Serum 6‐Beta‐Naltrexol Levels Are Related to Alcohol Responses in Heavy Drinkers

Abstract

There is strong evidence for the role of the endogenous opioid system in alcohol reinforcement and consumption; however, recent human laboratory studies and clinical trials have reported mixed effects of naltrexone (a nonselective opioid antagonist) on alcohol-related behaviors. This paper reports a secondary data analysis of a human laboratory study that examines the relationship between serum levels of 6-beta-naltrexol, the major, biologically active metabolite of naltrexone, and subjective effects of alcohol. 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 received three doses of naltrexone in random order; each naltrexone dose was administered 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 total of nine alcohol administration sessions. 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 administration, 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. These findings provide further evidence of the involvement of the opioid system in the modulation of alcohol effects and suggest that serum 6-beta-naltrexol concentrations may be important in predicting therapeutic response to naltrexone.