Synergistic Effects of Cannabinoids and Chemotherapeutics

Synergies between Δ⁹-tetrahydrocannabinol or cannabidiol and gemcitabine, cisplatin, or a combination of gemcitabine/cisplatin were studied using the checkerboard assay in T24 cells. Synergy was also assessed between Δ⁹-tetrahydrocannabinol or cannabidiol and cannabivarin or cannabichromene. Briefly, the synergy assay was performed with 3000 cells in 96-well plates with a final volume of 100 μL per well. Cannabinoid concentrations ranged from 0 to 10 mM and gemcitabine and cisplatin concentrations between 0 and 100 mM. Fluorescence was quantified as described before using alamar Blue® after 48-h treatment. The analysis was performed using SynergyFinder 2.0 (Ianevski et al. 2020 (link)), where the Bliss independence drug interaction model was used. A synergy score of <  − 10 was considered as antagonistic, a range from − 10 to + 10 as additive, and >  + 10 as synergistic (Ianevski et al. 2020a (link); 2020b (link)). Drug combination responses were also plotted as concentration–response curves using GraphPad Prism software and were used to determine statically significant and synergistic combinations.