Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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 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 outcomes3,4,5,6,7, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, Δ9-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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cannabinoid receptor agonism inhibits tremor in autoimmune encephalomyelitis1.
Figure 2: Spasticity develops in autoimmune encephalomyelitis1.
Figure 3: Control of spasticity by the cannabinoid system.
Figure 4: Treatment of spasticity in autoimmune encephalomyelitis1 with non-CB1 receptor agonists.

Similar content being viewed by others


  1. Baker, D. et al. Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice. J. Neuroimmunol. 28, 261 –270 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Consroe, P., Musty, R., Rein, J., Tillery, W. & Pertwee, R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur. Neurol. 38, 44–48 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. Consroe, P. Cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol. Dis. 5, 534– 551 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Petro, D. J. & Ellenberger, C. Treatment of human spasticity with Δ9-tetrahydrocannabinol. J. Clin. Pharmacol. 21 (suppl.), 413–416 ( 1981).

    Article  Google Scholar 

  5. Clifford, D. B. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann. Neurol. 13, 669–671 ( 1983).

    Article  CAS  PubMed  Google Scholar 

  6. Ungerleider, J. T., Andyrsiak, T., Fairbanks, L., Ellison, G. W. & Myers, L. W. Δ9-THC in the treatment of spasticity associated with multiple sclerosis. Adv. Alcohol Substance Abuse 7, 39– 50 (1987).

    Article  CAS  Google Scholar 

  7. Martyn, C. N., Illis, L. S. & Thom, J. Nabilone in the treatment of multiple sclerosis. Lancet 345, 579 (1995).

    Article  CAS  PubMed  Google Scholar 

  8. Pertwee, R. G. Pharmacology of cannabinoid receptor ligands. Curr. Med. Chem. 6, 635–664 ( 1999).

    CAS  PubMed  Google Scholar 

  9. Lyman, W. D., Sonett, J. R., Brosnan, C. F., Elkin, R. & Bornstein, M. B. Δ9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J. Neuroimmunol. 23, 73–81 (1989).

    Article  CAS  PubMed  Google Scholar 

  10. Wirguin, I. et al. Suppression of experimental autoimmune encephalomyelitis by cannabinoids. Immunopharmacology 28, 209 –214 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Heller, A. H. & Hallet, M. Electrophysiological studies with the spastic mutant mouse. Brain Res. 234, 299–308 (1982).

    Article  CAS  PubMed  Google Scholar 

  12. Chai, C. K. Hereditary spasticity in mice. J. Heredity 52, 241–243 (1961).

    Article  Google Scholar 

  13. Pertwee, R. G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Therapeut. 74, 129–180 ( 1997).

    CAS  Google Scholar 

  14. Breivogel, C. S. & Childers, S. R. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol. Dis. 5, 417–431 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Landsman, R. S., Burkey, T. H., Consroe, P., Roeske, W. R. & Yamamura, H. I. SR141716A is an inverse agonist at the human cannabinoid CB1 receptor. Eur. J. Pharmacol. 334, R1–R2 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Portier, M. et al. SR144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist. J. Pharmacol Exp. Ther. 288, 582–589 (1999).

    CAS  PubMed  Google Scholar 

  17. Calignano, A., La Rana, G., Giuffrida, A. & Piomelli, D. Control of pain initiation by endogenous cannabinoids. Nature 394, 277–281 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Giuffrida, A. et al. Dopamine activation of endogenous cannabinoid signalling in dorsal striatum. Nature Neurosci. 2, 358 –363 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Huffman, J. W. et al. 3-(1′,1′-Dimethylbutyl)-1-deoxy-Δ9-THC and related compounds: synthesis of selective ligands for the CB2 receptor. Bioorg. Med. Chem. 7, 2905–2914 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Noth, J. Trends in the pathophysiology and pharmacotherapy of spasticity. J. Neurol. 238, 131–139 (1991).

    Article  CAS  PubMed  Google Scholar 

Download references


The authors would like to thank the Multiple Sclerosis Society of Great Britain and Northern Ireland, the Medical Research Council, the National Institute on Drug Abuse and the Wellcome Trust for their financial support.

Author information

Authors and Affiliations


Corresponding author

Correspondence to David Baker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baker, D., Pryce, G., Croxford, J. et al. Cannabinoids control spasticity and tremor in a multiple sclerosis model . Nature 404, 84–87 (2000).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing