that are not self- administered by animals are not usually abused by humans (Griffiths et al. 1980, Johanson and Schuster 1981). Studies of drug self- administration in animals also indicate the conditions under which a drug will be sought. For example, animals will administer cocaine to themselves over a wide range of conditions, whereas they take drugs such as ethanol and benzodiazepines in a more limited range of conditions. , With respect to nicotine, some studies have suggested that the conditions under which it supports self-administration are limited (e.g., Ator & Griffiths 1983, Henningfield and Gold- berg 1983a); this conclusion seemed to be par- ticularly warranted by the early attempts to establish self-administration of nicotine in rodents (e.g., Lang et al. 1977). However, most recent studies have shown that laboratory animals, of various species ranging from ro- dents to• primates, will work in a sustained fashion to receive repeated intravenous infu- sions of nicotine (see, for example, Corrigall & Coen 1989, Cox et al. 1984, Goldberg et al. 1981, Risner & Goldberg 1983, Spealman & Goldberg 1982). Indeed it is apparent from recent research with rodents that nicotine can generate substantial drug-taking behaviour over a range of doses (Corrigall & Coen 1989). In fact, it appears that nicotine self- administration can be demonstrated in a more straightforward way than can self-administra- tion of some other drugs with recognized addic- tive liability, such as alcohol (e.g., Beardsley et al. 1978). Data from the Corrigall & Coen (1989) study illustrate several aspects of nicotine self- administration (Figure 3). First, the amount of lever-pressing for intravenous infusions of nicotine depends upon the dose of the drug that is available, as is the case with other addictive agents. Second, when nicotine is no longer available, rates of lever-pressing behaviour decrease markedly to near-zero values. Third, although the animals can press either of two different levers, only one of which delivers nicotine, they respond almost exclusively on the lever that provides the drug to them. In this study, the animals were required to press the drug-appropriate lever 5 times for each infusion, and at doses of 0.01 and 0.03 mg/kg they took an average of approximately 15 infu- sions of nicotine in the one-hour experimental session, i.e., they pressed the lever at least 75 times. It is therefore evident that animals will work to receive intravenous infusions of nico- tine, an unequivocal demonstration of the re- inforcing effects of the drug. Like tobacco smolring by humans, intravenous nicotine self-administration in animals is al- tered by treatment with nicotine antagonists which act within the central nervous system, but not by those which act peripherally (e.g., Corrigall & Coen 1989, Risner & Goldberg 1983, Spealman & Goldberg 1982). This find- ing suggests that the drug-taking behaviour is due to the psychoactive effects of nicotine on the brain. 16 Royal Society of Canada

Tobacco, Nicotine, and Addiction FIGURE 3: NICOTINE SELF-ADMINiSTRATION y 120 W (n 100 W a 80-I 60-1, 40-I 20-I • Nicotine lever 0 Inactive lever Z 0 e <1 0.003 0.01 0.03 0.06 DOSE OF NiCOTtNE PER INFUSION (mg/kg) Two levers were available to the animals, only one of which delivered nicotine. To receive nicotine (via a permanently installed intrave- nous catheter), animals were required to press the appropriate lever five times for each infusion. Animals responded significantly only on the lever which resulted in the administration of nicotine to them (points marked by filled circles and labelled "nicotine lever" in this figure), and responded very little on the lever which administered nothing (open circles, labelled 5nactive lever"). Modified from Corr'rgaH and Coen (1989). (iii) Human self-injection studies Human studies have also examined whether nicotine can serve as a reinforcer when deliv- ered in isolation from the other constituents of tobacco smoke. Methodologically these experi- ments were conducted in a way similar to the studies of nicotine self-administration by ani- mals. Each subject had a catheter placed in a vein in his forearm, and had to press one of two levers 10 times in order to receive an infusion of nicotine. The subjects were not informed which lever delivered nicotine. Just as the experimental animals did, human subjects, presented with the opportunity to administer nicotine to themselves, engaged in this drug self-injection behaviour increasingly over time (Henningfield et al. 1983, Henningfield & Goldberg 1983b). In summary, studies with animals and hu- mans have shown that nicotine alone, apart from tobacco smoke, is self-administered un- der voluntary conditions in a way similar to the self-administration of known addictive drugs. Conditioned preference techniques (i) Place preference Although the intravenous self-administration technique is the experimental method that provides the most direct evidence of reinforc- ing effects of a drug, other experimental ap- proaches are also used in many laboratories. The two most widely employed such appro- aches are the conditioned place preference and conditioned taste preference techniques. The conditioned place preference method measures the amount of time that an animal voluntarily spends in an environment in which it has previously experienced the effects of a drug, and in a recognizably different environment in which it has experienced the "effects" of a placebo, when it is given free access to both environments simultaneously. The assump- tion is that if a drug has reinforcing effects, the animal will prefer the environment in which it experienced those effects, rather than the environment in which it received placebo. The method works well for some drugs that are voluntarily self-administered, such as mor- phine and cocaine (Mucha et al. 1982). How- ever, it works poorly with alcohol (Stewart and Grupp 1981, van der Kooy et al. 1983), despite Royal Society of Canada 2501446269 17

