Abstract
The major psychoactive constituent of cannabis, Δ 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.
Highlights
The major psychoactive constituent of cannabis, D9-tetrahydrocannabinol, affects emotional states in humans and laboratory animals by activating brain cannabinoid receptors
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
Mutant mice lacking the gene encoding FAAH (Faah) cannot metabolize anandamide and show various signs of an exaggerated anandamide tone [29]. These findings suggest that selective inhibitors of intracellular FAAH activity could enhance the actions of anandamide in brain areas where synthesis and release of this compound occur under physiological conditions
Summary
The major psychoactive constituent of cannabis, D9-tetrahydrocannabinol, affects emotional states in humans and laboratory animals by activating brain cannabinoid receptors. 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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