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Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.

ABSTRACT: BACKGROUND:Genetic variation in the endogenous opioid system has been identified as 1 potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study was to test the pharmacogenetic effects of naltrexone on subjective response to alcohol and self-administration of alcohol in individuals of East Asian descent. We hypothesized that naltrexone, compared with placebo, would potentiate the aversive and sedative effects of alcohol and reduce alcohol self-administration to a greater extent in Asp40 carriers. METHODS:Participants (N = 77; Asn40Asn, n = 29; Asn40Asp, n = 34, and Asp40Asp, n = 14) completed 2 double-blinded and counterbalanced experimental sessions: one after taking naltrexone (50 mg/d) for 5 days and one after taking matched placebo for 5 days. In each experimental session, participants received a priming dose of intravenous alcohol up to the breath alcohol concentration target of 0.06 g/dl which was immediately followed by an alcohol self-administration period (1 hour). RESULTS:There were no pharmacogenetic effects observed for alcohol-induced stimulation, sedation, craving for alcohol, or alcohol self-administration in the laboratory. During the self-administration period, Asp40 carriers consumed fewer drinks and had a longer latency to first drink as compared to Asn40 homozygotes. CONCLUSIONS:These findings in East Asians add to the mixed literature on naltrexone pharmacogenetics from predominantly Caucasian samples and highlight the complexity of these effects and their overall limited replicability. It is plausible that a consistent pharmacogenetic effect in tightly controlled preclinical and experimental medicine models "fades" in more complex and heterogeneous settings and samples.

SUBMITTER: Ray LA

PROVIDER: S-EPMC6086578 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.

Ray Lara A LA Green ReJoyce R Roche Daniel J O DJO Bujarski Spencer S Hartwell Emily E EE Lim Aaron C AC Rohrbaugh Taylor T Ghahremani Dara D Hutchison Kent K Miotto Karen K

Alcoholism, clinical and experimental research 20180201 3

<h4>Background</h4>Genetic variation in the endogenous opioid system has been identified as 1 potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study was to test the pharmacogenetic effects of naltrexon ...[more]

PMID: 29265379

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Project description:Importance:Alcohol flushing syndrome (AFS, also known as Asian glow and Asian flush) affects 20% to 47% of East Asians and causes significant psychosocial distress. There are no approved treatments for this condition. Objective:To determine whether brimonidine gel, 0.33%, decreases facial erythema in patients with AFS after consumption of alcohol. Design, Setting, and Participants:In this randomized clinical trial, 20 healthy volunteers of East Asian descent with a self-reported history of AFS were recruited between April 2018 and March 2019. Interventions:Participants were randomized to application of brimonidine gel to either the left or right half of their face. Placebo control was applied to the opposite side. After 30 minutes, participants ingested alcohol. Main Outcomes and Measures:Outcomes were specified before data collection. The difference in erythema between the treated and placebo side of each participant's face was measured 60 minutes after drug application (primary outcome) and at 90 and 120 minutes after drug application (secondary outcomes). Participants were asked to rate their likelihood of using the medication again and their likelihood of recommending the medication to a friend on a scale of 0 to 10. Results:The mean (SD) age of the 20 individuals enrolled in the study was 30.5 (8.4) years, and there were 10 women (50%). There was a significant difference in erythema at 60 minutes after drug application as measured by the difference in Clinician Erythema Assessment score (2.1; 95% CI, 1.5-2.71; P?<?.001) and by the difference in Subject Self-Assessment score (1.7; 95% CI, 1.1- 2.3; P?<?.001). This effect persisted at 90 and 120 minutes. Individuals were likely to use the medication again (7.2; 95% CI, 6.0-8.3) and would also recommend it to a friend (7.6; 95% CI, 6.5-8.6). Conclusions and Relevance:This study demonstrates that brimonidine gel is effective in reducing the facial erythema of AFS. Patients with psychosocial distress due to AFS may benefit from treatment with brimonidine. Trial Registration:ClinicalTrials.gov identifier: NCT03497442.

Dataset Information

Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.

Publications

Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.

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