Clearing the Smoke Assessing the Science Base for Tobacco Harm Reduction (2001) / Chapter Skim
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isomer in the late 1970s (Domino, 1999~. Up to 10% of the nicotine in tobacco smoke is the (R)
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, p-endorphin (mood modulation and analgesia) , and 6aminobutyric acid.
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Furthermore, individuals experience greater positive affect when smoking after a period of abstinence. The relief of negative affect by tobacco use may be more a function of abating withdrawal symptoms (Cinciripini et al., 1997; RCP, 2000~.
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for cigarette smokers (Figure 9-1~. Nicotine is well tolerated as a dermal application, even in individuals who suffer from irritant skin disorders (Benowitz, 1995~.
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Cigarettes Oral Snuff ~ It] 11 1 1 1 1 1 1 1 1 1 1 1 1 Chewing Tobacco Nicotine Gum ~ ~ 1~ 1''~ 2-2-2-2-2-2-2-2-2-2-2-2-2-2~ '1 ~ 1 1 60 90 120 300 30 Minutes 60 90 120 NOTE: Blood nicotine concentrations during and after cigarette smoking for nine minutes, oral snuff (2.5 grams)
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248 CLEARING THE SMOKE ingestion. The evoked liking, systemic response, and addiction potential of the former pattern of nicotine delivery exceed those of the latter (Benowitz et al., 1988~.
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Thus, the hazard to the fetus of maternal cigarette smoking is well established (Oncken et al., 1998; Robinson et al., 2000) , whereas the theoretically much smaller risk of NRT remains entirely notional.
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NICOTINE PHARMACOLOGY 40 30 0 20c' of F 10an o ._ c' o C) o 0 m O ~ 1 1 1 1 1 1 1 400 360 280 240 200 Y ~ _ _ 0800 1200 1600 2000 Clock Time 251 2400 0400 0800 FIGURE 9-4 Circadian blood concentrations of nicotine and cotinine during unrestricted smoking.
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From page 252... ...
By contrast, desensitization of vascular or central receptors by nicotine may contribute to the lower blood pressure observed in chronic smokers (Charlton and While, 1995~. The mechanisms involved in mediating the adverse effects of cigarette smoking and of smokeless tobacco on the cardiovascular system are poorly understood, but are thought to include induction of an adverse lipoprotein profile (Allen et al., 1994)
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Controlled studies have demonstrated that switching from cigarette smoking to NRT is associated with amelioration of the lipoprotein and hemostatic profiles (Allen et al., 1994; Ludviksdottir et al., 1999; Winther and Fornitz, 1999) and a reduction in platelet activation (Nowak et al., 1987~.
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Physical addiction to nicotine is associated with euphoriant and other psychoactive effects, the development of tolerance, and the experience of withdrawal symptoms
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These withdrawal symptoms peak during the first week of abstinence and return to baseline levels by four weeks (Hughes et al., 1990a)
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Subjective effects, the desire to use more of a drug, and the actual self-administration of a drug are functions of absorption rate (Henningfield and Keenan, 1993~. Therefore, whereas cigarettes have high abuse potential, nicotine patches have lower abuse potential.
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However, deciphering whether this persistent TABLE 9-1 Measures of Dependence or Addiction and Abuse Liability Measures for Dependence or Severity of Dependence Daily or regular smoking (cotinine level) DSM criteria International Diagnostic Code Surgeon General's report, 1988 Fagerstrom Tolerance Questionnaire Fagerstrom Nicotine Dependence Test Methods to Assess for Addiction or Abuse Liability Surveys Daily use or dependence among the general population Daily use or dependence among those exposed to the drug Escalation of drug use Relapse rates Laboratory models Psychoactive or subjective effects Drug discrimination Conditioned place preference Drug self-administration Withdrawal
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guidelines, abuse liability is determined by two primary factors (see deWit and Zacny, 1995~. One is the likelihood of repeated use, which is determined by the drug's psychoactive, positive reinforcing effects and the extent to which it can relieve withdrawal symptoms as a result of chronic use.
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In fact, many cigarette smokers exhibit at least as many indicators of dependence as other drug users and abusers (CDC, 1995b; U.S.
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Researchers have used meeting a specified number of these symptoms as proxy measures for the DSM-IV criteria for substance dependence. In some assessments, individual items, such as experiencing withdrawal symptoms or difficulty quitting have been of particular focus as indicators of dependence (CDC, 1994, 1995a, b)
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The criteria for diagnosis were based on the DSM-IV method in which smokers must experience three or more of seven indicators of dependence. The findings showed that while 8.6% of the general population 12 years and older met criteria for nicotine dependence, 28% of those who had used tobacco products in the past year experienced nicotine dependence.
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No data are available on the prevalence of daily use in the general population or on dependence on these products according to diagnostic criteria for dependence or FTND scores. The rate of persistent use of nicotine replacement products among smokers enrolled in clinical trials who were assigned these products is much lower than the rate of persistent use of cigarettes, ranging from 9% for nicotine gum to 18% for nicotine nasal spray (Hughes, 1998~.
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Several methods have been developed using clinical and animal models to determine the addiction potential or abuse liability of a drug. These include models of self-administration, drug discrimination, and conditioned drug placement.
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Drug A or B can be two different doses of a drug, different types of drugs, or an active and placebo drug. · The conditioned place preference model also is used to determine the abuse liability of a drug.
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as well as to self-administer greater number of doses of nicotine nasal spray (Perkins et al., 1997) and nicotine gum (Hughes et al., l990b)
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Cessation of smokeless tobacco use generally produces less intense withdrawal symptoms than cessation of cigarette smoking (Hatsukami et al., 1987; Keenan et al., 1989~. However, in a population of smokeless tobacco users enrolled in clinical trials, the severity and number of withdrawal symptoms from smokeless tobacco were comparable to those experienced by cigarette smokers who were trying to quit (Hatsukami et al., 2000~.
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There is some evidence of differences in the pharmacodynamic effects of nicotine between genders and of an influence of timing in the menstrual cycle on the response to NRT and the success of attempts to quit (Pomerlau et al., 1991; Gritz et al., 1996~. Women appear to have more pronounced withdrawal symptoms during the late luteal phase of the menstrual cycle, and it has been suggested that fear of weight gain, confidence in the ability to quit,
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Cigarette smoking is associated with lower body weight and quitting is associated with weight gain. Involvement in a weight control program amplifies the efficacy of NRT (Danielsson et al., 1999~.
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Cigarette smoking reduces the hypotensive response to p-blockers (Fox et al., 1984) , but the contribution of nicotine to this effect is unknown.
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For example, observations suggesting that nicotine impairs endothelial function, a property it shares with cigarette smoking, raise concerns about its effect on atherogenesis during long-term usage. Such an effect may take many years to emerge and highlights the importance of continued postmarketing surveillance of NRT.
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1993. Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking.
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Clin Pharmacol Ther 44~1~:23-28. Berlin I, Said S
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Clin Pharmacol Ther 67~4~:391-397. Charlton A, While D
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Proc Natl Acad Sci U S A 94~2~:587-592. Frydman M
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1995. Gender and the effects of different doses of nicotine gum on tobacco withdrawal symptoms.
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J Pharmacol Exp Ther 252~3~:11751183. Hughes JR, Gust SW, Keenan R
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1999. Effects of nicotine nasal spray on atherogenic and thrombogenic factors during smoking cessation.
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1996. Effects of smoking cessation on insulin and cardiovascular risk factors a controlled study of 4 months' duration.
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1994b. Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray.
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Cancer Epidemiol Biomarkers Prev 7~6~:453-458. Shiffman S
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Is there a role for antioxidant micronutrient supplementation? Clin Chest Med 21~1~:173-187, x.
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1999. The effect of cigarette smoking and nicotine chewing gum on platelet function and fibrinolytic activity.
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