Cannabinoids control spasticity and tremor in a multiple sclerosis model

Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis1 . Although both these diseases are typi®ed by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens1 Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are dif®cult to control. This has prompted some patients to ®nd alternative medicines, and to perceive bene®t from cannabis use2 . Although this bene®t has been backed up by small clinical studies, mainly with non-quanti®able outcomes3±7, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, D9 – tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients’ indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis2 , and provides a means of evaluating more selective cannabinoids in the future