Fatty acid amide hydrolase (FAAH) belongs to the serine hydrolase family of enzymes. The identification of this enzyme was led by the discovery and characterization of fatty acid amides, including anandamide and oleamide, as a fundamental class of endogenous signaling molecules. FAAH serves as the major metabolic regulator of many of the endogenous fatty acid amides, exhibiting a distribution consistent with its role in regulating their effects at their released sites of action.
A number of research studies have demonstrated that genetic and pharmacological inactivation of FAAH produces analgesic, anti-inflammatory, anxiolytic, neurogenic, neuropsychiatric, and anti-depressant phenotypes without showing the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target.
On the contrary, the pipeline of FAAH inhibitors is not very robust with only 5+ active products and no late-stage (Phase III) product. Janssen and Spring Works Therapeutics are among the key players developing drugs in the Phase II stage. However, in 2016, J&J voluntarily suspended the development of JNJ-42165279 in the wake of a French clinical trial that caused death of one volunteer. Later, the company initiated the Phase II trial in the United States, Romania, Europe, Australia, Canada, and Russia for Anxiety disorders. On the other hand, PF-04457845 is being evaluated for a number of indications such as Osteoarthritis, Post-Traumatic Stress Disorder, Cannabis use disorder, acute/chronic pain, Tourette syndrome, and fear.
In addition to this, quite a few top-ranking drug development companies such as Sanofi and Vernalis abandoned their FAAH programs for strategic reasons and inefficacy respectively.
Although, therapeutic development of FAAH inhibitors is not the current market focus, the future scope of the enzyme inhibitors suggests that it can be utilized for various indications involving central nervous system due to its wide range of mechanism of action.