Alcohol use disorder (AUD) is a prevalent condition associated with high degree of comorbidity and mortality. Among the few approved pharmacotherapies for AUD, two involve opioid receptor antagonism. Naltrexone and nalmefene are thought to act via opioid receptor blockage to reduce neural response to alcohol and drug-associated cues and consumption, but there have been limited efforts to characterize these effects in humans. In these studies, we sought to test the magnitude of opioid antagonism effects on neural response to monetary rewards in two groups: light drinkers (for the naltrexone study) and heavy drinkers (for the nalmefene study). We conducted double-blind, randomized, crossover pilot studies of reward activation in the brain following acute administration of opioid antagonist and placebo in 11 light and 9 heavy alcohol users. We used a monetary incentive delay task during functional MRI. We found a main effect of cue type on BOLD activation in the nucleus accumbens, demonstrating a neural reward response. The effect of opioid antagonism, relative to placebo, was small and nonsignificant for reward activation in the accumbens for both light and heavy alcohol users. Based on the results of two pilot studies, opioid antagonist medications do not appear to decrease neural activation to monetary rewards in the nucleus accumbens relative to placebo.
Trial registration: ClinicalTrials.gov NCT04854551 NCT02639273.
Keywords: Naltrexone; alcohol use disorder; functional MRI; monetary incentive delay; nalmefene; opioid antagonism; pharmacotherapy; reward activation.