Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis

J Neuroimmunol. 2008 Jan;193(1-2):120-9. doi: 10.1016/j.jneuroim.2007.10.024. Epub 2007 Nov 26.

Abstract

Cannabinoids may exhibit symptom control in multiple sclerosis (MS). We show here that cannabinoid receptor (CBR) agonists can also be immunosuppressive and neuroprotective in models of MS. Immunosuppression was associated with reduced: myelin-specific T cell responses; central nervous system infiltration and reduced clinical disease. This was found to be largely CB(1)R-dependent and only occurred at doses that induced significant cannabimimetic effects that would not be achieved clinically. Lower, non-immunosuppressive doses of cannabinoids however, slowed the accumulation of nerve loss and disability, despite failing to inhibit relapses. This further highlights the neuroprotective potential of cannabinoids to slow the progression of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines / pharmacology
  • Cannabinoids / pharmacology*
  • Cannabinoids / therapeutic use
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Naphthalenes / pharmacology
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / physiology
  • Receptor, Cannabinoid, CB2 / physiology
  • Rimonabant
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Benzoxazines
  • Cannabinoids
  • Immunosuppressive Agents
  • Morpholines
  • Naphthalenes
  • Neuroprotective Agents
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Rimonabant
  • 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC