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J Addict Med. 2018 May/Jun;12(3):227-233. doi: 10.1097/ADM.0000000000000392.

Effects of Varenicline Alone and in Combination With Low-dose Naltrexone on Alcohol-primed Smoking in Heavy-drinking Tobacco Users: A Preliminary Laboratory Study.

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Yale School of Medicine, Department of Psychiatry, New Haven, CT (WR, SAM), and Yale School of Medicine, Department of Internal Medicine, New Haven, CT (JMS, JMT).



Heavy-drinking tobacco users are less likely to successfully quit smoking than their moderate-drinking counterparts, even when they are prescribed smoking cessation medication. One strategy for improving treatment outcomes in this subgroup of tobacco users may be to combine medication therapies to target both alcohol and tobacco use simultaneously. Adding naltrexone to frontline smoking cessation treatments may improve treatment outcomes in this group.


This double-blind, placebo-controlled human laboratory study examined the effects of varenicline (2 mg/d) and varenicline (2 mg/d), combined with a low dose of naltrexone (25 mg/d) on alcohol-primed smoking behavior in a laboratory model of smoking relapse in heavy-drinking tobacco users (n = 30). Participants attended a laboratory session and received an alcohol challenge (target breath alcohol concentration = 0.030 g/dL). They completed a smoking delay task that assessed their ability to resist smoking followed by an ad libitum smoking phase (primary outcomes). They also provided ratings of subjective drug effects and craving, and carbon monoxide levels were measured after smoking (secondary outcomes).


Participants receiving varenicline monotherapy delayed smoking longer and smoked fewer cigarettes than those on placebo. Participants receiving varenicline + low-dose naltrexone did not delay smoking longer than those receiving varenicline alone. Participants in both active medication arms smoked fewer cigarettes ad libitum than those receiving placebo.


Varenicline can improve smoking outcomes even after an alcohol prime, supporting its use in heavy drinkers who wish to quit smoking. Findings did not support increased efficacy of combined varenicline + low-dose naltrexone relative to varenicline monotherapy.

[Available on 2019-05-01]

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