Immunomodulatory Role of CB2 Receptors in Emotional and Cognitive Disorders

Abstract

Emotional behavior, memory, and learning have been associated with alterations in the immune system in neuropsychiatric and neurodegenerative diseases. In recent years, several studies pointed out the involvement of the cannabinoid receptor 2 (CB2r) in the immune system and the regulation of inflammation. This receptor is widely distributed in different tissues and organs with higher expression in spleen and immune system cells. However, CB2r has also been detected in several brain areas and different brain cell types, such as neurons and glia. These findings suggest that CB2r may closely relate the immune system and the brain circuits regulating inflammation, mood, and cognitive functions. Therefore, we review the studies that may help elucidate the molecular bases of CB2r in regulating inflammation in different brain cells and its role in the pathophysiology of psychiatric and neurodegenerative disorders.

Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder

“…CB2 receptors have been found to be upregulated during inflammation in other brain-associated cells and have been shown to play a vital role in reducing depression in rodents (Morcuende et. al 2022 , Garcia-Gutierrezet. al 2018 , Onaivi et.…”

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

“…The pathological functions of the CB-2 receptor in inflammatory conditions (e.g., Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stress response, and depression) are under active investigation. 185 , 186 Inflammation is a driving factor of depression and could counter the effects of antidepressant therapies. 187 CB-2 receptor-overexpressing mice showed a significant reduction in depressive-related behaviors.…”

Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration

“…B cells and monocytes express higher levels of CB2 receptors than CD4+ (T helper) and CD8+ (T cytotoxic) T lymphocytes (Graham et al, 2010). Dendritic cells and macrophages may release endogenous cannabinoids in response to inflammatory stimuli, whereas activating CB2 receptors has profound anti-inflammatory effects by inhibiting T cell activation, M1 macrophage functions, immune cell proliferation and differentiation, and inducing apoptosis in both T and B cells (Turcotte et al, 2016;Ehrhart et al, 2005;Klein et al, 2004;Komorowska-Muller et al, 2020;Morcuende et al, 2022;Csoka et al, 2009;Lombard et al, 2007;Rieder et al, 2009;Maresz et al, 2007). When CB2 is activated, M1 macrophages acquire a M2 phenotype and produce more IL-10, an important CIRS cytokine (Correa et al, 2005;Klein et al, 1998).…”