Fatty acid amide hydrolase (FAAH) (FAAH)

Fatty acid amide hydrolase (FAAH) is a membrane-bound serine hydrolase enzyme that plays a pivotal role in the termination of signaling by fatty acid amides, most notably the sleep-inducing lipid oleamide and the endocannabinoid anandamide (UniProt P97612). By catalyzing the hydrolysis of oleamide into oleic acid and ammonia, FAAH acts as a key regulator of the oleamide pathway, which is essential for maintaining normal sleep-wake cycles and modulating pain perception (PubMed 8620640). In the context of disease, dysregulation of FAAH activity is linked to chronic pain, anxiety, and sleep disorders, making it a highly attractive therapeutic target for drug development (PubMed 27099138). Pharmacological inhibition of FAAH increases the local concentrations of its substrates, thereby enhancing their beneficial effects on cannabinoid and vanilloid receptors without the side effects typically associated with direct agonists (PubMed 21865511). Several small-molecule inhibitors, such as PF-04457845, have reached clinical trials for pain and post-traumatic stress disorder, although the field faced significant scrutiny following the severe adverse events associated with the non-selective inhibitor BIA 10-2474 (PubMed 28591538). Current research continues to focus on highly selective FAAH inhibitors to harness the therapeutic potential of the oleamide and endocannabinoid pathways safely.

Other names

Oleamide hydrolaseAnandamide amidohydrolaseFAAH-1Fatty-acid amide hydrolase 1

Inhibition of the FAAH enzyme to prevent the hydrolysis of fatty acid amides, thereby increasing the endogenous levels of signaling lipids like anandamide and oleamide.