Role of the Endocannabinoid System in the Pathophysiology of Schizophrenia

Abstract

The endocannabinoid system (ECS) is a group of neuromodulatory lipids, enzymes, and receptors involved in numerous behavioral and physiological processes such as mood, memory, and appetite. Recently, longitudinal and postmortem studies have shown that the ECS might be involved in neuropsychiatric disorders like schizophrenia. However, despite the large amount of research, our knowledge of the ECS and its implication in this debilitating disorder is still largely limited. This review aims at providing a comprehensive overview of the current state of knowledge of the ECS in schizophrenia and presenting some potential antipsychotic compounds that modulate this system. Findings from animal and human studies, and their implications for pharmacotherapy, will be integrated and discussed in this paper. A closer look will be given at the roles of the cannabinoid receptors type 1 (CB₁) and type 2 (CB₂), as well as the endogenous ligand N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), in the development of psychotic and schizophrenia-like symptoms.

Keywords: Antipsychotics; Cannabinoid receptor; Cannabis; Endocannabinoid; Psychosis; Schizophrenia.