Tobacco, Nicotine, and Addiction the fact that alcohol is voluntarily consumed by experimental animals of various species as well as by humans, and is universally recog- nized as capable of giving rise to addiction in humans. (ii) Taste pre ference The conditioned taste preference technique is somewhat similar. The animal is allowed to taste a solution with a flavour that it has never experienced before (and that is neither very pleasant nor very disagreeable), shortly before it experiences the effects of a drug. In the ideal experimental design, it is also exposed to a different novel and equally acceptable flavour just before experiencing the "effects" of a pla- cebo. Subsequently, its voluntary intakes of the two flavoured solutions are compared in the absence of drug, when both solutions are freely available. Again, morphine and a num- ber of other opiates have been shown to gener- ate a preference for the flavour with which it had been paired (Mucha & Herz J985). How- ever, with other conditions and other doses, morphine, amphetamine, alcohol, and most other drugs that animals will self-administer tend to give rise to an aversion to (rather than a preference for) the flavour with which they have been paired (Cappell & LeBlanc 1975). (iii) Evidence about nicotine Therefore, the fact that nicotine gives incon- sistent results in place preference studies (Fudala et al. 1986, Clarke and Fibiger 1987, Carboni et al. 1989), and gives rise to a taste aversion rather than a taste preference (Kumar et al. 1983), can not be used as an aigument against the existence of reinforcing effects of nicotine. Rather, it reflects the fact that these procedures are sensitive to both reinforcing and punishing effects, including those of drugs which are capable of generating addiction. 6. Difficulty of Giving Up Smoking Quit-rates in the general population To assess whether use of a drug is difficult to give up voluntarily, it is critical to look at what proportion of individuals who try to give up actually succeed in giving up. In research on smoking cessation, one year of continuous abstinence from all tobacco products is used 18 typically as a measure of long-term success (Schwartz 1987). Most surveys, however, do not categorize for- mer smokers according to when they quit. Quit rates for Canadians surveyed in 1986 (per- centage of those who had ever smoked, who were now former smokers; Millar 1988) ranged from 31% for adolescents aged 15-19 to 70% of those aged 65 and over. While cessation does increase with age, the high quit rates among older Canadians are in part due to higher mortality among smokers who continued to smoke. Quit rates are also inflated because a significant proportion of those who listed them- selves as former smokers at the time of the survey subsequently returned to smoking. In Canada, 39% of current smokers surveyed in 1985 said they had tried to quit smoking during the past 12 months but had failed (Health and Welfare Canada, undated). A large, representative survey of smoking habits in the United States in 1986 (U.S. DHHS, 1989) found that: • 81% of those who had smoked at least 100 cigarettes in their lifetime had tried to quit smoking, • 64% of current smokers had tried to quit at least once, • 70% ofthose who had smoked in the past year had made at least one attempt to give up smoking at some point in their smoking career, • another 10% of those who had smoked in the past year said that "they had thought about it and would try to quit if there was an easy way to do so," • of those smokers who had tried to quit in the past year i) 18% quit for only 1-6 days and re- turned to regular smoking, ii) 35% quit for 7 or more days and were again current smokers, iii) thus, 53% (just over half) of those smokers who tried to quit in the past year had already failed to do so. Among those who have stopped smoking by the end of a smoking treatment program, as many as 75-$0~'o are likely to relapse to smoking in the next year (Hunt et al.1971). Nearly 40% of current smokers have failed to quit after Royal Society of Canada N) cn 0 ~ ~ .t~ m v 0 _ ..... .. . .,_~. .. , .. . . ~. . ...,.,.,.~,,.-, ~,,,,.,.

Tobacco, Nicotine, and Addiction three or more attempts (U.S. DHHS 1989). A survey in the United Kingdom (Marsh & Matheson 1983) showed that 70% of all current smokers have made at least one attempt to give up and half have made at least three attempts. because of the reliance on self-reports and inadequate consideration of early drop-outs from treatment. Further, there is no reason to expect a bias in the reports discussed by Schwartz that would under-estimate the quit- rates. As discussed earlier (Section 111.5), it would be unprecedented in the study of drug addiction to find a drug to which all regular users were addicted. Consequently, we do not expect that every smoker who tries to give up will have great difficulty in doing so. In the study by Marsh & Matheson, 19% of ex-smokers re- ported that they found giving up smoking"very difficult" and 27% found it "fairly difficult". The authors also noted that "The majority of triers who found it `impossible' have removed themselves from the count by resuming their habit." Marsh & Matheson also observed that "Those whose daily smoking intake fell into the 11-20 [cigarette] range found more diffi- culty [than lighter smokers], with 22% saying they found it `very difficult', and among those who gave up an even heavier habit this figure rises to 31%" (p. 31). As would be expected from the principles of addiction discussed in the earlier sections, signs of pharmacologically heavier tobacco use - in particular, starting smoking earlier in the day and smoking more cigarettes per day - are associated with greater difficulty in quitting (i.e., more inten- sive withdrawal effects) and lower probability of quitting (e.g., Heatherton et al. 1989, Pinto et al. 1987, Pomerleau et al. 1983). Quit rates in smokers who seek or are offered help in stopping Schwartz (1987) has recently reviewed the ef- fectiveness of smoking cessation methods in the United States and Canada. Table 1 is reproduced from his report. If we use the stan- dard of at least 1-year followup, it is striking that the median quit-rates range from 6% to 43%, with an average median quit-rate o€26%. (This average is calculated from the data in the Table and is used to provide a summary esti- mate of central tendency.) This clearly illus- trates that the large majority of smokers who are exposed to smoking cessation programs have either never stopped smoking at all or returned to smoking within one year. It should also be emphasized that many of the quit-rates considered by Schwartz are likely to be inflated Royal Society of Canada Unselected patients advised to stop by a physi- cian in general practice show a relatively low median quit-rate of only 6%. Evidence that even well-motivated groups show a low proba- bility of long-term quitting is one of the best indications that cigarette smoking is addic- tive. The highest quit-rates, not surprisingly, are found among smokers who are already patients with cardiac disease and hence highly motivated to stop smoking; but even among these patients, the median out of 16 studies shows that the majority (about 60%) do not stop smoking permanently. Nicotine withdrawal syndrome The nicotine withdrawal syndrome, as described in the DSM III-R, has been well established by research (see U.S. DHHS 1988, and Table 2). Though such a withdrawal syndrome may well be a factor in early relapse to