Evaluation of Phytocannabinoids as Antitumor Agents against Ovarian Cancer Cells in Combination with Carboplatin.

Ovarian cancer is the second leading cause of death from gynecologic malignancy worldwide. The integration of phytocannabinoids into oncological care has outpaced our mechanistic understanding of their interactions with frontline chemotherapeutics. In this study, we provide a detailed pharmacological evaluation of two phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as antineoplastic agents against three epithelial ovarian cancer (EOC) cell lines. Using established EOC cell models, we demonstrate that both cannabinoids exhibit intrinsic antiproliferative activity, but CBD monotherapy significantly outperforms CBD-THC combinations. Furthermore, RT-qPCR and in silico analyses revealed a low density of classical receptors, indicating that cannabinoid efficacy in EOC may be primarily driven by receptor-independent mechanisms. Most importantly, we report that the coadministration of cannabinoids with carboplatin, the standard of care for EOC, paradoxically inhibits the platinum agent's antineoplastic efficacy. Our results challenge the "entourage effect" in an oncological context and provide a necessary cautionary framework for the use of cannabinoids alongside specific platinum-based regimens. Given the increasing use of cannabis among cancer patients, further robust studies examining interactions between cannabis and conventional chemotherapeutic agents are required to better evaluate safety and therapeutic efficacy in EOC treatment.