Maguire Ryan F, Wilkinson Daniel J, England Timothy J, O'Sullivan Saoirse E
Division of Graduate Entry Medicine and Medical Sciences, School of Medicine, University of Nottingham, Royal Derby Hospital, Nottingham, United Kingdom.
Department of Stroke, University Hospitals of Derby and Burton, Derby, United Kingdom.
Med Cannabis Cannabinoids. 2021 Jul 29;4(2):86-96. doi: 10.1159/000517120. eCollection 2021 Winter.
Cannabidiol (CBD) can be isolated from L. or synthetically produced. The aim of this study was to compare the in vitro effects of purified natural and synthetic CBD to establish any pharmacological differences or superiority between sources.
Six purified samples of CBD were obtained, 4 of these were natural and 2 synthetic. The anticancer effects of CBD were assessed in a human ovarian cancer cell line (SKOV-3 cells). The neuroprotective effects of CBD were assessed in human pericytes in a model of stroke (oxygen glucose deprivation [OGD]). The ability of CBD to restore inflammation-induced intestinal permeability was assessed in differentiated human Caco-2 cells (a model of enterocytes).
(1) In proliferating and confluent SKOV-3 cells, all CBD samples similarly reduced resazurin metabolism as a marker of cell viability in a concentration-dependent manner ( < 0.001). (2) In pericytes exposed to OGD, all CBD samples similarly reduced cellular damage (measured by lactate dehydrogenase) at 24 h by 31-48% and reduced inflammation (measured by IL-6 secretion) by 30-53%. Attenuation of IL-6 was inhibited by 5HT receptor antagonism for all CBD sources. (3) In differentiated Caco-2 cells exposed to inflammation (TNFα and IFNγ, 10 ng/mL for 24 h), each CBD sample increased the speed of recovery of epithelial permeability compared to control ( < 0.05-0.001), which was inhibited by a CB receptor antagonist.
Our results suggest that there is no pharmacological difference in vitro in the antiproliferative, anti-inflammatory, or permeability effects of purified natural versus synthetic CBD. The purity and reliability of CBD samples, as well as the ultimate pharmaceutical preparation, should all be considered above the starting source of CBD in the development of new CBD medicines.
大麻二酚(CBD)可从大麻中分离得到或通过合成生产。本研究的目的是比较纯化的天然和合成CBD的体外效应,以确定不同来源之间是否存在任何药理学差异或优势。
获得了6个CBD纯化样品,其中4个是天然的,2个是合成的。在人卵巢癌细胞系(SKOV-3细胞)中评估了CBD的抗癌作用。在中风模型(氧糖剥夺[OGD])中的人周细胞中评估了CBD的神经保护作用。在分化的人Caco-2细胞(肠上皮细胞模型)中评估了CBD恢复炎症诱导的肠道通透性的能力。
(1)在增殖和汇合的SKOV-3细胞中,所有CBD样品均以浓度依赖性方式类似地降低了刃天青代谢,作为细胞活力的标志物(<0.001)。(2)在暴露于OGD的周细胞中,所有CBD样品在24小时时均类似地减少了细胞损伤(通过乳酸脱氢酶测量)31%-48%,并减少了炎症(通过IL-6分泌测量)30%-53%。对于所有CBD来源,5HT受体拮抗作用抑制了IL-6的减弱。(3)在暴露于炎症(TNFα和IFNγ,10 ng/mL,持续24小时)的分化Caco-2细胞中,与对照相比,每个CBD样品均提高了上皮通透性的恢复速度(<0.05-0.001),这被CB受体拮抗剂抑制。
我们的结果表明,纯化的天然与合成CBD在抗增殖、抗炎或通透性效应方面在体外没有药理学差异。在开发新的CBD药物时,应将CBD样品的纯度和可靠性以及最终药物制剂视为比CBD的起始来源更重要的因素。