smoking, it is un- likely to be the only cause of relapse, in either the short or long term (e.g., Cnmm;ngs et al. 1985). By two months after the cessation of smoking, the nicotine withdrawal syndrome is much reduced, if present at all, and yet relapse to smoking still is common after this period (e.g., Hunt et al. 1971). Quitting smoking for the young smoker U.S. High School seniors were asked whether or not they felt they should reduce or stop their use of any drugs they were using at the time of the inquiry (Bachman et al. 1987). A higher proportion of smokers (63%) felt their use of cigarettes was a source of problems than did users of any other drugs (e.g., alcohol, 40%; marijuana, 56%; tranquilizers, 41%; cocaine, 44%; heroin, 29%). More than half (53%) of half-pack-a-day smokers had tried to quit smoking and failed (Johnston et al. 1988). Al- most three-quarters of daily smokers continued to smoke every day 7 to 9 years later, even though only 5% of seniors had predicted that they would be smoking 5 years later. 2501446271 19

Tobacco, Nicotine, and Addiction TABLE 1 SUMMARY OF FOLLOWUP QUIT RATES OF 416 SMOKING CESSATION TRIALS BY METHOD Reported 1959-1985 At Least 1-Year Followup Intervention Method Number Range Median Percent 33% Self-Help 7 12-33 18 14 Educational 12 15-55 25 25 Five-Day Plan 14 16-40 26 21 Group* 31 5-71 28 39 Medication 12 6-50 18.5 17 Nicotine Chewing Gum 9 8-38 11 11 Nicotine Chewing Gum plus Behavioural Treatment or Therapy 11 12-49 29 36 Hypnosis - Individual 8 13-68 19.5 38 Hypnosis - Group 2 14-88 - 50 Acupuncture 6 8-32 27 0 Physician Advice or Counseling 12 3-13 6 0 Physician Intervention More Than Counseling 10 , 13-38 22.5 20 Physician Intervention Pulmonary Patients 6 25-76 31.5 50 Cardiac Patients 16 11-73 43 63 Risk Factor 7 12-46 31 43 Rapid Smoking 6 6-40 21 17 Rapid Smoking and Other Procedures 10 7-52 30.5 50 Satiation Smoking** 12 18-63 34.5 58 Regular-Paced Aversive Smoking** 3 20-39 26 33 Nicotine Fading** 16 7-46 25 44 Contingency Contracting** 4 14-38 27 25 Multiple Programs** 17 6-76 40 65 *Three group trials had 5-month followups. Other procedures may have been used, and some trials may be included in more than one method. Note: Percent 33% is percent of trials with quit rates of at least 33 percent. Median not calculated for less than three trials. These quit rates suggest overall trends only, since most were based on self-reports and some include patients who either did not com- plete treatment or failed to reply to followup inquiries. (Adapted from Schwartz ' 1987). 20 Royal Society of Canada N) tn 0 ~ ~ m ~ r,~

Tobacco, Nicotine, and Addiction TABLE 2 DIAGNOSTIC CATEGORIZATION AND CRITERIA FOR NICOTINE WITHDRAWAL Nicotine-induced organic mental disorder 292.00 Nicotine Withdrawal The essential feature of this disorder is a characteristic withdrawal syndrome due to the abrupt cessation of or reduction in the use of nicotine-containing substances (e.g., cigarettes, cigars, and pipes, chewing tobacco, or nicotine gum) that has been at least moderate in duration and amount. The syndrome includes craving for nicotine; irritability, frustration, or anger; difficulty concentrat- ing; restlessness; decreased heart rate; and increased appetite or weight gain. In many heavy cigarette smokers, changes in mood and performance that are related to withdrawal can be detected within 2 hours after the last tobacco use. The sense of craving appears to reach a peak within the first 24 hours after cessation of tobacco use, and gradually declines thereafter over a few days to several weeks. In any given case it is difficult to distinguish a withdrawal effect from the emergence of psychological traits that are suppressed, controlled, or altered by the effects of nicotine or from a behavioral reaction (e.g., frustration) to the loss of a reinforcer. Mild symptoms of withdrawal may occur after switching to low tar/nicotine cigarettes and after stopping the use of smokeless (chewing) tobacco or nicotine gum. Course. The symptoms begin within 24 hours of cessation of or reduction in nicotine use and usually decrease in intensity over a period of a few days to several weeks. Some former nicotine users report that craving for the substance continues for longer periods. Diagnostic Criteria for Nicotine Withdrawal A. Daily use of nicotine for at least several weeks. B. Abrupt cessation of nicotine use, or reduction in the amount of nicotine used, followed within 24 hours by at least four of the following signs: (1) craving for nicotine (2) irritability, frustration, or anger (3) anxiety (4) difficulty concentrating N CJ1 0 ~ ~ (5) restlessness A R7 (6) decreased heart rate (7) increased appetite or weight gain ~ w Condensed from the American Psychiatric Association's DSM-III-R (1987) Royal Society of Canada 21 +~~,.. . . , . . . . . ~.• ~-.. . .t.. ..~-~->. .. . ~..,. . _ .. ___. . ... . . . ..... . . .

0 on 4L 4.. T I Tobacco, Nicotine, and Addiction Comparison of cigarettes to known addictive drugs Recent research on the relative strength of self- reported urges to use drugs indicates that cigarette use involves relatively strong urges (Kozlowski et a1.1989). Individuals coming for treatment of alcohol and drug problems at a public hospital specializing in the treatment of such problems were asked to compare the "strongest urge" they had ever had for cigarettes and the "strongest urge" they had ever had for alcohol or the other drug for which they were seeking treatment. Among alcohol-dependent persons, 50% said their strongest cigarette urges were stronger than those for alcohol; 32% said that the urges were "about the same". Among drug-dependent persons, 25% said their strongest urges were for cigarettes and 27% said their strongest urges were "about the same". The majority (57%) of the drug and alcohol users also said that it would be harder to give up cigarettes than their "main" drug or alcohol. 