Abstract
Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aspartic Acid / analogs & derivatives*
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Aspartic Acid / analysis
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Axons / chemistry
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Axons / pathology
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Benzoxazines
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Cannabinoids / therapeutic use*
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Cyclohexanols / therapeutic use
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Dizocilpine Maleate / therapeutic use
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Encephalomyelitis, Autoimmune, Experimental
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Excitatory Amino Acid Agonists / therapeutic use
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Gene Deletion
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Humans
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Mice
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Mice, Transgenic
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Monomeric GTP-Binding Proteins / genetics
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Morpholines / therapeutic use
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / pathology
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N-Methylaspartate / therapeutic use
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Naphthalenes / therapeutic use
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Nerve Degeneration
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Nuclear Proteins / genetics
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Receptors, Cannabinoid
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Receptors, Drug / agonists
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Retina / drug effects
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Retina / pathology
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Saccharomyces cerevisiae Proteins*
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Spinal Cord / pathology
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Uveitis / immunology
Substances
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Benzoxazines
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Cannabinoids
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Cyclohexanols
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Excitatory Amino Acid Agonists
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GSP1 protein, S cerevisiae
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Morpholines
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Naphthalenes
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Nuclear Proteins
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Receptors, Cannabinoid
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Receptors, Drug
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Receptors, N-Methyl-D-Aspartate
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Saccharomyces cerevisiae Proteins
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Aspartic Acid
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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N-Methylaspartate
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Dizocilpine Maleate
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3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
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N-acetylaspartate
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Monomeric GTP-Binding Proteins