From cannabis to endocannabinoids in multiple sclerosis: a paradigm of central nervous system autoimmune diseases.

Anna Maria Malfitano, Giuseppe Matarese, Maurizio Bifulco
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引用次数: 18

Abstract

An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of multiple sclerosis, including spasticity and pain. Endogenous molecules with cannabinoid-like activity, such as the "endocannabinoids", have been shown to mimic the anti-inflammatory properties of cannabinoids through the cannabinoid receptors. Several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis. Indeed, they can down regulate the production of pathogenic T helper 1-associated cytokines enhancing the production of T helper 2-associated protective cytokines. A shift towards T helper 2 has been associated with therapeutic benefit in multiple sclerosis. In addition, cannabinoids exert a neuromodulatory effect on neurotransmitters and hormones involved in the neurodegenerative phase of the disease. In vivo studies using mice with experimental allergic encephalomyelitis, an animal model of multiple sclerosis, suggest that the increase of the circulating levels of endocannabinoids might have a therapeutic effect, and that agonists of endocannabinoids with low psychoactive effects could open new strategies for the treatment of multiple sclerosis.

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从大麻到内源性大麻素在多发性硬化症:中枢神经系统自身免疫性疾病的范例。
越来越多的证据表明,大麻素对多发性硬化症的症状有有益的作用,包括痉挛和疼痛。具有类似大麻素活性的内源性分子,如“内源性大麻素”,已被证明通过大麻素受体模仿大麻素的抗炎特性。一些研究表明大麻素和内源性大麻素可能在多发性硬化症的发病和治疗中起关键作用。事实上,它们可以下调致病性辅助性T - 1相关细胞因子的产生,增强辅助性T - 2相关保护性细胞因子的产生。向辅助T - 2的转变与多发性硬化症的治疗益处有关。此外,大麻素对参与疾病神经退行性阶段的神经递质和激素发挥神经调节作用。对多发性硬化症动物模型——实验性过敏性脑脊髓炎小鼠的体内研究表明,增加内源性大麻素的循环水平可能具有治疗作用,而内源性大麻素激动剂具有低精神活性作用,可能为多发性硬化症的治疗开辟新的策略。
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Cannabinoids. The endocannabinoid system in the brain: from biology to therapy. Endocannabinoid metabolic pathways and enzymes. Molecular biology of the enzymes that degrade endocannabinoids. Endocannabinoids in the central nervous system: from neuronal networks to behavior.
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