7. Other Forms of Tobacco Consumption At the present time, smokeless tobacco is not widely used in Canada. About 1% of males aged 15 and over use chewing tobacco or "wet" or oral snuff, i.e., snuff that is placed between the cheek and gum or under the tongue (Millar 1987). Wh.ile no increase in use has occurred in Canada, substantial increases have been re- ported in the U.S. among adolescent males (U.S. DHHS 1989). The 1987 Ontario student survey found that 2.6% of males and 0.6% of females had used smokeless tobacco during the preceding four weeks (Smart & Adlaf 1987). Although the dose of nicotine and its rate of absorption vary from one method of admini- stration to another, snuffs, chewing tobacco, cigar and pipe smoke, and nicotine polacrilex gum all provide ways of taking the drug. From this point of view, inhalation of fine grain nasal snuff is closest to cigarette smoking, since com- parable plasma nicotine levels can be achieved rapidly (Russell et al. 1981). Inhaled pipe smoke, oral snuff, and chewing tobacco provide slower absorption of nicotine, but overall levels are similar to, or even higher than, those achieved by smoking cigarettes (Benowitz et al. 1988, 22 Ni a U.S. DHHS 1988). Nicotine polacrilex gum is associated with slow absorption and sustained levels of plasma nicotine one-third to two- thirds lower than those of habitual smokers (Benowitz 1988). The observation that even polacrilex gum, the least effective provider of nicotine, can affect the electrical activity of the brain cortex (Pickworth et al. 1988) and can ameliorate the symptoms of cigarette cessation (see above) argues strongly that all the forms of tobacco consumption mentioned above are able to provide nicotine in doses sufficient to produce psychoactive effects. There seems to be little information available concerning the ease with which these other forms of tobacco consumption can be given up. At least one study has indicated that interrup- tion of the use of chewing tobacco can give rise to a withdrawal syndrome essentially similar to that seen on cessation of cigarette smoking (Hughes et al. 1987). It has been hypothesized that cigarette smoking may be particularly intractable by virtue of the short t'ransit time for nicotine to pass from the lung to the brain, combined with the large number of occasions on which such actions are repeated in the life of an average smoker (Russell & Feyerabend 1978). This hypothesis implies that other forms of tobacco consumption may be less addictive than cigarette smoking. Nevertheless, the risk of addiction still appears to be appreciable. V. CONCLUSIONS . 1. A critical review of definitions formulated by a variety of experts and expert commit- tees in the field of drug abuse and drug dependence, and of evidence in the litera- ture, as well as the experience of the pres- ent Committee, leads us to adopt the fol- lowing definition of drug addiction: Drug addiction is a strongly es- tablished pattern of behaviour I Cn 0 ~ characterized by (1) the repeated ~ ~ self-administration of a drug in amounts which reliably produce reinforcing psychoactive effects; m rv v .~ Royal Society of Canada ..........-+.,.....-.-r ...>-...~.~.~.~.,.,-.~.~.-...,.~,-: ..«..,• -' i

Tobacco, Nicotine, and Addiction and (2) great difficulty in achiev- ing voluntary long-term cessation of such use, even when the user is strongly motivated to stop. 2. The term "drug dependence", although recommended by the World Health Organization, is potentially ambiguous and is not as satisfactory a term as "addiction" for general public and professional use. 3. The term "habituation" is unquestionably ambiguous and likely to be misunderstood, and should not be used at all in relation to the non-medical use of psychoactive drugs. 4. Cigarette smoking can, and frequently dQes, meet the criteria for the definition of drug addiction. When it does so, it should be de- scribed as nicotine addiction, because the clinical and experimental evidence supports the view that the addictive behaviour in such cases is generated and maintained by psychoactive and reinforcing effects of nicotine. 5. Evidence concerning other forms of tobacco use, including cigars, pipes, snuffs and chewing tobacco, is much less abundant than that concerning cigarette smoking, and is insufficient to support a firm conclu- sion about the risk of addiction to these forms of nicotine use. However, such infor- mation as there is available concerning the plasma levels of nicotine that can be pro- duced by the use of these alternative forms, and occasional clinical descriptions of pat- terns of use conforming to the definition given above, make it probable that addiction to non-cigarette forms of tobacco use can and sometimes does occur. The first, illustrated by the published writings of Warburton (1989), is that "compulsive use" and physical dependence in relation to smok- ing are trivial in comparison with heroin or cocaine; that psychoactive effects, including reinforcing effects, are not clearly demonstrable for nicotine; and that smoking has no deleteri- ous effects on the psyche of even the long-term smoker. The second, illustrated by a paper by Schwartz (1989), is that addictive behaviour is moti- vated primarily by conscious choice of the drug user, rather than by some compelling pharma- cological property of the drug. In this view, therefore, there is addictive behaviour but there are no addicting substances. We believe that the first argument is marred by errors of fact, but more importantly is largely irrelevant if addiction is defined as in Section 111. 2. The second argument has some merit, as we have recognized in Section 111.5, but it fails to give adequate recognition to the fact that the effects of a drug play a very important role in the user's "choice" to employ it again. Therefore, we believe that the great bulk of scientific information supports the conclusions of this Report. VI. REFERENCES Abelin, T.; Buehler, A.; Muller, P.; Vesanen K.; and Imhof, P.R. (1989). "Controlled trial of transdermal nicotine patch in tobacco withdrawal." Lancet I: 7-9. 6. Official recognition of the existence of nico- tine addiction could have a variety of legal and policy implications, some of which are reviewed briefly in the Appendix. Though the present Committee adopted these conclusions unanimously, it'recognizes that there is a small but significant body of scien- tific opinion which rejects the idea that nico- tine, or cigarette smoking, can give rise to addiction. Such dissenting views appear to be based on one or other of two different arguments. American Psychiatric Association (1987). Di- agnostic and Statistical Manual of 111ental Dis- orders, Edition III, revised. Armitage, A.K; Hall, G.H.; and Morrison, C.F. (1968). "Pharmacological basis for the smok- ing habit." Nature 217: 331-334. Ashton, H.; Marsh, V.R.; Millman, J.E.; Rawl- ins, M.D.; Telford, R.; and Thompson, J.W. (1980). "Biphasic dose-related responses of the CNV (contingent negative variation) to i.v. nicotine in man." British Journal of Clinical Pharmacology 10: 579- 589. Royal Society of Canada 23

