Faah, or fatty acid amide hydrolase, is an intracellular enzyme responsible for the hydrolysis of the endogenous cannabinoid anandamide (AEA), terminating its biological effects [1]. It is a key player in the endocannabinoid system, which is involved in maintaining homeostasis by regulating immune response, energy metabolism, cognitive functions, and neuronal activity [2].

In a murine breast cancer model, inhibition of Faah increased cancer cell death in vitro, and in vivo Faah inhibition reduced breast cancer growth in immunodeficient mice, suggesting Faah inhibition could be a promising approach in cancer treatment [3]. Gene deletion of Faah in rodent models prevented stress-induced reductions in AEA levels, associated increases in basolateral amygdala dendritic hypertrophy, and anxiety-like behavior. Additionally, it facilitated long-term fear extinction and rescued deficient fear extinction [4].

In conclusion, Faah is essential for the inactivation of anandamide in the endocannabinoid system. Faah knockout (KO) or conditional knockout (CKO) mouse models have revealed its roles in stress-related responses and breast cancer, highlighting its potential as a therapeutic target for treating anxiety-related disorders and breast cancer [3,4].

References:

1. Bari, Monica, Feole, Monica, Fava, Marina, Maccarrone, Mauro. . Radiometric Assay of FAAH Activity. In Methods in molecular biology (Clifton, N.J.), 2576, 241-247. doi:10.1007/978-1-0716-2728-0_20. https://pubmed.ncbi.nlm.nih.gov/36152192/

2. Nicoara, Catalin, Fezza, Filomena, Maccarrone, Mauro. 2025. FAAH Modulators from Natural Sources: A Collection of New Potential Drugs. In Cells, 14, . doi:10.3390/cells14070551. https://pubmed.ncbi.nlm.nih.gov/40214504/

3. Tripathy, Mallika, Bui, Amy, Henderson, Jared, Louis Sam Titus, Anto Sam Crosslee, Mohan, Chandra. 2023. FAAH inhibition ameliorates breast cancer in a murine model. In Oncotarget, 14, 910-918. doi:10.18632/oncotarget.28534. https://pubmed.ncbi.nlm.nih.gov/37921652/

4. Gunduz-Cinar, Ozge, Hill, Matthew N, McEwen, Bruce S, Holmes, Andrew. 2013. Amygdala FAAH and anandamide: mediating protection and recovery from stress. In Trends in pharmacological sciences, 34, 637-44. doi:10.1016/j.tips.2013.08.008. https://pubmed.ncbi.nlm.nih.gov/24325918/