Cannabinoids and schizophrenia: where is the link?

Highlighting the association between schizophrenia and cannabis sativa and the endogenous cannabinoid receptor system, respectively, two opposite aspects are of major relevance. On the one hand, there is substantial evidence that cannabis has to be classified as an independent risk factor for psychosis that may lead to a worse outcome of the disease. This risk seems to be increased in genetically predisposed people and may depend on the amount of cannabis used. On the other hand, there are several lines of evidence suggesting that, at least in a subgroup of patients, alterations in the endocannabinoid system may contribute to the pathogenesis of schizophrenia, e.g., increased density of cannabinoid receptor type 1 (CB1) binding and increased levels of cerebrospinal fluid (CSF) anandamide. Accordingly, beside the „dopamine hypothesis“ of schizophrenia a „cannabinoid hypothesis“ has been suggested. Interestingly, there is a complex interaction between the dopaminergic and the cannabinoid receptor system. Thus, agents that interact with the cannabinoid receptor system such as the non-psychoactive cannabidiol (CBD) have been suggested for the treatment of psychosis.