The GABA-B receptor agonist baclofen has been investigated and used as a treatment for alcohol use disorder, but data from clinical studies remain inconsistent. Additional research is needed to understand the biobehavioral mechanisms underlying baclofen’s effect in relation to alcohol use. In the present study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in an experiment in a bar-like laboratory. The experimental session consisted of three procedures: alcohol cue-reactivity, priming, and self-administration. Repeated blood samples were also collected for pharmacokinetic measurements. Baclofen, compared to placebo, did not significantly reduce alcohol craving or drinking in aggregate analyses. However, compared to placebo, the link between alcohol priming and self-administration was disrupted under baclofen, suggesting that baclofen may work by uncoupling the link between an initial drink and subsequent alcohol consumption. In addition, considerable inter-individual variability in baclofen pharmacokinetic parameters was observed. Finally, maximum plasma concentrations of baclofen negatively correlated with cue-induced alcohol craving and ratings of alcohol-induced ‘liking more’. These findings provide novel insights into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consummatory behaviors in heavy-drinking alcohol-dependent individuals.
Mol Psychiatry, 2018, ISSN: 1476-5578 (Electronic); 1359-4184 (Linking).