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 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.


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 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.


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 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.


CONCLUSIONS
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.
McCaul
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The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. betsymc@jhmi.edu
Wand
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Rohde
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Lee
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D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000428:Alcohol Drinking / Q000097:blood*; D000437:Alcoholism / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000378:metabolism
D009292:Narcotic Antagonists; C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone