Department of Neurology, University of California, San Francisco, CA, USA.
Department of Neurology, VA Northern California Health Care System, Mather, CA, USA.
Psychopharmacology (Berl). 2020 Oct;237(10):3139-3148. doi: 10.1007/s00213-020-05599-5. Epub 2020 Jul 2.
Individuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD.
To determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks.
We used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD.
Tolcapone significantly reduced self-reported alcohol consumption (t (54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r (45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo.
These data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.
ClinicalTrials.gov Identifier: NCT02740582.
患有酒精使用障碍（AUD）的个体表现出决策困难和冲动，这可能与额叶皮质功能受损有关。增强额叶多巴胺能的治疗方法可以降低冲动性，从而减少 AUD 个体的饮酒量。
确定儿茶酚-O-甲基转移酶（COMT）抑制剂托卡朋是否可以减少 AUD 个体的饮酒量，以及这种减少是否与托卡朋引起的实验室决策任务变化相关。
我们使用每日自我报告和一项新的团体实验室棒任务来评估随机双盲交叉给予托卡朋（100mg TID，持续 5 天）对 55 名非治疗寻求者 AUD 个体的饮酒量和实验室任务评估冲动性的影响。
托卡朋显著减少了自我报告的饮酒量（t (54) = 2.05，p = 0.045）。托卡朋对饮酒的影响与冲动性决策的变化显著相关，即托卡朋治疗后冲动性选择减少最大的个体报告饮酒量也减少最大（r (45) = 0.40，p = 0.0053）。我们没有看到托卡朋对实验室棒消耗的影响。不良事件（AE）报告较低，托卡朋与安慰剂相比，AE 的频率或严重程度无显著差异。
这些数据表明，COMT 抑制剂，如托卡朋，可能是 AUD 的有用治疗方法。
ClinicalTrials.gov 标识符：NCT02740582。