Tobacco, Nicotine, and Addiction Ator, N.A. and Griffiths, R.R. (1983). "Nicotine self-administration in baboons." Pharmacol- ogy Biochemistry & Behavior 19: 993-1003. Babor, T.F. (1985). "Alcohol, economics and the ecological.fallacy: Toward an integration of experimental and quasi-experimental re- search." In Single, E. and Storm, T. (eds.) Public Drinking and Public Policy, Proceed- ings of a symposium on observation studies, Banff, Alberta, pp. 161-189. Toronto: Addic- tion Research Foundation. Babor, T.F.; Mendelson, J.H.; Greenberg, I.; and Kuehnle, J. (1978). " Experimental analy- sis of the "Happy Hour": effects of purchase price on alcohol consumption." Psychophar- macology 58: 35-41. Backman, J.G.; Johnston, L.D.; and O'Malley, P.M. (1987). Monitoring the future: Question- naire responses from the Nation's High School Seniors. Ann Arbor: University of Michigan. Beardsley, P.M.; Lemaire, G.A.; and Meisch, R.A. (1978). "Ethanol-reinforced behavior of rats with concurrent access to food and water." Psychopharmacology 59: 7-11. Ber_owitz, N.L. (1988). "Pharmacologic aspects of cigarette smoking and nicotine addiction." New England Jogrnal of Medicine 319: 1319-1330. Benowitz, N.L.; Porchet, H.; Scheiner, L.; and Jacob, P. (1988). "Nicotine absorption and card- iovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum." Clinical Pharmacology and Therapeutics 44: 23-28. Brady, J.V. and Lukas, S.E., eds., (1984). Test- ing Drugs for Physical Dependence Potential and Abuse Liability. Committee on Problems of Drug Dependence, Inc. NIDA Research Monograph 52. Rockville: National Institute on Drug Abuse. Burson-Marsteller (1987). Canadian attitudes towards nicotine addiction among smokers and ex-smokers. Prepared for Merrell-Dow Phar- maceuticals in collaboration with the Addic- tion Research Foundation and Canadian Coun- cil on Smoking and Health, January. 24 Cappell, H.D. and LeBlanc, A.E. (1975). "Conditioned aversion by psychoactive drugs: does it have significance for an understanding of drug dependence?" Addictive Behaviors 1: 55-64. Carboni, E.; Acquas, E.; Leone, P.; and Di Chiara, G. (1989). "5HT3 receptor antagonists block morphine- and nicotine- but not am- phetamine-induced reward." Psychopharma- cology 97: 175-178. Chance, W.T.; Murfin, D.; Krynock, G.M.; and Rosecrans, J.A. (1977). "A description of the nicotine stimulus and tests of its generaliza- tion to amphetamine." Psychopharmacology 55: 19-26. Clarke, P.B.S. (1987). "Nicotine and smoking: a perspective from animal studies." Psychopharmacology 92: 135-143. Clarke, P.B.S. (1990). "The central pharmacol- ogy of nicotine: electrophysiological ap- proaches." In Wonnacott, S.; Russell, M.A.H.; and Stolerman, I.P. (eds.): Nicotine Psychophar- macology: Molecular, Cellular and Behavioural Aspects, pp. 158-193. Oxford: Oxford Univer- sity Press. Clarke, P.B.S. and Fibiger, H.C. (1987). "Ap- parent absence of nicotine-induced conditioned place preference in rats." Psychopharmacol- ogy 92: 84-88. Collins, A.C.; Miner, L.L.; and Marks, M.J. (1988). "Genetic influences on acute responses to nicotine and nicotine tolerance in the mouse." Pharmacology Biochemistry & Behavior 30: 269-278. Corrigall, W.A. and Coen, KM. (1989). "Nico- tine maintains robust self-administration in rats on a limited-access schedule."Psychophar- macology 96: 29-35. Cox, B.M.; Goldstein, A.; and Nelson, W.T. (1984). "Nicotine self-administration in rats". British Journal of Pharmacology 83: 49-55. Cummings, K.M.; Jaen, C.R.; and Giovino, G. (1985). "Circumstances surrounding relapse in a group of recent ex-smokers." Preventive Medicine 14: 195-202. Royal Society of Canada

Tobacco, Nicotine, and Addiction Domino, E.F. (1973). "Neuropsychopharma- cology of nicotine and tobacco smoking." In Dunn, W.L. (ed.): Smoking Behavior: Motives and Incentives, pp. 5-32. New York: Winston/ Wiley. Fudala, P.J. and Iwamoto, E.T. (1986). "Fur- ther studies on nicotine-induced conditioned place preference in the rat." Pharmacology Biochemistry & Behavior 25: 1041-1049. Fuxe, K., Andersson, K.; Harfstrand, A.; and Agnati, L.F. (1986). "Increases in dopamine utilization in certain limbic dopamine termi- nal populations after a short period of inter- mittent exposure of male rats to cigarette smoke." Journal of Neural Transmission 67: 15-29. Giorguieff, M-F. (1984). "Presynaptic regula- tion of neurotransmitter release in the brain: facts and hypothesis." Neuroscience 12: 347- 375. Goldberg, S.R.; Spealman, R.D.; and Goldberg, D.M. (1981). "Persistent behavior at high rates maintained by intravenous self-administra- tion of nicotine." Science 214: 573-575. Griffiths, R.R.; Bigelow, G.E.; and Henning- field, J.E. (1980). "Similarities in animal and human drug-taking behavior." In Mello, N.K. (ed.): Advances in Substance Abuse, Vol. 1, pp. 1-90. Greenwich, CT: JAI Press. Hall, G.H. (1970). "Effects of nicotine and to- bacco smoke on electrical activity of cerebral cortex and olfactory bulb." British Journal of Pharmcology 38: 271-286. Health and Welfare Canada, Statistics Can- ada. Canada Health Survey. Ottawa. Supply and Services Canada, 1981. Heatherton, T.F.; Kowlowski, L.T.; Frecker, R.C.; Rickert, W.S.; and Robinson, J. (1989). "Using self-reported time to the first cigarette of the day and number of cigarettes per day to measure heaviness of smoking." British Jour- nal of Addiction 84: 791-800. Henningfield, J.E. and Goldberg, S.R. (1983a). "Nicotine as a reinforcer in human subjects and laboratory animals." Pharmacology Bio- chemistry & Behavior 19: 989-992. Henningfield, J.E. and Goldberg,•S.R. (1983b). "Control of behavior by intravenous injections of nicotine in human subjects." Pharmacology Biochemistry & Behavior 19: 1021-1026. Henningfield, J.E.; Miyasato, K.; and Jasinski, D.R. (1983). "Cigarette smokers self-admini- ster intravenous nicotine." Pharmacology Bio- chemistry & Behavior 19: 887-890. Henningfield, J.E.; Miyasato, K.; and Jasinski, D.R. (1985). "Abuse liability and pharmacody- namic characteristics of intravenous and in- haled nicotine." Journal of Pharmacology and Experimental Therapeutics 234: 1-12. Hughes, J.R.; Hatsukami, D.K.; Pickens, R.W.; Krahn, D.; Malin, S.; and Luknic, A. (1984). "Effect of nicotine on the tobacco withdrawal syndrome." Psychopharmacology 83: 82-87. Hunt, W.A.; Barnett, L.W.; and Branch, L.G. (1971). "Relapse rates in addiction programs." Journal of Clinical Psychology 27: 455-456. Jaffe, J.H. (1985). "Drug addiction and drug abuse." In Gilman, A.G.; Goodman, L.S.; Rall, T.W.; and Murad, F. (eds.): Goodman and Gil- man's The Pharmacological Basis of Thera- peutics, 7th edition, pp. 532-581. New York: Macmillan. Jarvis, M.J.; Raw, M.; Russell, M.A.H.; and Feyerabend, C. (1982). "Randomised controlled trial of nicotine chewing-gum." British Medi- cal Journal 285: 537-540. Jasinski, D.R; Johnson, R.E.; and Henning- field, J.E. (1984). "Abuse liability assessment in human subjects." Trends in Pharmacologi- cal Sciences 5: 196-200. Johanson, C.E. and Schuster, C.R. (1981). "Animal models of drug self-administration." In Mello, N.K. (ed.): Advances in Substance Abuse,Vol. 2, pp. 219-297. Greenwich, CT: JAI Press. 2501446277 Royal Society of Canada 25 ............ ..... .. .:• ..... ..:. ...... .. ... .. ........... _.... ......

