FAAH-1

FAAH-1 (fatty acid amide hydrolase-1) is a membrane-associated serine hydrolase that terminates endocannabinoid signaling by hydrolyzing anandamide and other bioactive fatty acid amides, thereby regulating their tissue concentration and biological activity^[1][2]. Mechanistically, FAAH-1 functions as a major catabolic enzyme within the endocannabinoid pathway and controls the magnitude and duration of lipid-mediated signaling processes relevant to neuronal, inflammatory, and peripheral physiological responses^[1][3]. Experimental studies demonstrated that loss of FAAH activity enhances endogenous cannabinoid signaling and increases sensitivity to anandamide, establishing FAAH-1 as a critical regulator of endocannabinoid homeostasis in vivo^[4]. In disease-relevant and pharmacological models, modulation of FAAH activity has therefore been widely used to investigate pain, neuroinflammation, and other endocannabinoid-dependent biological processes^[3][4]. Compared with the related isoform FAAH-2, FAAH-1 exhibits substantially greater catalytic activity toward N-acyl ethanolamines, including anandamide, and toward N-acyl taurines, highlighting a distinct substrate preference within fatty acid amide metabolism^[5]. FAAH-1 and FAAH-2 also display overlapping but distinct tissue distributions, suggesting complementary roles in controlling fatty acid amide catabolism in primates^[5]. For experimental applications, selective FAAH inhibitors such as URB597, PF-3845, and related compounds are extensively employed to elevate endogenous fatty acid amide levels and probe endocannabinoid signaling mechanisms, making FAAH-1 a well-established pharmacological target for mechanistic research^[2][3].