The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis.

  title={The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis.},
  author={Diego Centonze and Monica Bari and Silvia Rossi and Chiara Prosperetti and Roberto Furlan and Filomena Fezza and Valentina De Chiara and Luca Battistini and Giorgio Bernardi and Sergio Bernardini and Gianvito Martino and Mauro Maccarrone},
  journal={Brain : a journal of neurology},
  volume={130 Pt 10},
The ability of cannabinoids to modulate both inflammatory and degenerative neuronal damage prompted investigations on the potential benefits of such compounds in multiple sclerosis (MS) and in animal models of this disorder. Here we measured endocannabinoid levels, metabolism and binding, and physiological activities in 26 patients with MS (17 females, aged 19-43 years), 25 healthy controls and in mice with experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. Our results… 

Figures from this paper

Cannabinoids, multiple sclerosis and neuroprotection

The present review will be precisely centered on this neuroprotective potential, which is based mainly on antioxidant, anti-inflammatory and anti-excitotoxic properties, exerted through the activation of CB1 or CB2 receptors or other unknown mechanisms.

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis : Clues for other neuroin fl ammatory diseases

The preclinical and clinical studies that could explain the therapeutic action of cannabinoid-based medicines, as well as the medical potential of modulating endocannabinoid signaling in multiple sclerosis, with a link to other neuroinflammatory disorders that share common hallmarks and pathogenetic features are reviewed.

Selective Endocannabinoid Reuptake Inhibitor WOBE437 Reduces Disease Progression in a Mouse Model of Multiple Sclerosis

The results show that WOBE437 (and SERIs) may represent a novel therapeutic strategy for slowing MS progression and control major symptoms.

Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction.

Sativex® (nabiximols, USAN name) contains the two main phytocannabinoids from Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 ratio, and it acts as an endocannabinoid system modulator.

Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis

The present findings suggest the presence of an impaired eCB system in MS and provide further support for the development of drugs targeting eCBs as a potential pharmacological strategy to reduce the symptoms and slow disease progression in MS.

Therapeutic implications of the endocannabinoid system in neurodegenerative diseases

The purpose of this review is to present the available research and clinical data, up to date, regarding therapeutic perspectives of the endocannabinoid system in such neurodegenerative diseases.



Activation of the endocannabinoid system as a therapeutic approach in a murine model of multiple sclerosis

The results indicate that treatment during established disease significantly improves the motor function of the diseased mice and suggest that agents able to activate the endocannabinoid system could constitute a new series of drugs for the treatment of MS.

Multiple sclerosis may disrupt endocannabinoid brain protection mechanism.

  • E. ShohamiR. Mechoulam
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2006
It is demonstrated that, unexpectedly and contrary to the effects of other brain diseases, cell damage induced by experimental autoimmune encephalomyelitis (EAE), an immune-mediated disease widely used as a laboratory model of multiple sclerosis (MS), does not lead to enhancement of eCB levels, although the cannabinoid receptors remain functional.

Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis

OMDM1 and OMDM2 provide an effective therapy for Theiler murine encephalomyelitis virus‐induced demyelinating disease (TMEV‐IDD) and point to the manipulation of the endocannabinoid system as a possible strategy to develop future MS therapeutic drugs.

Therapeutic Action of Cannabinoids in a Murine Model of Multiple Sclerosis

Treatment with the synthetic cannabinoids WIN 55,212–2, ACEA, and JWH-015 during established disease significantly improved the neurological deficits in a long-lasting way and the possible involvement of cannabinoid receptor CB2 would enable nonpsychoactive therapy suitable for long-term use.

Δ 9-Tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis

Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis.

As delta 9-Tetrahydrocannabinol has been shown to inhibit both clinical and histologic EAE, it may prove to be a new and relatively innocuous agent for the treatment of immune-mediated diseases.

Endocannabinoids control spasticity in a multiple sclerosis model

  • D. BakerG. Pryce V. Marzo
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2001
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 endoc cannabinoidoid levels and action, which exhibit little psychotropic activity.

The endocannabinoid system in targeting inflammatory neurodegenerative diseases.

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection.

It is shown that cell damage induced by EAE does not lead to increase in eCBs, even though cannabinoid receptors are functional because synthetic cannabinoid agonists are known to confine EAE-induced lesions, and IFN-gamma, which is released by primed T cells invading the CNS, disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors.

Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R(+)WIN55,212

It is shown that the cannabinoid receptor agonist, R(+)WIN55,212, ameliorates progression of clinical disease symptoms in mice with preexisting TMEV-IDD, and may also have potent immunoregulatory properties.