ENCEPHALOMYELITIS/ EAE & Cannabis Studies Completed
Overview
Encephalomyelitis is a general term for inflammation of the brain and spinal cord, describing a number of disorders:
- Acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by viral infection;
- Encephalomyelitis disseminata, a synonym for multiple sclerosis;
- Equine encephalomyelitis, a potentially fatal mosquito-borne viral disease that infects horses and humans;
- Myalgic encephalomyelitis, a syndrome involving inflammation of the central nervous system with symptoms of muscle pain and fatigue; the term has sometimes been used interchangeably with chronic fatigue syndrome, though there is still controversy over the distinction.
- Experimental autoimmune encephalomyelitis (EAE), an animal model of brain inflammation.
Science and Research
2012 - Study ~ Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB(1) receptor-mediated anti-inflammatory effects.
2012 - Study ~ Cannabinoid receptor 2 agonists inhibit migration of activated dendritic cells via modulation of MMP-9
2011 - Study ~ Administration of 2-arachidonoylglycerol ameliorates both acute and chronic Experimental Autoimmune Encephalomyelitis
2009 - Study ~ Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke
2008 - Study ~ The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis.
2008 - Study ~ CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies
2008 - Study ~ Cannabinoids in the management of spasticity associated with multiple sclerosis
2007 - Study - The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis
2007 - Study ~ Control of Spasticity in a Multiple Sclerosis Model is mediated by CB1, not CB2, Cannabinoid Receptors2007 - Study ~ A Cannabinoid CB2 receptor agonist attenuates experimental autoimmune encephalomyelitis (EAE) and reduces MOG-specific T cell proliferation
2006 - Study ~ Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection
2005 - Study ~ Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and caspase 3 activation.
2003 - Study ~ Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R(+) WIN55,212
1997 - Study ~ Suppression of experimental autoimmune encephalomyelitis by cannabinoids.
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The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis
- Oxford Journals
- Medicine
- Brain
- Volume130, Issue10
- Pp. 2543-2553
Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy, Centro Europeo per la Ricerca sul Cervello (CERC)/Fondazione Santa Lucia, Rome, Italy, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università Tor Vergata, Rome, Italy, Neuroimmunology Unit, DIBIT, San Raffaele Scientific Institute, Milan, Italy, Dipartimento di Medicina Interna, Medicina di Laboratorio, Università Tor Vergata, Rome, Italy and Dipartimento di Scienze Biomediche, Università degli Studi di Teramo, Teramo, Italy
- Correspondence to: Diego Centonze, Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy E-mail: centonze@uniroma2.it
- Mauro Maccarrone, Dipartimento di Scienze Biomediche, Università degli Studi di Teramo, Piazza A. Moro 45, 64100 Teramo, Italy E-mail: mmaccarrone@unite.it
- Received December 22, 2006.
- Revision received May 10, 2007.
- Accepted June 14, 2007.
Summary
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 show that MS and EAE are associated with significant alterations of the endocannabinoid system. We found that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was increased in the CSF of relapsing MS patients. AEA concentrations were also higher in peripheral lymphocytes of these patients, an effect associated with increased synthesis and reduced degradation of this endocannabinoid. Increased synthesis, reduced degradation, and increased levels of AEA were also detected in the brains of EAE mice in the acute phase of the disease, possibly accounting for its anti-excitotoxic action in this disorder. Accordingly, neurophysiological recordings from single neurons confirmed that excitatory transmission in EAE slices is inhibited by CB1 receptor activation, while inhibitory transmission is not. Our study suggests that targeting the endocannabinoid system might be useful for the treatment of MS.
- Abbreviations:
- AEA
- anandamide
- 2-AG
- 2-arachidonoylglycerol
- CB
- cannabinoid
- CSF
- cerebrospinal fluid
- EAE
- experimental autoimmune encephalomyelitis
- ECS
- endocannabinoid system
- EPSC
- excitatory postsynaptic current
- FAAH
- fatty acid amide hydrolase
- HP
- holding potential
- IPSC
- inhibitory postsynaptic current
- MS
- multiple sclerosis
- NAPE-PLD
- N-acyl-phosphatidylethanolamines (NAPE)-hydrolysing phospholipase D
- PPR
- paired pulse ratio
- © The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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- Translational Research in Neurology and Neuroscience 2010: Multiple Sclerosis Arch Neurol (2010) 67(11): 1307-1315
- Alterations of the endocannabinoid system in an animal model of migraine: Evaluation in cerebral areas of rat Cephalalgia (2010) 30(3): 296-302
- The cannabinoid receptor 1 gene (CNR1) and multiple sclerosis: an association study in two case-control groups from Spain Mult Scler (2010) 16(2): 139-146
- Cannabinoid Receptor Type 1- and 2-mediated Increase in Cyclic AMP Inhibits T Cell Receptor-triggered Signaling J. Biol. Chem. (2009) 284(51): 35450-35460
- Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity Brain (2009) 132(11): 3152-3164
- ALTERED ANANDAMIDE DEGRADATION IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER Neurology (2009) 72(17): 1526-1527
- Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis J. Neurosci. (2009) 29(11): 3442-3452
- Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis J. Neurol. Neurosurg. Psychiatry (2008) 79(11): 1224-1229
- Anandamide as a Marker of Human Disease JAMA (2008) 300(3): 281-282
CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies
Br J Pharmacol. 2008 January; 153(2): 216–225. | PMCID: PMC2219542 |

Figure 1 Hypothetic immune-mediated demyelinating disease pathogenesis. Primed CD4+ T lymphocytes migrate to the CNS through blood vessels enriched in adhesion molecules. Once in the CNS, DCs or macrophages/microglia acting as APC present the antigen to (more ...) |
Since the late 1970s, it was clear that the psychoactive compounds of Cannabis sativa, such as delta-9-tetrahydrocannabinol (Δ9-THC), modulate the inflammatory response (Zimmerman et al., 1977; Smith et al., 1978). In the following years, numerous studies...read entire study