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Neurobiol Dis. 2013 Nov;59:141-50. doi: 10.1016/j.nbd.2013.06.016. Epub 2013 Jul 11.

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

Author information

1
Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, Spain.

Abstract

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.

KEYWORDS:

Adenosine; BBB; CBD; CCL2; CCL5; CCR2; CNS; Cannabidiol; Chemokines; EAE; Infiltrates; Inflammation; MS; Microglia; Multiple sclerosis; THC; TMEV-IDD; Theiler's murine encephalomyelitis virus; Theiler's murine encephalomyelitis virus-induced demyelinating disease; VCAM-1; VLA-4; blood brain barrier; cannabidiol; central nervous system; chemokine ligand 2; chemokine ligand 5; chemokine receptor 2; experimental autoimmune encephalomyelitis; multiple sclerosis; tetrahydrocannabinol; very late antigen-4

PMID:
23851307
DOI:
10.1016/j.nbd.2013.06.016
[Indexed for MEDLINE]
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