62 Tobacco Control 2001;10:62–64 Tob Control: first published as 10.1136/tc.10.1.62 on 1 March 2001. Downloaded from COMMENTARY

Why does smoking so often produce dependence? A somewhat diVerent view

John R Hughes

Abstract These explanations often give little emphasis The usual explanation for why smoking to the possibility that nicotine induces depend- produces dependence focuses on the ence because it produces beneficial eVects that eVects of nicotine on dopamine and other can help smokers cope with their environ- neurobiological explanations. This review ment.89 By beneficial eVects, I mean positive oVers four somewhat diVerent explana- eVects that are not due to relief of withdrawal tions: (1) nicotine can oVer several but rather are eVects above and beyond a “nor- psychopharmacological benefits at the age mal” baseline functioning.10 when such benefits are especially needed; Whether nicotine via smoking causes true (2) cigarettes provide for a rapid, beneficial eVects is, to many, debatable.891112 frequent, reliable and easy-to-obtain My belief (and that of others before me89) that reward; (3) nicotine is not intoxicating, nicotine can cause true beneficial eVects is allowing chronic intake; and (4) the long based on three sets of data. First, nicotine often duration of the nicotine withdrawal causes improvements in animals with no syndrome eVectively undermines cessa- history of nicotine exposure, in never smokers, tion. This article reviews the evidence for and in non-deprived smokers.8911 Second, the above views and the tobacco control most other drugs of dependence produce ben- activities these views suggest. eficial eVects—for example, cocaine produces (Tobacco Control 2001;10:62–64) stimulation and alcohol produces relaxation http://tobaccocontrol.bmj.com/ Keywords: nicotine; substance use disorder; substance and increased confidence. Third, the two other withdrawal; tobacco use disorder major explanations for nicotine dependence (euphoria and withdrawal relief) have Many of us are asked by fellow scientists, problems explaining the persistence of administrators, clinicians, acquaintances, and smoking. Euphoria is endorsed only 10% of tobacco lawyers why we think cigarette the time while smoking13 plus very few smokers smoking produces dependence. The usual report euphoria as a reason for smoking.14 response often emphasises brain changes, Withdrawal is often reported by adolescents7; genetics and other neurobiological explana- however, 77% of adolescents deny ever using tions as described in the 1988 surgeon cigarettes to avoid withdrawal symptoms.15 I general’s report.1 The present article proposes am not denying euphoria or withdrawal occur; four other factors that I and others believe are however, I believe they cannot adequately on September 24, 2021 by guest. Protected copyright. as important, to understanding nicotine explain the persistence of smoking. dependence (in this paper “dependence” refers Nicotine’s beneficial eVects are probably to the Diagnostic and statistical manual of mental especially potent in the transition from experi- disorders, fourth edition (DSM-IV) definition2). mental to regular smoking. Nicotine can My views are not new; however, I believe they produce several diverse eVects—that is, it can are much under appreciated both by tobacco reduce aggression, improve focus on cognitive control advocates and by biological scientists. tasks, increase vigilance, decrease weight gain, Plus, I believe they suggest concrete changes in and improve mood.16 These beneficial eVects Department of our tobacco control activities. are probably especially appealing to teenagers. Psychiatry, University Consider the issues most teenagers are dealing of Vermont, with. Many are trying to control their Burlington, Vermont, USA Nicotine, the “renaissance drug” aggression, to focus attention for long periods J R Hughes A common explanation of why nicotine and of time, to control their weight or to control other drugs can be dependence producing their mood.6 Typically, they have trouble mas- Correspondence to: John R Hughes MD, focuses on how drugs increase dopamine and tering these skills. When adolescents Department of Psychiatry, act on “reward centres” of the brain.1 3–5 Some- experiment with cigarettes, they may find that University of Vermont, 38 Fletcher Place, Burlington, times these explanations emphasise positive nicotine can help with some of these problems, VT 05401–1419, USA reinforcement (that is, pleasurable eVects often plus it is likely to be a more reliable solution john.hughes.uvm.edu termed euphoria) as the main cause of than their own fledgling skills. Although we 1 3–5 Received 26 May 2000 and dependence. Other times they emphasise have no direct tests of beneficial eVects of nico- in revised form 1 October 2000. Accepted 12 negative reinforcement—that is, smokers use tine in adolescents, it does seem likely that October 2000 cigarettes mostly to avoid withdrawal.367 many adolescents come to use cigarettes as a

www.tobaccocontrol.com Why smoking induces dependence 63 Tob Control: first published as 10.1136/tc.10.1.62 on 1 March 2001. Downloaded from multipurpose pharmacological coping strategy. Duration of nicotine withdrawal Whether this use of cigarettes for beneficial To many lay persons, a severe withdrawal syn- eVects persists and maintains smoking into drome which produces physical changes is a adulthood or whether the motive for smoking central characteristic of a drug dependence. changes to withdrawal relief is still unclear. Although nicotine withdrawal can be severe in some smokers, in most smokers it is not.23 24 I Rapid, frequent, reliable and believe the reason nicotine withdrawal is easy-to-attain eVects from nicotine via important is not its severity but rather its dura- cigarettes tion.24 Multiple studies have found that the Many lay persons believe the magnitude of a average duration of withdrawal is about three reward is the most important determinant of weeks and that a substantial proportion of its eYcacy. In reality, the rapidity, frequency, smokers (> 40%) have withdrawal symptoms reliability, and ease of attainment of the reward that last longer than three weeks.24 I believe are as important, if not more important.17 I, that it is this chronic, low grade discomfort that and others before me,18 believe nicotine via undermines smoking cessation. For example, cigarette smoking is so dependence producing chronic hunger undermines many attempts to because it maximises all four of these eVects. lose weight, even though hunger on any one First, nicotine via cigarettes is absorbed via day may not be severe. In addition, I believe the lung, directly into the arterial system, with- that many smokers who are still irritable, hun- out dilution of the venous system, and reaches gry, and anxious after three weeks believe this the brain within 10 seconds.1 This is faster than is how they will be for the rest of their life with- intravenous use. I know of few rewards that out cigarettes. Faced with this possibility, it is occur quicker. Second, if one smokes 20 understandable why many smokers would cigarettes a day and takes 10 puVs per relapse. Earlier studies that focused on the cigarette, this means 200 rewards per day. I severity of withdrawal did not find withdrawal know of no other reward that occurs so undermined cessation.25 However, more frequently in daily life. Third, unlike sophisticated recent studies have found that purchasing illicit drugs on the street in which abstinent smokers whose withdrawal abates the purity varies from sale to sale, with slowly are much more likely to relapse than cigarettes, one gets exactly the same dose with those whose withdrawal abates rapidly.26 Thus, each purchase. Fourth, because of ubiquitous the evidence supports the notion that the dura- marketing and underage sales, purchasing of tion of withdrawal is important. cigarettes requires significantly less eVort than purchasing illicit drugs or alcohol. Perhaps the Implications for tobacco control

