Effects of Naltrexone on Alcohol Sensitivity and Genetic Moderators of Medication Response: A Double-blind Placebo-Controlled Study
Abstract
CONTEXT: Clinical trials have suggested a modest effect of naltrexone as a pharmacotherapy for alcoholism, and a recent study has suggested that the effects may be moderated by variations in the mu-opioid receptor gene (OPRM1). However, the mechanism by which naltrexone may be differentially effective as a function of the OPRM1 genotype is unclear. OBJECTIVES: (1) To replicate and expand on the association between the A118G single nucleotide polymorphism(SNP) of the OPRM1 gene and alcohol sensitivity, (2) to examine the effects of naltrexone on alcohol sensitivity, and (3) to test the A118G SNP of the OPRM1 gene as a moderator of the effects of naltrexone on alcohol sensitivity. DESIGN: A within-subject, double-blind, placebo-controlled laboratory trial of naltrexone. SETTING: Participants were recruited from the community. PARTICIPANTS: Non-treatment-seeking heavy drinkers were enrolled in the study. Prospective genotyping was conducted to oversample for the genetic variant of interest. Intervention After taking naltrexone (50 mg) or placebo, participants completed an intravenous alcohol challenge session in which they were assessed at baseline and at each of the 3 target breath alcohol concentrations: 0.02, 0.04, and 0.06 mg/L. MAIN OUTCOME MEASURES: The Biphasic Alcohol Effects Scale, the Alcohol Urge Questionnaire, the Profile of Mood States, and the Alcohol Rating Scale were administered. RESULTS: Individuals with at least 1 copy of the G allele reported lower alcohol craving and higher alcohol-induced "high" across rising breath alcohol concentrations. Naltrexone was found to blunt alcohol's effects on stimulation, positive mood, craving, and enjoyment. The effects of naltrexone on blunting alcohol-induced high were stronger among individuals with the G allele. CONCLUSION: This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy.
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Altering euphoric and pleasurable effects of alcohol is hypothesized to underlie in part the efficacy of opioid receptor antagonists, including naltrexone and nalmefene.
“The findings may have relevance to medication development, as altering euphoric and pleasurable effects of alcohol would be important targets for novel treatments and are hypothesized to underlie in part the efficacy of opioid receptor antagonists, including naltrexone and nalmefene(67–76).”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [76]
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Self-citation
- Authors
- Ray, L. A., & Hutchison, K. E.
- Affiliations
- University of Colorado Boulder (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2007-09-01
- Volume
- 64
- Issue
- 9
- Pages
- 1069
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2104372273
- Cited by
- 258
- References
- 74
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 9 · 2021: 2 · 2020: 6 · 2019: 7 · 2018: 13 · 2017: 11 · 2016: 12 · 2015: 17 · 2014: 20 · 2013: 15 · 2012: 36
- FWCI
- 17.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA14847, AA012238, F31AA014847)
- National Center for Research Resources (M01RR-00051, M01RR000051)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- naltrexone, alcohol sensitivity, OPRM1, genetic moderators, pharmacotherapy response, alcohol craving, heavy drinkers
- MeSH terms
- Adult, Alcohol Drinking, Ethanol, Alcoholism, Breath Tests, Double-Blind Method, Emotions, Female, Genotype, Humans, Male, Naltrexone, Narcotic Antagonists, Pharmacogenetics, Placebos, Prospective Studies, Reward, Genetic Variation, Behavior, Addictive, Receptors, Opioid, mu, Polymorphism, Single Nucleotide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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