Assessment of anandamide's pharmacological effects in mice deficient of both fatty acid amide hydrolase and cannabinoid CB1 receptors.

In the present study, we investigated whether anandamide produces its behavioral effects through a cannabinoid CB(1) receptor mechanism of action. The behavioral effects of anandamide were evaluated in mice that lacked both fatty acid amide hydrolase (FAAH) and cannabinoid CB(1) receptors (DKO) as compared to FAAH (-/-), cannabinoid CB(1) (-/-), and wild type mice. Anandamide produced analgesia, catalepsy, and hypothermia in FAAH (-/-) mice, but failed to elicit any of these effects in the other three genotypes. In contrast, anandamide decreased locomotor behavior regardless of genotype, suggesting the involvement of multiple mechanisms of action, including its products of degradation. These findings indicate that the cannabinoid CB(1) receptor is the predominant target mediating anandamide's behavioral effects.