Anandamide hydrolysis: a new target for anti-anxiety drugs?
The major psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol, affects emotional states in humans and laboratory animals by activating brain cannabinoid receptors. A primary endogenous ligand of these receptors is anandamide, the amide of arachidonic acid with ethanolamine. Anandamide is released in selected regions of the brain and is deactivated through a two-step process consisting of transport into cells followed by intracellular hydrolysis. Pharmacological blockade of the enzyme fatty acid amide hydrolase (FAAH), which is responsible for intracellular anandamide degradation, produces anxiolytic-like effects in rats without causing the wide spectrum of behavioral responses typical of direct-acting cannabinoid agonists. These findings suggest that anandamide contributes to the regulation of emotion and anxiety, and that FAAH might be the target for a novel class of anxiolytic drugs.
Gaetani
Silvana
S
Department of Psychiatry, University of California, Irvine, CA 92697-4625, USA.
Cuomo
Vincenzo
V
Piomelli
Daniele
D
D000581:Amidohydrolases / Q000187:drug effects*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D014151:Anti-Anxiety Agents; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide