The Effect of Cannabidiol on the Viability and Anticancer Properties of Human NK Cells: Consequences for Therapies

The palliative and anti-cancer properties of CBD are attracting increasing attention. We have examined the dose-dependent effects of CBD on the viability and antitumor properties of human NK cells. CBD killed NK cells with an apparent IC50 of 77 μM at 24–48 h of incubation. Concentrations up to 10 μM caused neither cell death nor a significant decrease in metabolic activity, whereas concentrations above 30 μM provoked cell death. The antagonist of CB1 partly reverted CBD cytotoxicity, whereas the antagonist of CB2 was inefficient. Cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore, mPTP, strongly suppressed the CBD cytotoxicity. CBD produced the CsA-sensitive depolarization of mitochondrial membrane potential in leukemic Jurkat cells, with a lesser effect on NK cells. The cytotoxicity of NK cells against Jurkat cells was evaluated in a 1:1 co-culture. Different donors displayed greatly variable NK cells’ degranulation, which was unaffected by a pre-treatment with up to 25 μM of CBD. NK cells from half of the tested donors displayed maximal cytotoxicity against target cells upon pretreatment with up to 25 μM of CBD, whereas in others, NK cytotoxicity decreased by 60%. Therefore, the appropriateness of including CBD in anticancer treatment should be carefully assessed based on the concentrations expected for palliative or antitumor effects.