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

Abstract

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. Methods This double-blind, placebo-controlled preliminary investigation examined the effects of varenicline (0, 1, 2 mg/day) on subjective reactivity, cognition, perceptual motor function, and physiologic reactivity to a fixed-dose of alcohol (vs. non-alcohol control beverage) using an established laboratory paradigm in smokers and non-smokers meeting criteria for alcohol use disorders (AUDs; n=44). All participants had completed a parent varenicline study evaluating alcohol self-administration. Each subject completed two fixed-dose laboratory sessions assessing reactivity to a high-dose alcohol (0.08 g/dL) or a non-alcoholic control beverage, order counter-balanced. 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 non-specific effects on diastolic blood pressure and heart rate. Overall, there were few differences in effects between 1 mg/day and 2 mg/day 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.

Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol‐Preferring (P) Rats

“…Early reports of VAR‐induced altered behavior, which resulted in a 2015 FDA warning regarding the use of VAR, were not substantiated and the FDA revised the warning in 2016 and stated that VAR does not pose serious mental health risks. Importantly, there appears to be minimal side effects of VAR reported in individuals with AUD (McKee et al., ; Mitchell et al., ; Verplaetse et al., ,b).…”

A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking

“…The beta‐endorphin response to alcohol is heritable (Froehlich et al., ) and the response is greater in individuals with a family history of alcoholism than it is in individuals without a family history of alcoholism (Gianoulakis et al., ). Both NTX and VAR reduce alcohol‐induced feelings of intoxication and well‐being and reduce alcohol drinking (Chick et al., ; Childs et al., ; Froehlich et al., ; Hendershot et al., ; Litten et al., ; McKee et al., ; O'Malley and Froehlich, ; Verplaetse et al., ; Volpicelli et al., ). NTX is more effective in decreasing alcohol drinking in individuals with a family history of alcoholism (“family history positive” or “high risk”) than in individuals without a family history of alcoholism (Krishnan‐Sarin et al., ; Monterosso et al., ).…”

Effects of varenicline on alcohol cue reactivity in heavy drinkers

“…All participants were heavy drinkers who reported consuming > 7 (women) or 14 (men) drinks per week and > 3 (women) or > 4 (men) drinks per episode in the last 30 days. Participants were recruited as part of larger series of sequential human laboratory studies, the results of which are reported elsewhere (McKee et al 2009; Verplaetse et al 2016a; Verplaetse et al 2016b). Data reported in McKee et al (2009) and Verplaetse et al (2016a) were collected 8 post-randomization and reported on ad-libitum drinking outcomes.…”

“…Data reported in McKee et al (2009) and Verplaetse et al (2016a) were collected 8 post-randomization and reported on ad-libitum drinking outcomes. Data reported in Verplaetse et al (2016b) were collected between 2 and 3 weeks post-randomization and reported on reactivity to a high dose of alcohol. Data reported in the current manuscript has not been previously published and were collected on a separate laboratory session (day 10 post-randomization).…”

“…These data were collected as part of a larger series of sequential laboratory studies examining the effects of varenicline on alcohol use (McKee et al 2009; Verplaetse et al 2016ab). The primary goal of this study was to determine whether varenicline reduces alcohol-cue-induced craving.…”