大麻二酚(CBD)是源自大麻的一组植物大麻素的一部分。对CBD的初步工作假定该化合物不活跃,但后来发现它表现出抗精神病药,抗抑郁药,抗焦虑药,和抗癫痫作用。近几十年来,证据表明CBD在调节线粒体过程中的作用,包括呼吸和生物能学,线粒体DNA表观遗传学,内在凋亡,线粒体和细胞内钙浓度的调节,线粒体裂变,融合和生物发生,线粒体铁蛋白浓度和线粒体单胺氧化酶活性调控。尽管取得了这些进展,目前的数据表明,不仅在CBD介导的影响程度方面存在矛盾的发现,也是影响的方向。例如,有数据表明CBD治疗可以增加,减少,或对内在细胞凋亡没有显著影响。细胞类型研究之间的差异,对CBD的细胞特异性反应,and,在某些情况下,CBD的剂量可能有助于解释结果的差异.大多数关于CBD和线粒体的研究都利用了超过人类最高记录血浆浓度的治疗浓度,建议未来的研究应集中在药代动力学研究中观察到的范围内的CBD治疗。这篇综述着重于理解CBD介导的线粒体功能调节的机制。强调神经细胞和组织的发现以及基于人体药代动力学的治疗相关性。
Cannabidiol (CBD) is part of a group of phytocannabinoids derived from Cannabissativa. Initial work on CBD presumed the compound was inactive, but it was later found to exhibit antipsychotic, anti-depressive, anxiolytic, and antiepileptic effects. In recent decades, evidence has indicated a role for CBD in the modulation of mitochondrial processes, including respiration and bioenergetics, mitochondrial DNA epigenetics, intrinsic apoptosis, the regulation of mitochondrial and intracellular calcium concentrations, mitochondrial fission, fusion and biogenesis, and mitochondrial ferritin concentration and mitochondrial monoamine oxidase activity regulation. Despite these advances, current data demonstrate contradictory findings with regard to not only the magnitude of effects mediated by CBD, but also to the direction of effects. For example, there are data indicating that CBD treatment can increase, decrease, or have no significant effect on intrinsic apoptosis. Differences between studies in cell type, cell-specific response to CBD, and, in some cases, dose of CBD may help to explain differences in outcomes. Most studies on CBD and mitochondria have utilized treatment concentrations that exceed the highest recorded plasma concentrations in humans, suggesting that future studies should focus on CBD treatments within a range observed in pharmacokinetic studies. This
review focuses on understanding the mechanisms of CBD-mediated regulation of mitochondrial functions, with an emphasis on findings in neural cells and tissues and therapeutic relevance based on human pharmacokinetics.