Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis
Proceedings of the National Academy of Sciences December 13, 2005 Gabriella Gobbi, Francis Rodriguez Bambico, Regina A. Mangieri et al. 675 citations
Inhibiting the enzyme fatty-acid amide hydrolase (FAAH) with URB597, which prevents the breakdown of the endocannabinoid anandamide, produces antidepressant-like effects in mice and rats. URB597 reduced immobility in the tail-suspension and forced-swim tests, and increased firing of serotonin and norepinephrine neurons in brain regions linked to mood. These effects required CB1 receptor activation and were accompanied by higher brain anandamide levels. Unlike direct THC-like drugs, URB597 showed no rewarding or abuse-related effects. The findings suggest FAAH inhibition as a potential target for antidepressant drugs without the psychotropic side effects of cannabis.