best evidence for this view is that when These four particular features of nicotine http://tobaccocontrol.bmj.com/ nicotine is delivered via medications in which dependence suggests possible changes in the delivery is slow, infrequent and costly (for tobacco control activities. The major example, transdermal nicotine), then the implication of the first view—nicotine has sev- dependence potential of nicotine is low.34 eral beneficial eVects—is that prevention programmes perhaps should stop denying this. Nicotine is not intoxicating Most smokers believe nicotine has beneficial A common criticism of defining smoking as a eVects.13 Denying such eVects undermines the nicotine dependence is that, unlike other drug credibility of prevention programmes. We do dependencies, smoking does not cause not try to deny that cocaine stimulates or that intoxication and the related extreme behav- alcohol is relaxing in prevention programmes, iours (for example, crime or violence).19 I so why deny beneficial eVects for nicotine? believe the lack of intoxication from nicotine Admitting nicotine has beneficial eVects can be on September 24, 2021 by guest. Protected copyright. makes it more addicting, not less addicting. integrated into prevention programmes by This lack of intoxication allows the smoker to pointing out that smoking is sometimes a ingest large amounts of a drug without causing “pharmacological crutch”. social problems, increasing the probability of The major implication of the second view— experiencing beneficial eVects or of physical the rapid onset of eVects, frequent administra- dependence developing. In support of this tion, reliability of action, and ease of availabil- notion, studies of other drug dependencies ity with cigarette vehicles increase the clearly indicate intoxication inhibits use in dependence potential of nicotine—is that a dependent users.20 Also, many ever users of regulatory system should acknowledge that a tobacco become daily users, but fewer ever gradual phasing towards vehicles that deliver users of alcohol and cocaine do so.21 22 This is nicotine less rapidly, that require only probably caused, in part, by the limiting eVects infrequent use, and are less easily obtainable of alcohol and cocaine intoxication. could reduce nicotine dependence.18 In addition, I believe this lack of intoxication The major implication of the third contributed to society’s tacit acceptance of view—lack of intoxication makes nicotine nicotine dependence. One can argue that much more dependence producing—is that perhaps of society’s response to drug dependence is we need to educate the public that the central based on concerns about how a drug user’s feature of drug dependence is impaired control actions will influence others. Since nicotine over drug use, not intoxication.2 This view is does not acutely disrupt families, cause especially important to transmit to adolescents violence, etc, it is easy to see how society would as many incorrectly believe that because not have a pressing need to intervene or to nicotine is not intoxicating, it has less depend- label nicotine a drug of dependence. ence potential.27

www.tobaccocontrol.com 64 Hughes Tob Control: first published as 10.1136/tc.10.1.62 on 1 March 2001. Downloaded from The major implication of the fourth Grunberg NE, Henningfield JE, Lando HA, eds. The health consequences of smoking: nicotine addiction. A report of hypothesis—the long duration of withdrawal the Surgeon General, 1988. Rockville, Maryland: Public undermines quit attempts—is that perhaps Health Service, Centers for Disease Control, OYce on Smoking and Health, 1988 (DHHS Publication No those who state withdrawal dissipates within (CDC) 88–8406.):377–458. one week need to, instead, state withdrawal 10 Hughes JR. Distinguishing withdrawal relief and direct eVects of smoking. Psychopharmacology 1991;104:409–10. does decline but often lasts a month or longer. 11 Heishman SJ. What aspects of human performance are truly Accordingly, we need to help smokers to plan enhanced by nicotine? Addiction 1998;93:317–20. 12 Parrott AC, Garnham NJ. Comparative mood states and their lives to accommodate the possibility that cognitive skills of cigarette smokers, deprived smokers and they will not be at their best for several weeks. nonsmokers. Hum Psychopharmacol 1998;13:367–76. In addition, we need to inform smokers that 13 Pomerleau CS, Pomerleau OF. Euphoriant eVects of nicotine in smokers. Psychopharmacology 1992;108:460–5. even if they are still having problems three 14 ShiVman S. Assessing smoking patterns and motives. J Con- weeks post-abstinence, this is likely to be with- sult Clin Psychol 1993;61:732–42. 15 Breslau N, Kilbey MM, Andreski P. DSM-III-R nicotine drawal and they should be feeling better in the dependence in young adults: prevalence, correlates and near future. Finally, we need to use this associated psychiatric disorders. Addiction 1994;89:743– 54. information to encourage quitters to remain on 16 Perkins KA, Stitzer M. Behavioral pharmacology of medications or in psychosocial treatments for nicotine. 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