FAAH is an integral membrane hydrolase with a single N-terminal transmembrane domain. In vitro, FAAH has esterase and amidase activity.^[5] In vivo, FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of the FAAs include:

• Anandamide (N-arachidonoylethanolamine), an endocannabinoid^[6]
• 2-arachidonoylglycerol (2-AG), an endocannabinoid.^[7]
• Other N-acylethanolamines, such as N-oleoylethanolamine and N-palmitoylethanolamine^[8]
• The sleep-inducing lipid oleamide^[9]
• The N-acyltaurines, which are agonists of the transient receptor potential (TRP) family of calcium channels.^[10]

FAAH knockout mice display highly elevated (>15-fold) levels of N-acylethanolamines and N-acyltaurines in various tissues. Because of their significantly elevated anandamide levels, FAAH KOs have an analgesic phenotype, showing reduced pain sensation in the hot plate test, the formalin test, and the tail flick test.^[11] Finally, because of their impaired ability to degrade anandamide, FAAH KOs also display supersensitivity to exogenous anandamide, a cannabinoid receptor (CB) agonist.^[6]

Due to the ability of FAAH to regulate nociception, it is currently viewed as an attractive drug target for the treatment of pain.^[12][13][14]

A mutation in FAAH was initially provisionally linked to drug abuse and dependence but this was not borne out in subsequent studies.^[15]

Studies in cells and animals and genetic studies in humans have shown that inhibiting FAAH may be a useful strategy to treat anxiety disorders.^[15][16][17]

Based on the hydrolytic mechanism of fatty acid amide hydrolase, a large number of irreversible and reversible inhibitors of this enzyme have been developed.^{[18][19][20][21][22][23][24][25]}

Some of the more significant compounds are listed below;

Structural and conformational properties that contribute to enzyme inhibition and substrate binding imply an extended bound conformation, and a role for the presence, position, and stereochemistry of a delta cis double bond.^[41]

The enzyme is typically assayed making use of a radiolabelled anandamide substrate, which generates free labelled ethanolamine, although alternative LC-MS methods have also been described.^[42][43]

The first crystal structure of FAAH was published in 2002 (PDB code 1MT5).^[4] Structures of FAAH with drug-like ligands were first reported in 2008, and include non-covalent inhibitor complexes and covalent adducts.^[44]

• Endocannabinoid enhancer
• Endocannabinoid reuptake inhibitor
• Monoacylglycerol lipase
• FAAH2

• fatty-acid+amide+hydrolase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Proteopedia FAAH entry – interactive structure (JMOL) of inhibitor-bound FAAH