CIS Clinical Investigation Support GmbH, Kaiserstrasse 43, 1070, Wien, Austria.
Pharmaceut Med. 2022 Apr;36(2):99-129. doi: 10.1007/s40290-022-00420-4. Epub 2022 Mar 4.
Preclinical models provided ample evidence that cannabinoids are cytotoxic against cancer cells. Among the best studied phytocannabinoids, cannabidiol (CBD) is most promising for the treatment of cancer as it lacks the psychotomimetic properties of delta-9-tetrahydrocannabinol (THC). In vitro studies and animal experiments point to a concentration- (dose-)dependent anticancer effect. The effectiveness of pure compounds versus extracts is the subject of an ongoing debate. Actual results demonstrate that CBD-rich hemp extracts must be distinguished from THC-rich cannabis preparations. Whereas pure CBD was superior to CBD-rich extracts in most in vitro experiments, the opposite was observed for pure THC and THC-rich extracts, although exceptions were noted. The cytotoxic effects of CBD, THC and extracts seem to depend not only on the nature of cannabinoids and the presence of other phytochemicals but also largely on the nature of cell lines and test conditions. Neither CBD nor THC are universally efficacious in reducing cancer cell viability. The combination of pure cannabinoids may have advantages over single agents, although the optimal ratio seems to depend on the nature of cancer cells; the existence of a 'one size fits all' ratio is very unlikely. As cannabinoids interfere with the endocannabinoid system (ECS), a better understanding of the circadian rhythmicity of the ECS, particularly endocannabinoids and receptors, as well as of the rhythmicity of biological processes related to the growth of cancer cells, could enhance the efficacy of a therapy with cannabinoids by optimization of the timing of the administration, as has already been reported for some of the canonical chemotherapeutics. Theoretically, a CBD dose administered at noon could increase the peak of anandamide and therefore the effects triggered by this agent. Despite the abundance of preclinical articles published over the last 2 decades, well-designed controlled clinical trials on CBD in cancer are still missing. The number of observations in cancer patients, paired with the anticancer activity repeatedly reported in preclinical in vitro and in vivo studies warrants serious scientific exploration moving forward.
临床前模型提供了充分的证据表明大麻素对癌细胞具有细胞毒性。在研究最多的植物大麻素中，大麻二酚（CBD）最有希望用于治疗癌症，因为它缺乏Δ-9-四氢大麻酚（THC）的致幻特性。体外研究和动物实验表明存在浓度（剂量）依赖性的抗癌作用。关于纯化合物与提取物的有效性是一个正在争论的问题。实际结果表明，必须将富含 CBD 的大麻提取物与富含 THC 的大麻制剂区分开来。虽然在大多数体外实验中，纯 CBD 优于富含 CBD 的提取物，但在纯 THC 和富含 THC 的提取物中则相反，尽管也有例外。CBD、THC 和提取物的细胞毒性作用似乎不仅取决于大麻素的性质和其他植物化学物质的存在，而且还在很大程度上取决于细胞系和测试条件的性质。CBD 和 THC 都不能普遍有效地降低癌细胞活力。纯大麻素的组合可能比单一药物具有优势，尽管最佳比例似乎取决于癌细胞的性质；不太可能存在“一刀切”的比例。由于大麻素会干扰内源性大麻素系统（ECS），因此更好地了解 ECS 的昼夜节律性，特别是内源性大麻素和受体，以及与癌细胞生长相关的生物过程的节律性，通过优化给药时间来增强大麻素治疗的效果，正如已经报道的一些经典化学疗法一样。从理论上讲，中午给予 CBD 剂量可以增加花生四烯酸酰胺的峰值，从而增加该药物引发的作用。尽管在过去 20 年中发表了大量的临床前文章，但仍缺乏关于 CBD 在癌症中的对照临床试验。癌症患者的观察数量与在临床前体外和体内研究中反复报道的抗癌活性相结合， warrants serious scientific exploration moving forward.
