Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
Neuropsychopharmacology. 2017 Dec;42(13):2640-2653. doi: 10.1038/npp.2017.74. Epub 2017 Apr 14.
Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs), but it is not effective for everyone. Variability in its effects on reward-related brain activation, genetic variation, and/or cigarette smoking may account for this mixed response profile. This randomized clinical trial tested the effects of naltrexone on drinking and alcohol cue-elicited brain activation, evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and explored whether the effects of medication on cue-elicited activation predicted subsequent drinking. One hundred and fifty-two treatment-seeking individuals with alcohol dependence, half preselected to carry at least one A118G G (Asp) allele, were randomized to naltrexone (50 mg) or placebo for 16 weeks and administered an fMRI alcohol cue reactivity task at baseline and after 2 weeks of treatment. Naltrexone, relative to placebo, significantly reduced alcohol cue-elicited activation of the right ventral striatum (VS) between baseline and week 2 and reduced heavy drinking over 16 weeks. OPRM1 genotype did not significantly moderate these effects, but G-allele carriers who received naltrexone had an accelerated return to heavy drinking after medication was stopped. Smoking moderated the effects of medication on drinking, such that naltrexone was superior to placebo only among smokers. The degree of reduction in right VS activation between scans interacted with medication in predicting subsequent drinking, such that individuals with greater reduction in activation who received naltrexone, but not placebo, experienced the least heavy drinking during the following 14 weeks. These data replicate previous findings that naltrexone reduces heavy drinking and reward-related brain activation among treatment-seeking individuals with AUDs, and indicate that smoking and the magnitude of reduction in cue-elicited brain activation may predict treatment response.
纳曲酮可减少患有酒精使用障碍（AUD）的个体的饮酒量，但并非对所有人都有效。其对与奖励相关的大脑激活、遗传变异和/或吸烟的影响的变异性可能解释了这种混合反应模式。这项随机临床试验测试了纳曲酮对饮酒和酒精线索诱发的大脑激活的影响，评估了 OPRM1 A118G 基因型或吸烟是否调节了这些影响，并探讨了药物对线索诱发的激活的影响是否预测随后的饮酒。152 名寻求治疗的酒精依赖患者，其中一半预先选择携带至少一个 A118G G（天冬氨酸）等位基因，被随机分配接受纳曲酮（50mg）或安慰剂治疗 16 周，并在基线和治疗 2 周后进行 fMRI 酒精线索反应性任务。与安慰剂相比，纳曲酮显著降低了基线至第 2 周期间右侧腹侧纹状体（VS）对酒精线索的激活，并且减少了 16 周内的重度饮酒。OPRM1 基因型并未显著调节这些影响，但接受纳曲酮治疗的 G 等位基因携带者在停药后迅速恢复重度饮酒。吸烟调节了药物对饮酒的影响，因此纳曲酮仅在吸烟者中优于安慰剂。扫描之间右侧 VS 激活的减少程度与药物相互作用，预测了随后的饮酒，即接受纳曲酮而不是安慰剂治疗的个体，在接下来的 14 周内，饮酒量最少。这些数据复制了先前的发现，即纳曲酮可减少寻求治疗的 AUD 患者的重度饮酒和与奖励相关的大脑激活，并表明吸烟和线索诱发的大脑激活减少的幅度可能预测治疗反应。
