The Cannabinoid CB1 Receptor in Schizophrenia

Converging lines of evidence from epidemiological, preclinical, and experimental studies indicate that the endo-cannabinoid system may be involved in the pathophysiology of schizophrenia and suggest that the cannabinoid CB1 receptor may be a potential therapeutic target. In view of this, we first provide an overview of the endocannabinoid system and systematically review the evidence for CB1 receptor alterations in animal models of schizophrenia and clinical studies in schizophrenia. MEDLINE, EMBASE, PsycArticles, and PsycINFO were systematically searched from inception until January 7, 2020. Of 1187 articles, 24 were included in the systematic review, including 8 preclinical studies measuring the CB1 receptor in the context of an established animal model of schizophrenia and 16 clinical studies investigating the CB1 receptor in schizophrenia. The majority of preclinical studies (6 of 8) have shown that the CB1 receptor is reduced in the context of animal models of schizophrenia. Moreover, the majority of in vivo clinical imaging studies that used arterial blood sampling to quantify the radiotracer kinetics (3 of 4) have shown reduced CB1 receptor availability in schizophrenia. However, mixed findings have been reported in ex vivo literature, including reports of no change in receptor levels (5 of 11), increased receptor levels (4 of 11), and decreased receptor levels (2 of 11). We review methodological reasons for these discrepancies and review how CB1 re-ceptor dysfunction may contribute to the pathophysiology of schizophrenia, drawing on the role of the receptor in regulating synaptic transmission and synaptic plasticity. We also discuss how the CB1 receptor may be a potential therapeutic target.