title: Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice.
abstract: Cannabinoids (CBs) have recently been approved to exert broad anti-inflammatory activities in experimental models of multiple sclerosis (MS). It has been demonstrated that these compounds could also have effects on neurodegeneration, demyelination, and autoimmune processes occurring in the pathology of MS. However, the clinical use of CBs is limited by their psychoactive effects. Among cannabinoid compounds, cannabidiol (CBD) and palmitoylethanolamide (PEA) have no psychotropic activities. We induced experimental autoimmune encephalomyelitis (EAE), a model of MS, by injecting myelin oligodendrocyte glycoprotein (MOG) to C57BL/6 mice. We assessed the effects of CBD, PEA, and co-administration of CBD and PEA on neurobehavioral scores, immune cell infiltration, demyelination, axonal injury, and the expression of inflammatory cytokines by using histochemistry methods and real-time RT-PCR. Treatment with either CBD (5mg/kg) or PEA (5mg/kg) during disease onset reduced the severity of the neurobehavioral scores of EAE. This effect of CBD and PEA was accompanied by diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression while concurrent administration of CBD (5mg/kg) and PEA (5mg/kg) was not as effective as treatment with either drug per se. These results suggest that, CBD and PEA, non-psychoactive CBs, attenuate neurobehavioral deficits, histological damage, and inflammatory cytokine expression in MOG-immunized animals. However, there is an antagonistic interaction between CBD and PEA in protection against MOG-induced disease.
authors: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: A
authors: A
authors: Rahimi
authors: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: M
authors: M
authors: Faizi
authors: Khatam-Al-Anbia Hospital, Shefa Neuroscience Research Center, Tehran, Iran.
authors: F
authors: F
authors: Talebi
authors: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: F
authors: F
authors: Noorbakhsh
authors: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: F
authors: F
authors: Kahrizi
authors: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: N
authors: N
authors: Naderi
mesh_terms: D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002185:Cannabidiol / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects; D010169:Palmitic Acids / Q000494:pharmacology*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D004983:Ethanolamines; D020381:Interleukin-17; D010169:Palmitic Acids; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; C005958:palmidrol; D007371:Interferon-gamma
keywords: EAE; cannabidiol; cannabinoid; multiple sclerosis; palmitoylethanolamide