FAAH

Fatty acid amide hydrolase or FAAH is an integral membrane protein (IMP) that hydrolyzes bioactive amides including the endocannabinoid anandamide (an agonist of cannabinoid receptors and TRPV1 vanilloid receptors) and agonists of the peroxisome proliferator-activated receptors such as N-oleoylethanolamine and N-palmitoylethanolamine to free fatty acid and ethanolamine. It is also the primary terminator of the hypnotic lipid oleamide as well as the less well-characterized N-acyl taurines.

Due to its ability to regulate anandamide levels, it is currently viewed as an attractive drug target. A human mutation (proline 129 to threonine) has been associated with problem drug use. Additionally, genetic ablation or pharmacological inhibition of FAAH results in analgesia (lack of sensitivity to pain) in mice due, perhaps, to the effects of anandamide on cannabinoid receptors.

FAAH was cloned in 1996 by Ben Cravatt at The Scripps Research Institute where it continues to be intensively studied and characterized.

Inhibitors and assays
Both non-selective and selective inhibitors of the enzyme have been described. Examples of non-selective inhibitors include PMSF (phenylmethylsulfonylfluoride), MAFP, and ATMK (arachidonoyltrifluoromethylketone), while URB597 is widely regarded as the current 'gold standard' FAAH inhibitor. The enzyme is typically assayed making use of a radiolabelled anandamide substrate, which generates free labelled ethanolamine, although alternative spectrophotometric methods have also been described.