The Effect of Cannabidiol on Psychosis-like Behaviour Induced by Methamphetamine and MK-801 in Mice: A Negative Report

Background: Cannabis is a widely used illicit substance but may also have medicinal properties. Cannabidiol (CBD), one of the main compounds of interest in the cannabis plant, has been suggested to have beneficial effects in various psychiatric disorders including anxiety and psychosis. Drug-induced locomotor hyperactivity is a commonly used animal model of psychosis-like behaviour and to show antipsychotic drug action. Several genetic and developmental animal models of psychosis show differences in locomotor hyperactivity. The aim of the present study was to investigate the effect of pretreatment with CBD on psychosis-like behaviour in mice. Methods: The animals underwent 5 sessions of locomotor activity testing each, with 3–4 days between tests to allow washout of acute drug challenge. Groups of mice (n = 8 male mice and n = 8 female mice combined) were pretreated with CBD (10 mg/kg) or its vehicle, followed 1 h later with either saline, the dopamine releaser, methamphetamine (1 or 3 mg/kg), or the NMDA receptor antagonist, MK-801 (0.1 or 0.25 mg/kg). Results: There was no significant effect of CBD on its own on locomotor activity. Pretreatment with CBD had no effect on the hyperlocomotion induced by either dose of methamphetamine. There was also no effect of CBD on MK-801 induced hyperlocomotion following the 0.25 mg/kg dose, while 0.1 mg/kg MK-801 did not induce hyperactivity. Conclusions: These results do not support an antipsychotic action of CBD