Role of cannabinoid receptors in anxiety disorders

Abstract

Cannabinoid agents modulate anxiety, although their effects vary and depend on regional endogenous tone, basal anxiety levels, environmental context, species differences, type of anxiety, prior exposure, and dose. Cannabinoid receptors are densely located in brain areas that are involved in the regulation of emotional states and induce neurochemical responses that are congruent with anxiolyt ic/anxiogenic effects. The effects on emotion mediated by cannabinoid compounds are believed to be due to a regulation of activity at the cannabinoid CB1 receptors although there is some limited evidence implicating the cannabinoid CB2 and a putative novel cannabinoid receptor (GPR55?) in some of the observed emotional responses. Effects on emotion are likely the result of a net effect of the summated neurochemical responses. Compounds that indirectly regulate activity at the cannabinoid receptors more consistently reduce anxiety both in preclinical and clinical models. Consequently, these compounds may be the focus of future pharmaceutical development of anxiolytic compounds.