Real-time assessment of alcohol craving and naltrexone treatment responsiveness in a randomized clinical trial

This secondary data analysis examined whether and how the dopamine receptor D₄ gene (DRD4) influenced naltrexone treatment responsiveness in a randomized clinical trial. We leveraged intensive experience sampling methods to test the hypothesis that craving recorded at drinking and non-drinking moments would mediate naltrexone effects on the likelihood of heavy drinking, but only among carriers of the DRD4 long (DRD4-L) allele.

Participants (M_age=29.8years, SD=12.1) were non-treatment seeking heavy drinkers (n=104, 54.8% female, 61.5% alcohol dependent) randomized to 3weeks of daily naltrexone (50mg) or placebo. During these 3weeks, participants used handheld electronic devices to complete real-time reports of alcohol use and craving multiple times per day in their natural environments. This approach afforded intensive repeated assessment of focal variables and provided in-the-moment data to test whether craving when not drinking or early in drinking episodes explained naltrexone effects on drinking.

Moderated-mediation multilevel structural equation models showed that craving during non-drinking moments mediated the treatment effect of naltrexone on heavy drinking but only among carriers of the DRD4-L allele. The same pattern of associations was not shown when evaluating craving while participants were consuming alcoholic beverages.

Findings provide the first in vivo evidence that, among carriers of the DRD4-L allele, naltrexone blunts craving in real-world settings, and this effect in turn reduces the likelihood of heavy drinking. This work highlights the utility of EMA methods for elucidating how treatments work and further demonstrates the importance of genetic factors for understanding individual differences in pharmacotherapy responsiveness.