Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Heidelberg, Germany.
Psychopharmacology (Berl). 2021 Aug;238(8):2179-2189. doi: 10.1007/s00213-021-05842-7. Epub 2021 Apr 12.
Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available.
We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving.
Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level (M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues.
An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo.
In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
酒精使用障碍是一种常见且具有破坏性的精神疾病,目前仍缺乏令人满意的治疗方法。纳美芬作为一种阿片受体调节剂,通过减少酒精的(预期)奖赏作用和扩大治疗选择范围,在药理学上可以支持减少饮酒量。据推测,纳美芬通过对中脑边缘奖赏系统的间接调节起作用。到目前为止,关于纳美芬对神经元反应的成像研究结果很少。
我们测试了单次 18 毫克纳美芬对腹侧和背侧纹状体神经元线索反应性以及主观渴求的影响。
18 名非治疗寻求的酒精使用障碍参与者(67%为男性,平均年龄为 50.3 ± 13.9 岁),目前处于高风险饮酒水平(平均每天 76.9 ± 52 克纯酒精),在功能磁共振成像(fMRI)中使用线索反应性任务进行了双盲、安慰剂对照、交叉研究/设计。此外,在暴露于酒精线索前后评估了自我报告的渴求程度。
15 名参与者的 fMRI 数据的预先定义的感兴趣区域(ROI)分析显示,纳美芬降低了腹侧纹状体而非背侧纹状体的酒精线索反应性。此外,与安慰剂相比,在纳美芬下进行线索反应性任务后,主观渴求明显降低。
在本研究中,纳美芬降低了腹侧纹状体对酒精刺激的渴求反应和线索反应性,表明该药通过减弱神经酒精线索反应性,具有潜在的抗渴求作用。