Drug and Alcohol Dependence 75 (2004) 55–65 Pretreatment with transdermal nicotine enhances some of ethanol’s acute effects in men Elena M. Kouri, Elissa M. McCarthy, Alejandra H. Faust, Scott E. Lukas ∗ Behavioral Psychopharmacology Research Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA Received 21 May 2003; received in revised form 7 January 2004; accepted 23 January 2004 Abstract Nicotine and alcohol are often consumed together and smokers are more likely than non-smokers to drink alcohol. In spite of the high prevalence of the combined use of alcohol and nicotine, only a few laboratory studies have examined the effects of this drug combination in humans. The present study was conducted to further investigate the nature of nicotine/alcohol interactions by examining whether nicotine pretreatment via a transdermal patch (placebo or 21 mg) alters the subjective and physiologic effects of acute ethanol (0.4 and 0.7 g/kg) administration. Twelve male smokers who drank alcohol on an occasional basis provided informed consent to participate in the study. Subjective reports of feeling drunk, feeling ethanol’s effects and ethanol-induced euphoria were increased by nicotine pretreatment. In addition, reports of desire to smoke a tobacco cigarette were significantly elevated after ethanol administration and were most pronounced during the active nicotine conditions. Heart rate was elevated by nicotine and ethanol-induced increases in heart rate were enhanced by nicotine pretreatment. The time to peak ethanol concentration was faster in the nicotine-patch condition and this paralleled the more rapid detection of ethanol effects after drinking the low-dose beverage. These findings suggest that nicotine enhances some of the positive subjective effects of acute ethanol and may help explain the high prevalence of the combined use of these two drugs. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Transdermal nicotine; Alcohol; Polydrug use; Tobacco smoking 1. Introduction Nicotine and alcohol are often consumed together and smokers are more likely than non-smokers to drink alcohol (Shiffman et al., 1994; Keenan et al., 1990). It is estimated that 90% of smokers drink alcohol regularly compared to 60% of non-smokers (Kozlowski and Ferrance, 1990) and that 35% of heavy smokers have a history of alcohol depen- dence compared to 10% of never-smokers (Hughes, 1995). Similarly, alcohol drinkers are more likely than non-drinkers to smoke tobacco and there is a positive correlation be- tween the amount of alcohol consumed and the amount of cigarettes smoked (Cummings et al., 1981; Istvan and Matarazzo, 1984; Sobell et al., 1990). In spite of the high prevalence of the combined use of alcohol and nicotine, only a few laboratory studies have examined the effects of this drug combination in humans. ∗ Corresponding author. Tel.: +1-617-855-2767; fax: +617-855-3711. E-mail address: lukas@mclean.harvard.edu (S.E. Lukas). Results from studies investigating smoking behavior follow- ing alcohol pretreatment have shown that alcohol increases the amount and rate of cigarette smoking (Griffiths et al., 1976; Mello et al., 1980, 1987; Keenan et al., 1990). These effects appear to be more robust when blood alcohol levels are rising (Mitchell et al., 1995). Studies investigating the acute effects of nicotine and alcohol have found that this drug combination results in additive cardiovascular and subjective effects (Benowitz et al., 1986; Perkins et al., 1995). Specifically, when used together, tobacco and alcohol produce increases in heart rate that are greater than those seen following either drug alone, increasing the potential for cardiovascular pathology (Regan, 1990). In addition, intranasal nicotine enhanced alcohol’s stimulating effects shortly after drinking, when blood alcohol levels were as- cending, and attenuated reports of alcohol-induced sedation when blood alcohol levels were descending (Perkins et al., 1995). It is plausible that nicotine-induced enhancement of alcohol’s “stimulatory” effects as well as a reduction of it’s aversive sedating effects may reinforce the use of these substances together and help explain the high 0376-8716/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2004.01.011