Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Opioid Antagonists and the A118G Polymorphism in the μ-Opioid Receptor Gene: Effects of GSK1521498 and Naltrexone in Healthy Drinkers Stratified by OPRM1 Genotype.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Lack of associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with alcohol dependence: review and meta-analysis of retrospective controlled studies.BMC medical genetics · 2017Pooled it
- An analysis of the effect of mu-opioid receptor gene (OPRM1) promoter region DNA methylation on the response of naltrexone treatment of alcohol dependence.The pharmacogenomics journal · 2020Trial
- Neuroimaging findings from an experimental pharmacology trial of naltrexone in heavy drinkers of East Asian descent.Drug and alcohol dependence · 2019Trial
- Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.Alcoholism, clinical and experimental research · 2018Trial
- Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Expectation Modulates Hedonic Experiences and Midbrain Responses to Sweet Flavor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Association of theJournal of psychopharmacology (Oxford, England) · 2021Article
- Improving translation of animal models of addiction and relapse by reverse translation.Nature reviews. Neuroscience · 2020Review
- Building better strategies to develop new medications in Alcohol Use Disorder: Learning from past success and failure to shape a brighter future.Neuroscience and biobehavioral reviews · 2019Review
- Pharmacogenetics of alcohol use disorder treatments: an update.Expert opinion on drug metabolism & toxicology · 2019Review
- Increased ethanol drinking in "humanized" mice expressing the mu opioid receptor A118G polymorphism are mediated through sex-specific mechanisms.Brain research bulletin · 2018Article
- Evidence for a Long-Lasting Compulsive Alcohol Seeking Phenotype in Rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- The frequency ofAnnals of general psychiatry · 2018Article
- Promising pharmacogenetic targets for treating alcohol use disorder: evidence from preclinical models.Pharmacogenomics · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
Abstract
The A118G single-nucleotide polymorphism (SNP rs1799971) in the μ-opioid receptor gene, OPRM1, has been much studied in relation to alcohol use disorders. The reported effects of allelic variation at this SNP on alcohol-related behaviors, and on opioid receptor antagonist treatments, have been inconsistent. We investigated the pharmacogenetic interaction between A118G variation and the effects of two μ-opioid receptor antagonists in a clinical lab setting. Fifty-six overweight and moderate-heavy drinkers were prospectively stratified by genotype (29 AA homozygotes, 27 carriers of at least 1 G allele) in a double-blind placebo-controlled, three-period crossover design with naltrexone (NTX; 25 mg OD for 2 days, then 50 mg OD for 3 days) and GSK1521498 (10 mg OD for 5 days). The primary end point was regional brain activation by the contrast between alcohol and neutral tastes measured using functional magnetic resonance imaging (fMRI). Secondary end points included other fMRI contrasts, subjective responses to intravenous alcohol challenge, and food intake. GSK1521498 (but not NTX) significantly attenuated fMRI activation by appetitive tastes in the midbrain and amygdala. GSK1521498 (and NTX to a lesser extent) significantly affected self-reported responses to alcohol infusion. Both drugs reduced food intake. Across all end points, there was less robust evidence for significant effects of OPRM1 allelic variation, or for pharmacogenetic interactions between genotype and drug treatment. These results do not support strong modulatory effects of OPRM1 genetic variation on opioid receptor antagonist attenuation of alcohol- and food-related behaviors. However, they do support further investigation of GSK1521498 as a potential therapeutic for alcohol use and eating disorders.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.