Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists

Summary

Delta(9)-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, can cause psychomotor effects, psychotic reactions, and cognitive impairment similar to schizophrenia. These effects can be reduced by two other cannabinoids: cannabidiol (CBD) and SR141716. CBD, the second most abundant cannabis constituent, weakly antagonizes the CB(1) receptor, inhibits anandamide reuptake and hydrolysis, and has neuroprotective antioxidant activity. SR141716 is a potent and selective CB(1) receptor antagonist. Both can reverse many effects of CB(1) receptor agonists, suggesting antipsychotic properties. Experimental studies in animals, healthy volunteers, and schizophrenic patients support this, with a pharmacological profile similar to atypical antipsychotic drugs. This review presents preclinical and clinical studies on the potential antipsychotic effects of CBD and SR141716.

Study at a glance

Abstract

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB(1)) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Delta(9)-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB(1) receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB(1) receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB(1) receptor antagonist. Since both CBD and SR141716 can reverse many of the biochemical, physiological and behavioural effects of CB(1) receptor agonists, it has been proposed that both CBD and SR141716 have antipsychotic properties. Various experimental studies in animals, healthy human volunteers, and schizophrenic patients support this notion. Moreover, recent studies suggest that cannabinoids such as CBD and SR141716 have a pharmacological profile similar to that of atypical antipsychotic drugs. In this review, both preclinical and clinical studies investigating the potential antipsychotic effects of both CBD and SR141716 are presented together with the possible underlying mechanisms of action.