Endocannabinoids control spasticity in a multiple sclerosis model.

D. Baker, G. Pryce, J. L. Croxford, P. Brown, Roger Guy Pertwee, A. Makriyannis, A. Khanolkar, F. Fezza, T. Bisogno, V. Di Marzo

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348 Citations (Scopus)

Abstract

Spasticity is a complicating sign in multiple sclerosis that also develops in a model of chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice. In areas associated with nerve damage, increased levels of the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoyl glycerol (2-AG), and of the AEA congener, palmitoylethanolamide (PEA), were detected here, whereas comparable levels of these compounds were found in normal and non-spastic CREAE mice. While exogenously administered endocannabinoids and PEA ameliorate spasticity, selective inhibitors of endocannabinoid re-uptake and hydrolysis-probably through the enhancement of endogenous levels of AEA, and, possibly, 2-arachidonoyl glycerol-significantly ameliorated spasticity to an extent comparable with that observed previously with potent cannabinoid receptor agonists. These studies provide definitive evidence for the tonic control of spasticity by the endocannabinoid system and open new horizons to therapy of multiple sclerosis, and other neuromuscular diseases, based on agents modulating endocannabinoid levels and action, which exhibit little psychotropic activity.

Original languageEnglish
Pages (from-to)300-302
Number of pages2
JournalThe FASEB Journal
Volume15
Issue number2
Early online date8 Dec 2000
DOIs
Publication statusPublished - Feb 2001

Keywords

  • autoimmune encephalomyelitis
  • multiple sclerosis
  • anandamide
  • 2-arachidonoyl-glycerol
  • palmitoylethanolamide
  • cannabioid

Cite this

Baker, D., Pryce, G., Croxford, J. L., Brown, P., Pertwee, R. G., Makriyannis, A., Khanolkar, A., Fezza, F., Bisogno, T., & Di Marzo, V. (2001). Endocannabinoids control spasticity in a multiple sclerosis model. The FASEB Journal, 15(2), 300-302. https://doi.org/10.1096/fj.00-0399fje