Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response - A double-blind placebo-controlled study
Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response - A double-blind placebo-controlled study
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DOI：
10.1001/archpsyc.64.9.1069
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发表时间：
2007-09-01
影响因子：
--
通讯作者：
Hutchison, Kent E.
中科院分区：
文献类型：
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作者：
Ray, Lara A.;Hutchison, Kent E.
内容：临床试验表明，纳洛酮作为酒精中毒的药物治疗具有适度的效果，最近的一项研究表明，这种效果可能会受到μ阿片受体基因（OPRM 1）变异的影响。然而，纳洛酮可能作为OPRM 1基因型的函数而具有差异有效性的机制尚不清楚。目的：（1）复制和扩展OPRM 1基因的A118 G单核苷酸多态性（SNP）与酒精敏感性之间的关联，（2）检查纳洛酮对酒精敏感性的影响，（3）测试OPRM 1基因的A118 G SNP作为纳曲酮对酒精敏感性影响的调节剂。设计：纳曲酮的受试者内、双盲、安慰剂对照实验室试验。设置：参与者从社区招募。参与者：非寻求治疗的重度饮酒者被纳入本研究。干预：服用纳曲酮（50 mg）或安慰剂后，参与者完成了一次静脉酒精挑战，在基线和3个目标呼气酒精浓度（0.02，0.04和0.06 mg/L）中的每一个进行评估。主要结果测量：双相酒精效应量表，酒精冲动问卷，情绪状态的配置文件，和酒精等级Scale.Results：个人至少有1个副本的G等位基因报告低酒精渴望和较高的酒精诱导的“高”在呼吸酒精浓度上升。纳洛酮被发现可以减弱酒精对刺激、积极情绪、渴望和享受的影响。纳曲酮钝化酒精引起的高的影响是较强的个人与G allele.Conclusion：这项研究的进展纳曲酮的作用机制和遗传调节剂的反应，这种药物治疗的知识。
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.