Naltrexone for alcohol use disorder
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Naltrexone for Alcohol Use Disorder: A Comprehensive Review
Introduction to Naltrexone and Alcohol Use Disorder
Naltrexone, an opioid receptor antagonist, has been extensively studied for its efficacy in treating alcohol use disorder (AUD). This article synthesizes findings from multiple research studies to provide a clear understanding of how naltrexone impacts alcohol consumption, craving, and related outcomes in various populations.
Efficacy of Naltrexone in Reducing Alcohol Consumption
General Population
Naltrexone has been shown to reduce alcohol consumption and craving in individuals with AUD. A meta-analysis revealed that naltrexone decreases alcohol craving (Hedges g = -0.252) and stimulation (g = -0.223), while increasing sedation (g = 0.251) and negative mood (g = 0.227) during alcohol consumption 4. These effects suggest that naltrexone can make drinking less pleasurable and more aversive, thereby reducing the desire to drink.
Sexual and Gender Minority Men
A targeted study on sexual and gender minority men (SGM) with mild to moderate AUD found that naltrexone significantly reduced the number of binge-drinking days, drinks per month, and alcohol craving scores during a 12-week treatment period. These effects were sustained at six months post-treatment, indicating long-term benefits 1.
Adolescents
In adolescents with problematic drinking patterns, naltrexone moderated the association between alcohol use and affect. Specifically, higher blood alcohol concentration levels were associated with greater negative affect (NA) later in drinking episodes, and greater NA after the first drink was linked to reduced subsequent alcohol consumption 2. This suggests that naltrexone may help disrupt the reinforcing cycle of alcohol use and negative emotions in young drinkers.
Naltrexone in Special Populations
Bipolar Disorder
A pilot study on patients with bipolar disorder and alcohol dependence indicated that naltrexone might reduce drinking days and alcohol craving, although the results were not statistically significant. The study highlighted the need for larger trials to confirm these findings 3.
Pathological Gambling
In individuals with concurrent alcohol use disorder and pathological gambling, naltrexone did not show significant differences in alcohol or gambling outcomes compared to placebo. However, the overall treatment, including cognitive-behavioral counseling, was effective in reducing these behaviors 8.
Genetic Factors and Naltrexone Response
A study examining the role of the Asn40Asp polymorphism of the μ-opioid receptor gene (OPRM1) found no significant genotype-treatment interaction on the primary outcome of heavy drinking. This suggests that the Asp40 allele does not predict naltrexone treatment response, and it is premature to use this polymorphism as a biomarker for naltrexone efficacy 5.
Comparative Effectiveness of Naltrexone
A systematic review and meta-analysis comparing naltrexone with other pharmacological treatments for AUD found that naltrexone is more effective in reducing heavy drinking and craving, while acamprosate is better at promoting abstinence. The review also noted that requiring abstinence before treatment enhances the efficacy of naltrexone 9.
Mechanisms of Action
Naltrexone's efficacy is partly attributed to its ability to activate the hypothalamo-pituitary-adrenocortical (HPA) axis, leading to higher cortisol levels and reduced alcohol craving. This mechanism was confirmed in a laboratory study where naltrexone-treated subjects drank fewer drinks and reported lower craving levels compared to placebo 10.
Conclusion
Naltrexone is a valuable pharmacotherapy for reducing alcohol consumption and craving in individuals with alcohol use disorder. Its efficacy is supported across various populations, including sexual and gender minority men, adolescents, and those with co-occurring bipolar disorder. While genetic factors like the Asn40Asp polymorphism do not predict treatment response, naltrexone's ability to alter the subjective experience of alcohol and activate the HPA axis underpins its effectiveness. Further research is needed to optimize its use in specific subgroups and in combination with other treatments.
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Most relevant research papers on this topic
Targeted Oral Naltrexone for Mild to Moderate Alcohol Use Disorder Among Sexual and Gender Minority Men: A Randomized Trial.
Targeted oral naltrexone significantly reduced binge-drinking outcomes in sexual and gender minority men with mild to moderate alcohol use disorder, with sustained effects at 6 months posttreatment.
RCTNaltrexone Moderates the Association of Alcohol Use and Affect Among Adolescent Drinkers in Daily Life.
Naltrexone can disrupt the association of affect and alcohol use in adolescents, potentially benefiting psychotherapy.
RCT
Very Rigorous JournalA randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence.
Naltrexone shows potential value and acceptable tolerability in reducing alcohol use and cravings in bipolar disorder patients, with response linked to medication adherence.
RCT
Rigorous Journal
Highly CitedNaltrexone effects on subjective responses to alcohol in the human laboratory: A systematic review and meta‐analysis
Naltrexone reduces alcohol cravings, stimulation, sedation, and negative mood in laboratory settings, with effects varying by alcohol use severity.
Meta-AnalysisRigorous JournalNaltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial.
The Asp40Asp polymorphism does not predict the response to naltrexone treatment for alcohol dependence, making it premature to use it as a biomarker.
RCTHighly CitedNaltrexone in the treatment of alcohol dependence.
Naltrexone does not show significant improvement in relapse rates or drinking frequency for men with chronic, severe alcohol dependence compared to placebo.
RCT
Large Human TrialHighly CitedPharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta‐analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate
Pharmacological treatment for alcohol dependence or alcohol use disorders shows low to medium efficacy in reducing drinking, but no clear benefits on health outcomes.
Meta-AnalysisHighly CitedA randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of concurrent alcohol use disorder and pathological gambling.
Naltrexone's effectiveness in treating concurrent alcohol use and pathological gambling problems was not supported in a randomized, double-blind, placebo-controlled trial.
RCTMeta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?
Acamprosate is slightly more effective in promoting abstinence and naltrexone slightly more effective in reducing heavy drinking and craving, with detoxification before treatment or longer required abstinence periods enhancing their effects.
Meta-AnalysisHighly CitedNaltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo–pituitary–adrenocortical axis
Naltrexone reduces alcohol cravings and consumption in alcohol-dependent individuals, potentially due to its ability to activate the hypothalamo-pituitary-adrenocortical axis.
RCTHighly Cited