Several lines of experimental and clinical evidence point to a close relationship between cannabis, the endogenous cannabinoid
system, and schizophrenia. A variety of animal and human studies found a dysregulation of endocannabinoid signalling in psychosis.
Elevated anandamide levels in schizophrenia patients that are negatively correlated with psychotic symptomatology indicate a protective
role, whereas 2-arachidonoylglycerol appears to counteract psychosis-related cognitive impairments. Thus, pharmacological manipulation
of the endogenous cannabinoid system might be associated with potential antipsychotic properties. In the present systematic review,
both preclinical studies using different animal models of psychosis as well as clinical trials investigating the antipsychotic effects of both
cannabidiol and rimonabant are presented together with the possible underlying mechanisms of action. The results predominantly confirm
the hypothesis of an antipsychotic activity of both cannabinoids. In comparison, cannabidiol appears to be superior to rimonabant
with a pharmacological profile similar to atypical antipsychotic drugs.