Cannabinoids control spasticity and tremor in a multiple sclerosis model

Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an aut oimmune model of multiple sclerosis(1). Although both these diseases are ty pified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens(1) Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are di fficult to control. This has prompted some patients to find alternative med icines, and to perceive benefit from cannabis use(2), Although this benefit has been backed up by small clinical studies, mainly With non-quantifiable outcomes(3-7) the value of cannabis use in multiple sclerosis remains anec dotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 5 5,212, Delta(9)-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) q uantitatively 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) indicative that the endogenous cannabinoid system may be tonically active in the contr ol of tremor and spasticity. This provides a rationale for patients' indica tions of the therapeutic potential of cannabis in the control of the sympto ms of multiple sclerosis(2), and provides a means of evaluating more select ive cannabinoids in the future.