Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings.

BACKGROUND Varenicline has been found to decrease alcohol-motivated behaviors. Recent warnings regarding aversive events associated with varenicline used in conjunction with alcohol warrant further investigation into the safety of the drug when combined with alcohol. The purpose of this preliminary investigation was to examine the effect of combining varenicline with a high, fixed dose of alcohol on subjective reactivity and cognitive function in adults with alcohol use disorders (AUDs). METHODS This double-blind, placebo-controlled preliminary investigation examined the effects of varenicline (0, 1, 2 mg/d) on subjective reactivity, cognition, perceptual motor function, and physiologic reactivity to a fixed dose of alcohol (vs. nonalcohol control beverage) using an established laboratory paradigm in smokers and nonsmokers meeting criteria for AUDs (n = 44). All participants had completed a parent varenicline study evaluating alcohol self-administration. Each subject completed 2 fixed-dose laboratory sessions assessing reactivity to a high-dose alcohol (0.08 g/dl) or a nonalcoholic control beverage, order counterbalanced. RESULTS Varenicline attenuated alcohol-related increases in subjective intoxication and alcohol-related decreases in executive cognitive function. At baseline, varenicline reduced alcohol craving and diastolic blood pressure, and increased associative learning, working memory, and perceptual motor function. Varenicline produced nonspecific effects on diastolic blood pressure and heart rate. Overall, there were few differences in effects between 1 and 2 mg/d varenicline versus placebo. CONCLUSIONS These preliminary results continue to support the safety and use of varenicline in combination with alcohol in individuals meeting criteria for AUDs.