Rahimi A, Faizi M, Talebi F, Noorbakhsh F, Kahrizi F, Naderi N
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Khatam-Al-Anbia Hospital, Shefa Neuroscience Research Center, Tehran, Iran.
Neuroscience. 2015 Apr 2;290:279-87. doi: 10.1016/j.neuroscience.2015.01.030. Epub 2015 Jan 28.
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.
大麻素（CBs）最近已被批准在多发性硬化症（MS）的实验模型中发挥广泛的抗炎活性。已经证明，这些化合物对MS病理过程中发生的神经变性、脱髓鞘和自身免疫过程也可能有影响。然而，CBs的临床应用受到其精神活性作用的限制。在大麻素化合物中，大麻二酚（CBD）和棕榈酰乙醇胺（PEA）没有精神活性。我们通过向C57BL/6小鼠注射髓鞘少突胶质细胞糖蛋白（MOG）诱导实验性自身免疫性脑脊髓炎（EAE），这是一种MS模型。我们使用组织化学方法和实时RT-PCR评估了CBD、PEA以及CBD与PEA联合给药对神经行为评分、免疫细胞浸润、脱髓鞘、轴突损伤和炎性细胞因子表达的影响。在疾病发作期间用CBD（5mg/kg）或PEA（5mg/kg）治疗可降低EAE的神经行为评分严重程度。CBD和PEA的这种作用伴随着炎症、脱髓鞘、轴突损伤和炎性细胞因子表达的减轻，而同时给予CBD（5mg/kg）和PEA（5mg/kg）的效果不如单独使用任何一种药物。这些结果表明，非精神活性的CBs，即CBD和PEA，可减轻MOG免疫动物的神经行为缺陷、组织学损伤和炎性细胞因子表达。然而，在预防MOG诱导的疾病方面，CBD和PEA之间存在拮抗相互作用。
