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Anandamide hydrolysis: a new target for anti-anxiety drugs?
by
Gaetani S, Cuomo V, Piomelli D.
ABSTRACT
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.
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