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

Gutiérrez-Iñiguez C.; Olivas-Aguirre M.; Pottosin I.; Dobrovinskaya O. · Biomolecules · 2026

**Background & Methods** This review examined the dose-dependent effects of cannabidiol (CBD) on human natural killer (NK) cell viability and antitumor properties. The study evaluated CBD cytotoxicity mechanisms in NK cells and assessed the impact of CBD pretreatment on NK cell-mediated killing of leukemic Jurkat target cells using co-culture models. **Key Findings** - CBD demonstrated dose-dependent cytotoxicity against NK cells with an IC50 of 77 μM at 24-48 hours; concentrations up to 10 μM were safe, while concentrations above 30 μM induced cell death. - CB1 receptor antagonism partially reversed CBD cytotoxicity, whereas CB2 antagonism was ineffective, suggesting CB1-mediated mechanisms; cyclosporin A (an mPTP inhibitor) strongly suppressed cytotoxicity, indicating mitochondrial permeability transition pore involvement. - NK cell antitumor function showed donor-dependent variability: 50% of donors maintained maximal cytotoxicity against Jurkat cells following pretreatment with up to 25 μM CBD, while the other 50% experienced 60% reduction in NK cytotoxicity regardless of CBD concentration. **Dosage & Administration** CBD concentrations tested: up to 10 μM (safe range); 30 μM and above (cytotoxic); pretreatment doses up to 25 μM for functional assays. Incubation period: 24-48 hours. Route of administration not specified. **Safety & Adverse Effects** At concentrations above 30 μM, CBD induced NK cell death through mitochondrial depolarization mechanisms dependent on CB1 receptor signaling and mPTP opening. Cyclosporin A sensitivity indicated potential mitochondrial dysfunction. No adverse effects reported at concentrations up to 10 μM in NK cells. **Evidence Quality** This is a review article synthesizing experimental findings rather than a primary research study, limiting definitive conclusions. The study demonstrates significant donor-dependent variability in NK cell response to CBD, which substantially complicates clinical application. The apparent IC50 of 77 μM may exceed therapeutically relevant concentrations, though overlap exists with palliative dosing ranges. Limitations include in vitro methodology, lack of human pharmacokinetic data to correlate in vitro concentrations with achievable serum levels, and absence of mechanistic clarity regarding donor-dependent variability. The findings suggest careful individualized assessment is necessary before incorporating CBD into anticancer immunotherapy protocols.

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