Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis.
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.
Croxford
J Ludovic
JL
Department of Neuroinflammation, Institute of Neurology, University College London, London WC1N 1PJ, United Kingdom.
Pryce
Gareth
G
Jackson
Samuel J
SJ
Ledent
Catherine
C
Giovannoni
Gavin
G
Pertwee
Roger G
RG
Yamamura
Takashi
T
Baker
David
D
D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D009281:Naphthalenes / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology; D000077285:Rimonabant; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D048588:Benzoxazines; D002186:Cannabinoids; D007166:Immunosuppressive Agents; D009025:Morpholines; D009281:Naphthalenes; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC