Effects of naltrexone and nalmefene on subjective response to alcohol among non-treatment-seeking alcoholics and social drinkers

Background: Despite the relative success of opiate antagonist medication within controlled clinical trials for alcoholism, laboratory studies have not fully examined potential mechanisms for their efficacy in alcohol-dependent persons. The present study evaluated the impact of naltrexone and nalmefene on craving and subjective effects after a moderate alcohol dose among non-treatment-seeking alcoholics (n 125) and social drinkers (n = 90). Methods: Participants were randomly assigned to receive placebo, naltrexone (titrated to 50 mg/day), or nalmefene (titrated to 40 mg/day) for seven days before an alcohol challenge clinical laboratory session. During the clinical laboratory session, a drink of alcohol (0.4 mg/kg for men, 0.34 mg/kg for women) was provided in a bar-like setting. The effects of the alcohol dose on subjective craving, stimulation, and sedation were measured before having free access to alcohol. Results: Alcoholics reported higher levels of craving than social drinkers before and after the drink as well as higher levels of alcohol-induced stimulation. Both opiate antagonist medications suppressed initial increases in craving and stimulation. Conclusions: These findings demonstrate that both naltrexone and nalmefene are associated with reduced alcohol-induced craving and stimulation among alcoholics who are not actively attempting to reduce drinking. These data provide insights into potential mechanisms that may underlie opiate antagonists' effects in the context of treatment.