University of Washington School of Medicine, Seattle, Washington, USA.
Department of Psychiatry & Behavioral Sciences, and Radiology, University of Washington School of Medicine, Seattle, Washington, USA.
Cannabis Cannabinoid Res. 2021 Apr;6(2):105-118. doi: 10.1089/can.2020.0158. Epub 2021 Apr 5.
Recent research has suggested that chronic alcohol exposure induces changes in the endocannabinoid system within the central nervous system and therefore could be an attractive target for better understanding and treating alcohol use disorder (AUD). Much of this research has centered around the CB receptor and its endogenous partial agonist, the endocannabinoid anandamide, as the CB receptor is densely expressed in brain regions involved in development and maintenance of addictive behaviors. In addition, recent evidence has suggested that chronic alcohol exposure induces changes in the modulation of endocannabinoid concentration and suggests that these changes may contribute to the motivation to abuse alcohol. Therefore, we performed a systematic literature review to evaluate how fatty acid amide hydrolase (FAAH), an enzyme that degrades anandamide, relates to the characteristics and biology of AUD, as well as how modulating FAAH through pharmacologic inhibition or genetic manipulation affects outcomes related to alcohol use and consumption. A search strategy was developed using the terms "endocannabinoids" or "drug delivery systems" and "alcohol dependence" or "alcohol use disorder" or "alcoholism" and "Fatty Acid Amide Hydrolase" and "FAAH" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). We then used this search strategy on the electronic databases PubMed, Embase, and Web of Science. We found 224 records; after removing repeated records (37%), articles that did not fit the topic question (47%), or were not primary research (4%), we included 26 for qualitative synthesis (12%). The literature clearly suggests that FAAH has a role in the biology and characteristics of AUD. FAAH inhibition seems especially promising as a target for alcohol withdrawal as it may lead to a reduction in symptoms, including anxiety and a reduction of alcohol intake reinstatement. However, decreased FAAH may also lead to reduced sensitivity to alcohol along with increased preference and intake. Modulation of FAAH is promising for therapeutic intervention of AUD, but requires more research. Pre-clinical studies have indicated that FAAH inhibition may reduce withdrawal characteristics, but may also exacerbate other characteristics of AUD outside of that period.
最近的研究表明，慢性酒精暴露会导致中枢神经系统内的内源性大麻素系统发生变化，因此可能成为更好地理解和治疗酒精使用障碍（AUD）的有吸引力的靶点。这项研究的大部分集中在 CB 受体及其内源性部分激动剂，即内源性大麻素大麻素上，因为 CB 受体在参与成瘾行为的发展和维持的大脑区域中高度表达。此外，最近的证据表明，慢性酒精暴露会导致内源性大麻素浓度调节的变化，并表明这些变化可能导致滥用酒精的动机。因此，我们进行了系统的文献综述，以评估脂肪酸酰胺水解酶（FAAH），一种降解大麻素的酶，与 AUD 的特征和生物学有何关系，以及通过药理学抑制或遗传操作调节 FAAH 如何影响与酒精使用和消耗相关的结果。使用术语“内源性大麻素”或“药物传递系统”和“酒精依赖”或“酒精使用障碍”或“酒精中毒”以及“脂肪酸酰胺水解酶”和“FAAH”作为文本词和医学主题词（即 MeSH 和 EMTREE）制定了搜索策略。然后，我们在电子数据库 PubMed、Embase 和 Web of Science 上使用了此搜索策略。我们发现了 224 条记录；在去除重复记录（37%）、不符合主题问题的文章（47%）或不是主要研究（4%）后，我们纳入了 26 篇进行定性综合分析（12%）。文献清楚地表明，FAAH 在 AUD 的生物学和特征中起作用。FAAH 抑制似乎特别有希望作为酒精戒断的靶点，因为它可能导致症状减轻，包括焦虑和减少酒精摄入的恢复。然而，FAAH 的减少也可能导致对酒精的敏感性降低，同时增加对酒精的偏好和摄入。FAAH 的调节对于 AUD 的治疗干预有希望，但需要更多的研究。临床前研究表明，FAAH 抑制可能会降低戒断特征，但也可能在该时期之外加重 AUD 的其他特征。
