Cannabidiol Provides Long-Lasting Protection Against the Deleterious Effects of Inflammation in a Viral Model of Multiple Sclerosis: A Role for A2A Receptors

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Cannabidiol / therapeutic use*
  • Cardiovirus Infections / complications
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / virology
  • Inflammation / drug therapy*
  • Inflammation / etiology*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Mice
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / etiology
  • Multiple Sclerosis* / virology
  • Receptor, Adenosine A2A / genetics
  • Receptor, Adenosine A2A / metabolism*
  • Triazines / pharmacology
  • Triazoles / pharmacology
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Chemokine CCL2
  • Chemokine CCL5
  • Interleukin-1beta
  • Receptor, Adenosine A2A
  • Triazines
  • Triazoles
  • Vascular Cell Adhesion Molecule-1
  • ZM 241385
  • Cannabidiol