The endocannabinoid enzyme, fatty acid amide hydrolase (FAAH), has been proposed as a therapeutic target for alcohol use disorder (AUD) and co-morbid psychiatric illnesses. Investigating this target in the living human brain and its relationship to clinical outcome is a critical step of informed drug development. Our objective was to establish whether brain FAAH levels are low in individuals with AUD and related to drinking behavior. In this pilot study, treatment-seeking patients with AUD completed two PET scans with the FAAH radiotracer [C-11]CURB after 3-7 days (n = 14) and 2-4 weeks (n = 9) of monitored abstinence. Healthy controls (n = 25) completed one scan. FAAH genetic polymorphism (rs324420) and blood concentrations of anandamide and other N-acylethanolamines metabolized by FAAH were determined and AUD symptoms assessed. In AUD, brain FAAH levels were globally lower than controls during early abstinence (F(1,36) = 5.447; p = 0.025)) and FAAH substrates (anandamide, oleoylethanolamide, and N-docosahexaenoylethanolamide) were significantly elevated (30-67%). No significant differences in FAAH or FAAH substrates were noted after 2-4 weeks abstinence. FAAH levels negatively correlated with drinks per week (r = -0.57, p = 0.032) and plasma concentrations of the three FAAH substrates (r > 0.57; p < 0.04)). Our findings suggest that early abstinence from alcohol in AUD is associated with transiently low brain FAAH levels, which are inversely related to heavier alcohol use and elevated plasma levels of FAAH substrates. Whether low FAAH is an adaptive beneficial response to chronic alcohol is unknown. Therapeutic strategies focusing on FAAH inhibition should consider the possibility that low FAAH during early abstinence may be related to drinking.

中文翻译：

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寻求治疗的酒精使用障碍患者的下脑脂肪酸酰胺水解酶：[C-11] CURB的正电子发射断层扫描研究。

内源性大麻素酶，脂肪酸酰胺水解酶（FAAH），已被提议作为酒精使用障碍（AUD）和合并症的精神疾病的治疗靶标。在人类大脑中研究该靶标及其与临床结果的关系是知情药物开发的关键步骤。我们的目标是确定患有AUD的人的大脑FAAH水平是否较低，并且与饮酒行为有关。在这项前瞻性研究中，寻求治疗的AUD患者在3-7天（n = 14）和2-4周（n = 9）禁欲后，用FAAH放射性示踪剂[C-11] CURB完成了两次PET扫描。健康对照（n = 25）完成了一次扫描。确定FAAH遗传多态性（rs324420）以及被FAAH代谢的anandamide和其他N-酰基乙醇胺的血药浓度，并评估AUD症状。在澳元中 在早期禁欲期间，大脑的FAAH水平总体低于对照组（F（1,36）= 5.447; p = 0.025），而FAAH底物（花生四烯酸，油酰乙醇酰胺和N-二十二碳六烯酰基乙醇酰胺）显着升高（30-67％）。禁食2-4周后，未观察到FAAH或FAAH底物的显着差异。FAAH水平与每周饮酒（r = -0.57，p = 0.032）和三种FAAH底物的血浆浓度呈负相关（r> 0.57; p <0.04））。我们的研究结果表明，AUD戒酒的早期原因与短暂的大脑FAAH水平低相关，而后者与大量饮酒和FAAH底物血浆水平升高呈负相关。低FAAH是否是对慢性酒精的适应性有益反应尚不清楚。