Fatty Acid Amide Hydrolase: An Integrative Clinical Perspective

Introduction: 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. Objective: This review intends to highlight the rationale of FAAH modulation and provide the latest evidence from clinical studies. Methods: 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. Discussion: 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. Conclusion: 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.