Tobacca, Nicotine, and Addiction Johnston, L.D.; O'Malley, P.M.; and Bachman, J.G. (1988). Illicit drug use, smoking, and drinking by America's High School students, College students, and ' Young Adults. 1975- 1987. Rockville, MD: National Institute on Drug Abuse. Kalant, H.; Engel, J.A.; Goldberg, L.; Griffiths, R.R.; Jaffe, J.H.; Krasnegor, N.A.; Meilo, N.K.; Mendelson, J.H.; Thompson, T.; and Van Ree, J.M. (1978). "Behavioral Aspects of Addiction: Group Report." In Fishman, J. (ed.): The Bases of Addiction, pp. 468-469. Berlin: Dahlem Konferenzen. Kalant, O.J., ed., (1987). Maier's "Cocaine Ad- diction" (Der Kokainismus). Toronto: Addic- tion Research Foundation. Kozlowski, L.T.; Wilkinson, D.A.; Skinner, W.; Kent, C.; Franklin, T.; and Pope, M. (1989). "Comparing tobacco cigarette dependence with other drug dependencies: Greater or equal 'difficulty quitting' and 'urges to use', but less pleasure from cigarettes." Journal of theAmeri- can Medical Association 261: 898-901. Kozlowski, L.T. (1989): "Evidence for limits on the acceptability of lowest-tar cigarettes." American Journal of Public. Health 79: 198- 199. Kozlowski, L.T. (1986). "Pack size, reported cigarette smoking rates, and public health." American Journal of Public Health 76: 1337-1338. Kozlowski, L.T.; Rickert, W.S.; Pope, M.A.; Robinson, J.C.; and Frecker, R.C. (1982). "Estimating the yield to smokers of tar, nico- tine, and carbon monoxide from the "lowest- yield" ventilated filter-cigarettes." British Jour- nal of Addictions 77: 159-165. Kramer, J.F. and Cameron, D.C., eds., (1975). Manual on Drug Dependence. Geneva: World Health Organization. Krasnegor, N.A., ed., (1979). Cigarette Smok- ing as a Dependence Process. NIDA Research Monograph 23. Rockville: National Institute on Drug Abuse. 26 Kumar, R.; Pratt, J.A.; and Stolerman, I.P. (1983). "Characteristics of conditioned taste aversion produced by nicotine in rats." British Journal of Pharmacology 79: 245-253. Lang, W.J.; Latiff; A.A.; McQueen, A.; and Singer, G. (1977). "Self-administration of nico- tine with and without a food delivery sched- ule." Pharmacology Biochemistry & Behavior 7: 65-70. Le Dain, G. [ChairmanJ (1973). Final Report of the Commission of Inquiry into the Non-Medi- cal Use o f Drugs. Ottawa: Information Canada. Lewit, E.M. and Coate, D. (1982). "The poten- tial for using excise taxes to reduce smoking." Journal of Health Economics 1: 121-145. Lewit, E.M.; Coate, D.; and Grossman, M. (1981). "The effects of government regulation on teenage smoking." Journal of Law Econom- ics 24: 545-569. Mansner, R. and Mattila, M.J. (1977). "Phar- macokinetics of nicotine in adult and infant mice." Medical Biology 55: 317-324. Marsh, A. and Matheson, J. (1983). Smoking attitudes and behaviour. London: Her Maj- esty's Stationery Office. McKennell, A.C. (1970). "Smoking motivation factors."British Journal of Social and Clinical Psychology 9: 8-22. McKennell, A.C. and Thomas, R.K. (1967). Adults' and Adolescents' Smoking Habits and Attitudes. London: Government Social Survey, HMSO. Millar, W.J. (1987). The Use of Chewing To- bacco and Snuff in Canada, 1986. Ottawa: Health and Welfare Canada. Millar, W.J. (1988). The Smoking Behaviour of Canadians-1986. Ottawa: Health and Welfare Canada, Ministry of Supply and Services Canada. Royal Society of Canada .._._....~ . -.-......., .................-..~...,.,.,.,.~...,.-.....,~......,~..,.

