Abstract:
Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler\'s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.
摘要:
尽管目前的免疫调节和缓解多发性硬化症(MS)症状的治疗策略,由于动态神经病变和复发,髓鞘再生不足,导致残疾和相关患者不满的累积。大麻素的潜力包括附加免疫抑制,镇痛药,神经保护,和髓鞘再生作用。本研究评估了医用大麻在MS及其实验动物模型中的功效。通过PubMed的文献检索进行了系统的综述,ProQuest,和EBSCO电子数据库的研究报告自2007年以来使用大麻二酚(CBD)和δ-9-四氢大麻酚(THC)在MS和实验性自身免疫性脑脊髓炎(EAE),泰勒鼠脑脊髓炎病毒诱导的脱髓鞘病(TMEV-IDD),和毒素诱导的脱髓鞘模型。研究选择和数据提取由3名评审员进行,28项研究入选.使用Cochrane等级方法评估证据的确定性。在临床研究中,有低质量和中等质量的证据表明,使用〜1:1CBD/THC混合物作为纳比肟(Sativex®)口腔粘膜喷雾剂可降低痉挛状态的数字评分(NRS)评分,疼痛,和睡眠障碍,膀胱过度活动减少,并降低促炎细胞因子和转录因子的表达水平。临床前研究表明疾病严重程度降低,后肢僵硬度,运动功能,神经炎症,和脱髓鞘.其他实验系统通过电子显微镜显示了大麻素促进体外髓鞘再生的能力。在使用CBD/THC混合物的辅助治疗的MS应答者中实现了适度的短期益处。建议进行未来的研究,以研究大麻素对MS病变的影响的细胞和分子机制,并评估医用大麻是否可以长期加速髓鞘再生和延缓残疾的增加。