Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors

• DOI: 10.1016/j.nbd.2013.06.016
• Publication Date: 2013-07-11T18:01:21Z
• Authors: M. Mecha; A. Feliú; P.M. Iñigo; L. Mestre; F.J. Carrillo-Sal...; C. Guaza
• Keywords: 0301 basic medicine; Adenosine; Interleukin-1beta; experimental autoimmune encephalomyelitis; TMEV-IDD; tetrahydrocannabinol; Mice; Cannabidiol; Chemokine CCL5; Cells, Cultured; Chemokine CCL2; Theiler's murine encephalomyelitis virus-induced demyelinating disease; VCAM-1; CCL5; chemokine ligand 2; EAE; Theiler's murine encephalomyelitis virus; Triazines; chemokine ligand 5; Brain; 3. Good health; Neurology; Blood brain barrier; CBD; Microglia; CNS; Chemokines; CCL2; RC321-571; very late antigen-4; THC; Multiple Sclerosis; Receptor, Adenosine A2A; chemokine receptor 2; VLA-4; Vascular Cell Adhesion Molecule-1; Neurosciences. Biological psychiatry. Neuropsychiatry; Motor Activity; Multiple sclerosis; 03 medical and health sciences; Cardiovirus Infections; Cell Adhesion; Animals; Inflammation; Endothelial Cells; MS; Triazoles; central nervous system; Disease Models, Animal; CCR2; Infiltrates; BBB

Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component.