Fatty acid amide hydrolase 1 (FAAH1) (FAAH1)

Fatty acid amide hydrolase 1 (FAAH1) is a membrane-bound serine hydrolase enzyme that serves as the primary catabolic regulator of the endocannabinoid anandamide (N-arachidonoylethanolamine) (UniProt P43088). By degrading anandamide into arachidonic acid and ethanolamine, FAAH1 effectively terminates its signaling at cannabinoid receptors (CB1 and CB2) and other targets like TRPV1 (PubMed: 11322990). Pharmacological inhibition of FAAH1 elevates endogenous anandamide levels, providing a strategy to enhance endocannabinoid signaling on demand in a more localized and physiological manner than direct CB receptor agonists (PubMed: 27016595). This mechanism has been extensively explored for the treatment of chronic pain, anxiety, and inflammatory conditions, as it avoids the psychotropic side effects typically associated with direct CB1 activation (PubMed: 15652448). Despite its therapeutic promise, the field faced a significant setback with the BIA 10-2474 clinical trial, though subsequent research suggests the toxicity was due to off-target activity rather than FAAH1 inhibition itself (PubMed: 28593957).

Other names

FAAHFAAH-1Anandamide amidohydrolaseOleamide hydrolase

Inhibition of the FAAH1 enzyme prevents the hydrolysis of the endocannabinoid anandamide, thereby increasing its levels and prolonging its activation of cannabinoid receptors (CB1 and CB2) and other targets like TRPV1 (PubMed: 11322990).