Serum 6-beta-naltrexol levels are related to alcohol responses in heavy drinkers

Background: There is strong evidence for the role of the endogenous opioid system in alcohol reinforcement and consumption; however, recent human labo ratory studies and clinical trials have reported mixed effects of naltrexon e (a nonselective opioid antagonist) on alcohol-related behaviors. This pap er reports a secondary data analysis of a human laboratory study that exami nes the relationship between serum levels of 6-beta-naltrexol, the major, b iologically active metabolite of naltrexone, and subjective effects of alco hol. Methods: The study used a within-subjects design to examine the effects of naltrexone (0, 50, and 100 mg/day) on subjective responses to alcohol (none , moderate, and high dose) in heavy drinkers (n = 23). Each subject receive d three doses of naltrexone in random order; each naltrexone dose was admin istered over an 8 day period on an inpatient unit, with a 1 week outpatient washout between doses. After stabilization at each of the naltrexone doses , subjects participated in three alcohol challenge sessions (none, moderate , and high dose) in random order; thus, each subject participated in a tota l of nine alcohol administration sessions. Results: Doubling the naltrexone dose (50 vs. 100 mg/day) doubled the mean serum 6-beta-naltrexol levels. At each naltrexone dose, there was a 4-fold range in 6-beta-naltrexol levels across subjects. Before alcohol administra tion, higher 6-beta-naltrexol levels were associated with higher ratings of sedation. After high-dose alcohol administration, higher 6-beta-naltrexol levels were associated with significantly lower ratings of liking and best effects. Conclusions: These findings provide further evidence of the involvement of the opioid system in the modulation of alcohol effects and suggest that ser um 6-beta-naltrexol concentrations may be important in predicting therapeut ic response to naltrexone.