Naltrexone effects on subjective responses to alcohol in the human laboratory: A systematic review and meta-analysis

Naltrexone (NTX) has been widely studied for the treatment of alcohol use disorder with overall support for its efficacy. The mechanisms of action of naltrexone are thought to involve attenuation of the hedonic effects of alcohol and potentiation of its aversive effects. In order to provide a quantitative estimate of the effects of naltrexone on subjective response to alcohol, the aims of this meta-analytic review are to examine the effects of naltrexone across four domains of subjective response. Meta-analyses of naltrexone effects on alcohol craving (k = 16, N = 686), stimulation (k = 15, N = 675), sedation (k = 18, N = 777), and negative mood (k = 9, N = 281) suggested that under laboratory conditions and compared with placebo, naltrexone reduces craving (Hedges g = -0.252; SE = 0.054; 95% CI, -0.375 to -0.130; P < 0.01), reduces stimulation (g = -0.223; SE = 0.067; 95% CI, -0.372 to -0.074; P < 0.01), increases sedation (g = 0.251; SE = 0.064; 95% CI, 0.112-0.389; P < 0.01), and increases negative mood (g = 0.227; SE = 0.047; 95% CI, 0.100-0.354; P < 0.01). Results were robust when drinks per month and alcohol dose were added to the models as covariates. The effects of naltrexone varied by severity of alcohol use with medication effects on craving and stimulation being observed in sample of both heavy drinkers and AUD individuals. These results are consistent with the hypothesized mechanisms of action of NTX, although the effects are of small magnitude. This meta-analysis aggregates across multiple human laboratory studies of NTX's effects on subjective response to alcohol, providing a comprehensive summary of a key mechanism of NTX efficacy, namely, alteration of the subjective experience of alcohol.