Regulation of Endocannabinoids by Fatty Acid Amide Hydrolase

Three putative endogenous cannabinoids, anandamide, 2-AG, and NADA, appear to be susceptible to degradation by FAAH (Cravatt et al. 1996; Deutsch and Chin 1993; Di Marzo et al. 1998; Huang et al. 2002). Immunohistochemical studies show that FAAH is present in the ventral posterior lateral nucleus of the thalamus (Egertova et al. 1998, 2003; Tsou et al. 1998b), the termination zone of the spinothalamic tract. FAAH is also found in Lissauer's tract, which comprises primary afferent fibers entering the spinal cord, and in small neurons in the superficial dorsal horn, which is the termination zone of nociceptive primary afferents. These observations demonstrate that a mechanism capable of inactivating anandamide, 2-AG, and NADA is present in regions of the CNS related to nociceptive processing and thus suggest a role for these ligands in pain modulation. Of course, the presence of FAAH does not necessarily identify that cell as a site of synthesis of endocannabinoids, as FAAH is a catabolic enzyme and also metabolizes fatty acid amides that act through CBR-independent mechanisms.

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