1. Neuroinflammation Group, Department of Neurochemistry, Institute of Neurology, University College London, 1 Wakefield Street, London WC1N 1PJ and the Institute of Ophthalmology, UCL, London EC1V 9EL, UK
2. The Medical Research Council Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery , Queen Square, London, WC1N 3BG, UK
3. Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill , Aberdeen AB25 2ZD, UK
4. Department of Chemistry, Clemson University, Clemson, South Carolina 29634-1905 , USA
5. Multiple Sclerosis Society of Great Britain and Northern Ireland , 25 Effie Road, London SW6 1EE, UK

Correspondence to: Correspondence and requests for materials should be addressed to D.B. (e-mail: Email: D.Baker@ion.ucl.ac.uk).

Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis¹. Although both these diseases are typified 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 difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use². Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes^{3, 4, 5, 6, 7}, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, ⁹-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.