Tobacco, Nicotine, and Addiction Mucha, R.F. and Herz, A. (1985). "Motiva- tional properties of kappa and muopioid recep- tor agonists studied with place and taste pref- erence conditioning." Psychopharmacology 86: 274-280. Mucha, R.F.; van der Kooy, D.; O'Shaugh- nessy, M.; and Bucenieks, P. (1982). "Drug re- inforcement studied by the use of place condi- tioning in the rat." Brain Research 243: 91- 105. Pratt, J.A.; Stolerman, I.P.; Garcha, H.S.; Giardini, V.; and Feyerabend, C. (1983). "Dis- criminative stimulus properties of nicotine: further evidence for mediation at a cholinergic receptor." Psychopharmacology 81: 54-60. Risner, M.E. and Goldberg, S.R. (1983). "A comparison of nicotine and cocaine self- administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion." Journal of Pharmacology and Ex- perimental Therapeutics 224: 319-326. Nemeth-Coslett, R.; Henningfield, J.R.; O'Keefe, M.K.; and Griffiths, R.R. (1986). "Effects of mecamylamine on human cigarette smoking and subjective ratings." Psychophar- macology 88: 420-425. O'Connor, J. and Daly, M. (1985). The Smok- ing Habit. Dublin: Gill and Macmillan. Pickworth, W.B.; Herning, R.I.; and Henning- field, J.E. (1988). "Mecamylamine reduces some EEG effects of nicotine chewing gum in hu- mans." Pharmacology Biochemistry & Behav- ior 30: 149-.153. Pinto, R.P.; Abrams, D.B.; Monti, P.M.; and Jacobus, S.L. (1987). "Nicotine dependence and likelihood of quitting smoking." Addictive Behaviors 12: 371-374. Pomerleau, C.S.; Pomerleau, O.F.; and Majchrzak, M.J. (1987). "Mecamylamine pre- treatment increases subsequent nicotine self- administration as indicated by changes in plasma nicotine level." Psychopharmacology 91: 391-393. Pomerleau, O.F.; Fertig, J.B.; and Shanahan, S.O. (1983). "Nicotine dependence in cigarette smoking: an empirically-based multivariate model." Pharmacology Biochemistry & Behav- ior 19: 291-299. Popham, R.E.; Schmidt, W.; and de Lint, J. (1976). "The effects of legal restraint on drink- ing." In Kissin, B. and Begleiter, H. (eds.): So- cial Aspects ofAlcoholism. The Biology ofAlco- holism, Vol. 4. pp. 5 79-625. New York: Plenum Press. Royal Society of Canada Robbins, L.N.; Helzer, J.E.; Hesselbrock, M.; and Wish, E (1977). "Vietnam veterans three years after Vietnam: How our study changed our view of heroin." Problems of Drug Depend- ence 1977, pp. 24-40. Romano, C.; Goldstein, A.; and Jewell, N.P. (1981). "Characterisation of the receptor medi- ating the nicotine discriminative stimulus." Psychopharmacology 74: 310-315. Russell, M.A.H. (1973). "Changes in cigarette price and consumption by men in Britain 1946- 1971: a preliminary analysis." British Journal of Preventive and Social Medicine 27: 1-7. Russell, M.A.H. and Feyerabend, C. (1978). "Cigarette smoking. a dependence on high- nicotine boli." Drug Metabolism Reviews 8: 29-57. Russell, M.A.H.; Jarvis, M.J.; Devitt, G.; and Feyerabend, C. (1981). "Nicotine intake by snuff users." British Medical Journal 283: 814-817. Schneider, N.G.; Jarvik, M.E.; and Forsythe, A.B. (1984). "Nicotine gum vs. placebo gum in the alleviation of withdrawal during smoking cessation." Addictive Behaviors 9: 149-156. Schuster, C.R and Johanson, C.E. (1974). "The use of animal models for the study of drug abuse." In Gibbins, R.J.; Israel, Y.; Kalant, H.; Popham, R.E.; Schmidt, W.; and Smart, R.G. (eds.): Research Advances in Alcohol and Drug Problems, Vol. 1, pp. 1-31. New York: Wiley. Schwartz, A. (1989). "Views of addiction and the duty to warn." Virginia Law Review 75: 509-560. 2501446279 27 k

Tobacco, Nicotine, and Addiction Schwartz, J.L. (1987). Review and evaluation of smoking cessation methods: The United States and Canada, 1978-1985. Washington, D.C.: Division of Cancer Prevention and Con- trol, National Cancer Institute. ' Smart, R.G. and Adlaf, E.M. (1987). Alcohol and Other Drug Use among Ontario Students in 1987, and Time Trends since 1977. Solomon, R. and Green, M. (1982). "The first century: The history of non-medical opiate use and control policies in Canada, 1870-1970." University of Western Ontario Law Review 20: 307-336. Spealman, R.D. and Goldberg, S.R. (1982). "Maintenance of schedule-controlled behavior by intravenous injection of nicotine in squirrel monkeys." Journal of Pharmacology and Ex- perimental Therapeutics 223: 402-408. Stalhandske, T. and Slanina, P. (1972). "Age- dependent changes in nicotine distribution in the brain of the mouse." Acta Pharmacologica et Toxicologica 31: 341-352. Statistics Canada (1987). Health and Social Support, 1985, General Social Survey Analy- sis Series, Catalogue No. 11-612-E, No.l. Ot- tawa: Minister of Supply and Services Canada. Stewart, R.B. and Grupp, L.A. (1981). "An in- vestigation of the interaction between the re- inforcing properties of food and ethanol using the place preference paradigm." Progress in Neuropsychopharmacology 5: 609-613. Stolerman, I.P.; Garcha, H.S.; Pratt, J.A.; and Kumar, R. (1984). "Role of training dose in dis- crimination of nicotine and related compounds by rats." Psychopharmacology 84: 413-419. Stolerman, I.P.; Goldfarb, T.; Fink, R.; and Jarvik, M.E. (1973). "Influencing cigarette smoking with nicotine antagonists." Psy- chopharmacology 28: 247-259. Tennant, F.S.; Tarver, A.L.; and Rawson, R.A. (1983). "Clinical evaluation of mecamylamine for withdrawal from nicotine dependence." Problems of Drug Dependence 1983, pp. 239-246. U.S. DHHS (1988). The Health Consequences of Smoking: Nicotine Addiction. A Report of the Surgeon General. Rockville, MD: U.S. De- partment of Health and Human Services. U.S. DHHS (1989). Reducing the Health Con- sequences of Smoking: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services. van der Kooy, D.; O'Shaughnessy, M.; Mucha, R.F.; and Kalant, H. (1983). "Motivational prop- erties of ethanol in naive rats as studied by place conditioning." Pharmacology Biochemis- try & Behavior 19: 441-445. Warburton, D.M. (1989). "Is nicotine use an addiction?" The Psychologist 4: 166-170. West, R.J.; Hajek, P.; and Belcher, M. (1984). "Which smokers report most relief from crav- ing when using nicotine chewing gum?" Psy- chopharmacology 89: 189-191. West, R.J. and Russell, M.A.H. (1985). "Pre- abstinence smoke intake and smoking motiva- tion as predictors of severity of cigarette with- drawal symptoms." Psychopharmacology 87: 334-336. WHO (1950). WHO Expert Committee on Drugs Liable to Produce Addiction: Report on the Sec- ond Session. WHd Technical Report Series No. 21. Geneva: World Health Orgnization. WHO (1964). WHO Expert Committee on Drug Dependence. Report on the Thirteenth Session. WHO Technical Report Series No. 273. Ge- neva: World Health Organization. WHO (1981). "Nomenclature and classifica- tion of drug- and alcohol-related problems: A WHO memorandum." Bulletin WHO 59: 225- 242. Wikler, A. (1968). "Interaction of physical de- pendence and classical and operant condition- ing in the genesis of relapse." In Wikler, A. (ed.): The Addictive States, pp. 280-287. Balti- more: Williams & Wilkins. ~ ~ cr Co 0 28 Royal Society of Canada

