Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Department of Urology, Faculty of Medicine Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
Cannabis Cannabinoid Res. 2023 Feb;8(1):56-76. doi: 10.1089/can.2021.0237. Epub 2022 Jul 27.
Fatty acid amide hydrolase (FAAH) is one of the main terminating enzymes of the endocannabinoid system (ECS). Since being discovered in 1996, the modulation of FAAH has been viewed as a compelling alternative strategy to obtain the beneficial effect of the ECS. With a considerable amount of FAAH-related publication over time, the next step would be to comprehend the proximity of this evidence for clinical application. This review intends to highlight the rationale of FAAH modulation and provide the latest evidence from clinical studies. Publication searches were conducted to gather information focused on FAAH-related clinical evidence with an extension to the experimental research to understand the biological plausibility. The subtopics were selected to be multidisciplinary to offer more perspective on the current state of the arts. Experimental and clinical studies have demonstrated that FAAH was highly expressed not only in the central nervous system but also in the peripheral tissues. As the key regulator of endocannabinoid signaling, it would appear that FAAH plays a role in the modulation of mood and emotional response, reward system, pain perception, energy metabolism and appetite regulation, inflammation, and other biological processes. Genetic variants may be associated with some conditions such as substance/alcohol use disorders, obesity, and eating disorder. The advancement of functional neuroimaging has enabled the evaluation of the neurochemistry of FAAH in brain tissues and this can be incorporated into clinical trials. Intriguingly, the application of FAAH inhibitors in clinical trials seems to provide less striking results in comparison with the animal models, although some potential still can be seen. Modulation of FAAH has an immense potential to be a new therapeutic candidate for several disorders. Further exploration, however, is still needed to ensure who is the best candidate for the treatment strategy.
脂肪酸酰胺水解酶（FAAH）是内源性大麻素系统（ECS）的主要终止酶之一。自 1996 年被发现以来，FAAH 的调节被视为获得 ECS 有益效果的一种有吸引力的替代策略。随着时间的推移，出现了相当数量的 FAAH 相关出版物，下一步将是理解这些证据对临床应用的接近程度。 本综述旨在强调 FAAH 调节的基本原理，并提供来自临床研究的最新证据。 进行了出版物搜索，以收集集中在 FAAH 相关临床证据的信息，并扩展到实验研究，以了解生物学的合理性。选择了亚主题以使其具有多学科性，以便更全面地了解当前的艺术状态。 实验和临床研究表明，FAAH 不仅在中枢神经系统中高度表达，而且在外周组织中也高度表达。作为内源性大麻素信号的关键调节剂，FAAH 似乎在调节情绪和情绪反应、奖励系统、疼痛感知、能量代谢和食欲调节、炎症和其他生物过程中发挥作用。遗传变异可能与某些疾病有关，如物质/酒精使用障碍、肥胖和饮食失调。功能神经影像学的进步使得能够评估脑组织中 FAAH 的神经化学，这可以纳入临床试验。有趣的是，与动物模型相比，FAAH 抑制剂在临床试验中的应用似乎没有那么显著的效果，尽管仍然可以看到一些潜力。 FAAH 的调节有可能成为几种疾病的新治疗候选药物。然而，仍需要进一步探索，以确保谁是治疗策略的最佳候选者。
