title: Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors.
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.
authors.affiliation: Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mecha
authors.forename: A
authors.initials: A
authors.lastname: Feliú
authors.forename: P M
authors.initials: PM
authors.lastname: Iñigo
authors.forename: L
authors.initials: L
authors.lastname: Mestre
authors.forename: F J
authors.initials: FJ
authors.lastname: Carrillo-Salinas
authors.forename: C
authors.initials: C
authors.lastname: Guaza
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002185:Cannabidiol / Q000627:therapeutic use*; D018188:Cardiovirus Infections / Q000150:complications; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000821:virology; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009103:Multiple Sclerosis / Q000150:complications / Q000209:etiology / Q000821:virology; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D053583:Interleukin-1beta; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; D019010:Vascular Cell Adhesion Molecule-1; C097270:ZM 241385; D002185:Cannabidiol
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