Potential Role of Cannabinoid Type 2 Receptors in Neuropsychiatric and Neurodegenerative Disorders

The endocannabinoid system (ECS) is composed of the two canonical receptor subtypes; type-1 cannabinoid (CB1R) and type 2 receptor (CB2R), endocannabinoids (eCBs) and enzymes responsible for the synthesis and degradation of eCBs. Recently, with the identification of additional lipid mediators, enzymes and receptors, the expanded ECS called the endocannabinoidome (eCBome) has been identified and recognized. Activation of CB1R is associated with a plethora of physiological effects and some central nervous system (CNS) side effects, whereas, CB2R activation is devoid of such effects and hence CB2Rs might be utilized as potential new targets for the treatment of different disorders including neuropsychiatric disorders. Previous studies suggested that CB2Rs were absent in the brain and they were considered as peripheral receptors, however, recent studies confirmed the presence of CB2Rs in different brain regions. Several studies have now focused on the characterization of its physiological and pathological roles. Studies done on the role of CB2Rs as a therapeutic target for treating different disorders revealed important putative role of CB2R in neuropsychiatric disorders that requires further clinical validation. Here we provide current insights and knowledge on the potential role of targeting CB2Rs in neuropsychiatric and neurodegenerative disorders. Its non-psychoactive effect makes the CB2R a potential target for treating CNS disorders; however, a better understanding of the fundamental pharmacology of CB2R activation is essential for the design of novel therapeutic strategies.