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Cannabinoids control spasticity and tremor in a multiple sclerosis model

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Abstract

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.

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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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Neurochemistry, Neuroinflammation Group, Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ

    David Baker, Gareth Pryce & J. Ludovic Croxford

  2. Institute of Ophthalmology, UCL, London, EC1V 9EL, UK

    David Baker, Gareth Pryce & J. Ludovic Croxford

  3. The Medical Research Council Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery , Queen Square, London, WC1N 3BG, UK

    Peter Brown

  4. Department of Biomedical Sciences Institute of Medical Sciences, University of Aberdeen, Foresterhill , Aberdeen, AB25 2ZD, UK

    Roger G. Pertwee

  5. Department of Chemistry, Clemson University, Clemson, 29634-1905 , South Carolina, USA

    John W. Huffman

  6. Multiple Sclerosis Society of Great Britain and Northern Ireland , 25 Effie Road, London, SW6 1EE, UK

    Lorna Layward

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  1. David Baker
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  2. Gareth Pryce
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  5. Roger G. Pertwee
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  7. Lorna Layward
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Correspondence to David Baker.

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Baker, D., Pryce, G., Croxford, J. et al. Cannabinoids control spasticity and tremor in a multiple sclerosis model . Nature 404, 84–87 (2000). https://doi.org/10.1038/35003583

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  • DOI: https://doi.org/10.1038/35003583

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