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Director's Report to the National Advisory Council on Drug Abuse
February, 1996

Research Findings

Behavioral Research

Increase the Cost of Drugs and Offer Alternative Activities

In a study that recently appeared in Experimental and Clinical Psychopharmacology (3, 1995), Warren Bickel and his colleagues at the University of Vermont reported important data showing how cigarette consumption and cigarette seeking behavior can be decreased by principles derived from behavioral economics. Cigarette smokers participated in a laboratory study in which work effort ("simulated employment") reduced cigarette consumption, as did the availability of recreational activities. The greatest reductions in both cigarette smoking and effort to obtain cigarettes were achieved when smoking cost was increased in combination with the presence of alternative recreational activities. This study points out yet again that both drug seeking and consumption is not intractable and can be reduced by interventions informed by models in the basic behavioral sciences.

Female Cigarette Dependence, Relative to Male Cigarette Dependence, May Be More Strongly Linked to Non-Nicotine Factors than to Nicotine Factors

Kenneth A. Perkins, University of Pittsburgh, has a review article in press, "Sex Differences in Nicotine vs Non Nicotine Reinforcement as Determinants of Tobacco Smoking," in Experimental and Clinical Psychopharmacology. Although cigarette smoking is declining in the U.S. population, the decline is slower for women than for men and by the year 2000 women smokers are predicted to outnumber men smokers. There is evidence that women are less successful at quitting smoking than men: they are less likely to initiate quitting, and when they do quit, they are more likely to relapse than men. Moreover, nicotine replacement via nicotine gum or the nicotine patch are less effective for females than males, despite equal compliance with regimen. Dr. Perkins considers whether these sex differences in smoking cessation reflect differences in smoking for nicotine reinforcement or reflect differences in non-nicotine factors, such as the sensory aspects of smoke inhalation, conditioned responses to smoke stimuli, and social reinforcement associated with smoking. Relative to men, smoking by women may be controlled less by nicotine and more by the non-nicotine factors. For example, although quitting smoking is more difficult for women than men, data indicate that women may have lower levels of dependence, i.e., they smoke fewer cigarettes per day, smoke brands with lower nicotine yields, are less likely to report deep inhalation, and have lower scores on self-report indices of nicotine dependence. Nevertheless, their withdrawal is often more severe than that of men, and they report less withdrawal relief from nicotine gum than men. Evidence also indicates that women are more responsive to non-nicotine smoking cues than are men.

Male-Female Differences in the Use of Nicotine Nasal Spray

Dr. Kenneth Perkins, University of Pittsburgh, compared the use of nicotine nasal spray (doses corrected for body weight) in male and female smokers during smoking cessation. Males used the nicotine spray twice as much as placebo, whereas, for women, use of the nicotine and placebo sprays were similar and were equivalent to the males' use of the placebo spray. This outcome is consistent with data from an earlier study by Dr. Perkins showing that preloads of nicotine nasal spray reduced smoking in women to a lesser degree than in men, and are consistent with the notion that women, relative to men, smoke less for nicotine reinforcement and more for non-nicotine factors (e.g. sensory, social, conditioned). A possible treatment implication of this view is that for women, less emphasis should be placed on nicotine replacement therapy and more emphasis should be placed on therapy directed at identifying the non-nicotine aspects of smoking and reducing their control.

Nicotine Effects in Humans

Dr. Kenneth Perkins from the University of Pittsburgh has recently reported some significant effects related to acute nicotine tolerance and individual differences in response to nicotine. Smokers pretreated with nicotine and then given nicotine 30, 60 or 120 min. later became tolerant to the additional nicotine's mood, euphoric and cardiovascular effects. This "acute" tolerance dissipated over time, however, for other subjective measures such as arousal. These data suggest that only some of nicotine's many effects diminish between smoking episodes experienced by smokers. Psychopharmacology, 118: pp. 164-170, 1995.

In studies of sex differences, males and females do not differ in their ability to distinguish between a placebo and a nicotine spray if they have been taught to make these discriminations earlier. Without such pre-training, however, men are better able to distinguish between lower doses of nicotine and placebo than women. Moreover, women find the effects of tobacco smoking more pleasurable than nicotine spray while men find their effects equally pleasurable. Thus, women may be more sensitive to other aspects of smoking than the actual nicotine effects (such as appetite suppression; also see above). These findings have implications for the use of nicotine replacement therapy for smoking cessation in women. Dr. Perkins also has shown that the subjective state prior to nicotine administration can alter the mood and euphoric effects of nicotine. Smokers were exposed to a high-challenge (high stress) task vs low-challenge task (low stress). Smoking reduced stress during the high-challenge task, but not the low-challenge task. These and other results suggest that nicotine's subjective effects are related to the person's presmoking state, and that nicotine may be reinforcing because it normalizes mood rather than has a single immutable mood-altering effect. A review of this research is presented in Behavior Genetics, 25: pp. 119-131, 1995.

Effects of Naltrexone Pretreatment on the Subjective and Performance Effects of Ethanol in Social Drinkers

P. Doty and H. de Wit, Behavioral Pharmacology, 6: pp. 386-394, 1995, report that naltrexone (25 or 50 mg) produces few subjective effects and does not impair psychomotor performance or verbal recall performance in social drinkers. Importantly, naltrexone pretreatment did not alter the subjective or performance effects of a dose of ethanol (0.5 g/kg) chosen to produce a moderate level of subjective effects in social drinkers. These data are interesting because in an alcoholic population, naltrexone has maintained abstinence, decreased craving, and prevented relapse. To better understand the factors influencing naltrexone/ethanol interactions, Dr. de Wit suggests that future research should explore variables including the study population (differences in baseline alcohol use or genetics), duration of naltrexone treatment (acute vs chronic), and ethanol dose studied.

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