Russo Ethan B
International Cannabis and Cannabinoids Institute (ICCI), Prague, Czechia.
Front Integr Neurosci. 2018 Oct 18;12:51. doi: 10.3389/fnint.2018.00051. eCollection 2018.
Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB and CB (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.
神经治疗一直受到阻碍,因为它无法超越神经退行性疾病的症状治疗,进入实际缓解、阻止或逆转相关病理过程的领域。虽然基于大麻的药物已证明其安全性、有效性和一致性足以获得监管部门对多发性硬化症(MS)痉挛、德雷维特综合征和伦诺克斯 - 加斯托综合征(LGS)的批准,但仍存在许多治疗挑战。本综述将探讨基于大麻的药物的最新发现为神经治疗带来的诱人前景,这些发现涉及中性植物大麻素四氢大麻酚(THC)、大麻二酚(CBD)、它们的酸性前体四氢大麻酚酸(THCA)和大麻二酚酸(CBDA),以及大麻萜类化合物在五种目前被认为治疗效果不佳且需要改进药物干预的综合征中的假定治疗作用:难治性癫痫、脑肿瘤、帕金森病(PD)、阿尔茨海默病(AD)和创伤性脑损伤(TBI)/慢性创伤性脑病(CTE)。目前的基础科学和临床研究支持此类干预措施在治疗这些目前难以治疗的疾病方面的安全性和有效性,这些疾病在某些情况下具有共同的病理过程,以及利用内源性大麻素机制进行干预的合理性,无论这种干预是通过对CB1和CB2(四氢大麻酚、THC、石竹烯)的直接作用、过氧化物酶体增殖物激活受体 - γ(PPARγ;THCA)、5 - 羟色胺(CBD、CBDA)介导,还是甚至通过使用益生元和益生菌的营养方法介导。大麻植物固有的多药特性相对于当前的单靶点药物模型具有明显优势,并预示着神经治疗将彻底变革为有效干预甚至预防性治疗的新现实。