Nalmefene is a µ- and δ-opioid receptor antagonist and a partial κ-opioid receptor agonist. The drug is suggested to reduce the craving for, and the consumption of alcohol effectively, also alleviating anxiety and anhedonia. The present fMRI study is the first to investigate the processing of emotions as a possible mechanism of action of nalmefene in humans. Fifteen non-treatment-seeking participants suffering from alcohol use disorder (AUD) (24-66 years; 5 females) finished this randomized, placebo controlled, double blind study. Following a cross over design, participants received either a single dose nalmefene or a placebo, with an interval of one week between sessions. Using fMRI, we investigated neural reactivity during the presentation of emotional faces picture sets. Additionally, we performed a visual dot-probe task to detect nalmefene's effects on attentional bias. We detected an increase in the response to emotional faces in the supramarginal gyrus, the angular gyrus as well as the putamen in the nalmefene vs. placebo condition. However, contradictory to our initial hypotheses, amygdala activation was not altered significantly in the placebo condition - a limitation, which might be associated with a lack of activation in the placebo condition maybe due to the small sample size. Attentional bias analyses revealed an interaction effect by trend, which was driven by a significant effect in a sub-analysis showing increased attentional shift towards happy compared to fearful facial expressions under nalmefene. Nalmefene increased brain activation in areas responsible for empathy, social cognition and behavior, which might help alleviating the reinforcing properties of alcohol.

中文翻译：

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纳美芬对酒精使用障碍情绪处理的影响——一项随机、对照 fMRI 研究

纳美芬是一种 µ- 和 δ-阿片受体拮抗剂和部分 κ-阿片受体激动剂。建议该药物可有效减少对酒精的渴望和饮酒，同时缓解焦虑和快感缺乏症。目前的 fMRI 研究是第一个研究情绪处理作为纳美芬在人类中的可能作用机制的研究。15 名患有酒精使用障碍 (AUD) 的非寻求治疗的参与者（24-66 岁；5 名女性）完成了这项随机、安慰剂对照、双盲研究。根据交叉设计，参与者接受单剂量纳美芬或安慰剂，两次疗程之间间隔一周。使用 fMRI，我们调查了情绪面孔图片集呈现期间的神经反应性。此外，我们执行了视觉点探针任务来检测纳美芬' s 对注意偏差的影响。我们检测到，在纳美芬与安慰剂条件下，边缘上回、角回以及壳核对情绪面孔的反应有所增加。然而，与我们最初的假设相反，杏仁核激活在安慰剂条件下没有显着改变 - 一个限制，这可能与安慰剂条件下缺乏激活有关，可能是由于样本量小。注意偏差分析揭示了趋势的交互作用，这是由子分析中的显着影响驱动的，该子分析显示与纳美芬下的恐惧面部表情相比，注意力转向快乐。纳美芬增加了负责移情、社会认知和行为的大脑区域的激活，这可能有助于减轻酒精的增强特性。