Tobacco, Nicotine, and Addiction VII. APPENDIX: POTENTIAL LEGAL AND SOCIAL IMPLICATIONS OF DESIGNATING NICOTINE AS ADDICTING A legislative statement that tobacco may be addicting would almost certainly increase the likelihood of a number of consequential effects in other areas of the law. These would follow naturally, and it is appropriate that they be considered. Some of these effects might come about in any case because of scientific inquir- ies such as the 1988 U.S. Surgeon-General's Report and, indeed, the present report. Those drafting any legislation and others respon- sible for policy formulation can, to some extent at least, anticipate these effects and take them into consideration. We have obviously not explored this subject in depth and simply set out here some ideas for fuller consideration by others. smoking is addicting would increase the likeli- hood that addicted smokers will be able to argue successfully that they are being dis- criminated against in services, accommoda- tion and employment. The various Human Rights Codes can antici- pate such results through prior legislation or change a finding by a board of inquiry through corrective legislation. It would be less easy, however, to overcome a finding of discrimina- tion under the Canadian Charter of Rights and Freedoms, a constitutional document. Section 15 of the Charter provides: 15. (1) Every individual is equal be- fore and under the law and has the right to the equal protection and equal benefit of the law without discrimina- tion and, in particular, without dis- crimination based on race, national or ethnic origin, colour, religion, sex, age or mental or physical disability. The designation of tobacco as addicting would increase the likelihood that smokers will be able to bring complaints of discrimination under the various Human Rights statutes. The Fed- eral Act and all of the Provincial Acts now prohibit discrimination on the basis of what are referred to in some statutes as a "physical disability", in others as a "physical handicap", and in still others as a "physical characteris- tic"'. The Canadian Human Rights Act2, for example, uses the phrase "disability" which is defined as "any previous or existing mental or physical disability and includes disfigurement and previous or existing dependence on alcohol or a drug". The Ontario Human Rights Code3 prohibits discrimination in services, accommo- dation and employment "because of handicap". This is defined4 to include "any degree of physi- cal disability...that is caused by... illness". Smokers may have some difficulty coming within these definitions and, moreover, even if they do, the discrimination may be acceptable on the basis that it is a bona fide qualification under the legislation (for example, the prob- lems of second-hand smoke can in most cases justify smoke-free areas in restaurants, ac- commodation, and workplaces). Still, it seems obvious that a legislative declaration that Will tobacco addiction be considered a "mental or physical disability" under the Charter? Even if the answer is "yes", would legislation dis- criminating against smokers or smoking be upheld under section 1 which provides that the Charter "guarantees the rights and freedoms set out in it subject only to such reasonable limits prescribed by law as can be demonstra- bly justified in a free and democratic society"? We are not aware of any reported cases under section 15 involving alcohol or drugs, let alone tobacco. Iflitigation under other sections of the Charter is any guide, however, such cases can be expected in the future. There are now many cases and rulings involv- ing alcoholism and drug abuse in the workplace5. To the extent that it can be said that smoking is addicting, these cases and rulings may also be applicable to smokers. Labour arbitrators have held, to give one example, that under a collective agreement an employee is entitled to sick pay while undergoing treatment for alco- holism6. The same result may follow for an employee who seeks help in stopping smoking. We can also expect more claims for treatment costs against provincial health plans, private supplementary health schemes, and disability Royal Society of Canada 29

• Tobacco, Nicotine, and Addiction insurance plans if smoking is considered an addiction. Again, we are not making a judg- ment on whether these claims would be desir- able or not, but simply wish to alert policy makers to the possible consequences of desig- nating smoking as an addiction. A designation of addiction may have an effect on civil actions against cigarette manufactur- ers and distributors. On the one hand, it is likely to increase the chance of a plaintiff's success because of the lack of warning of addic- tion up until now'. On the other, it may de- crease the chance of success in a lawsuit for a person who commenced smoking after being adequately warned or if federal labelling legis- lation is held to preempt civil actions. The issue of preemption is not yet clear in U.S. law. Some American courts have held that federal label- ling legislation bars state civil actions because federal legislation is said to preempt state law". Other American courts, however, have held otherwise". Our federal Tobacco Products Control Act of 198810 specifically deals with the consequence of labelling by providing in section 9(3) that "This section does not affect any obligation of distributors, at common law or under any Act of Parliament or of a provin- cial legislature, to warn purchasers of tobacco products of the health effects of those prod- ucts". We assume that this section will be made to cover any labelling requirement with respect to addiction. Finally, if tobacco were to be designated as an addictive substance there would probably be a general expectation that careful control would be exercised over the distribution of tobacco products, and that minors in particular would have more difficulty in obtaining cigarettes than they do at present. I i 1See generally, W.S. Tarnopolsky, Discrimination and the Law in Canada, 2nd ed. (Toronto, De Boo, 1985) at 9-15 et seq. The Quebec Act refers to a "handicapped person" which is defined as "a person limited in the performance of normal activities who is suffering, significantly and permanently, from a physical or mental deficiency, or who regularly uses...means of palliating his handicap". ' 2Revised Statutes Canada 1985, c. H-6, s.25. 3Stat. Ont. 1981, c.53, ss.1, 2 & 4. 4s.9(b). 5See, e.g.,.W.F. Scanlon, Alcoholism and Drug Abuse in the Workplace: Employee Assistance Programs (New York: Praeger, 1986); J.M. Walsh and S.C. Yohay, Drug and Alcohol Abuse in the Workplace: A Guide to the Issues (Washington, National Foundation for the Study of Equal Employment Policy, 1987). 6See, e.g., Re American Can Co. of Canada and United States Steelworkers, Local 2821 (1981) 3 L.A.C. (3d) 283 (B.C.). See generally, D.J.M. Brown and D.M. Beatty, Canadian Labour Arbitration, 3rd ed. (Aurora: Canada Law Book, 1988), 8: 3320. 7See A. Schwartz, "Views of Addiction and the Duty to Warn" (1989) 75 Virginia Law Review 509 at pp. 510-511: "the chance for success was improved by the recent Surgeon General's report concluding that smoking is addictive, particularly since the report recommends that the tobacco companies be required to warn". 8See, e.g., Cipollone v. Liggett Group, Inc. (1986) 789 F. 2d 181 (3rd Cir.) 9See, e.g., Palmer v. Liggett Group, Inc. (1986) 633 F. Suppl. 1171 (D. Mass.), reversed (1987) 825 F. 2d 620 (1st Cir.) 1oStat. Can. 1988, c.20.