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

Warter U.; Yogev Y.; Nwobodo D.; Lialin K.; Mantin D.; Meirovitz M.; Meijler M.; Mayer A. · ACS omega · 2026

**Background & Methods** This review and experimental study evaluated the pharmacological properties of two phytocannabinoids—THC and CBD—as potential antitumor agents against epithelial ovarian cancer (EOC) using three established EOC cell lines. The researchers conducted RT-qPCR analysis, in silico modeling, and combination studies examining cannabinoid efficacy alone and in conjunction with carboplatin, the standard chemotherapeutic agent for ovarian cancer. **Key Findings** • Both THC and CBD demonstrated intrinsic antiproliferative activity against EOC cell lines; however, CBD monotherapy significantly outperformed combinations of CBD with THC, challenging the theoretical "entourage effect" in an oncological context. • Molecular analyses revealed low expression of classical cannabinoid receptors (CB1/CB2) on EOC cells, suggesting that observed antiproliferative effects are primarily mediated through receptor-independent mechanisms rather than traditional signaling pathways. • Most critically, concurrent administration of cannabinoids with carboplatin paradoxically reduced the chemotherapeutic efficacy of the platinum agent, indicating a potentially harmful drug-drug interaction that could compromise standard ovarian cancer treatment outcomes. **Dosage & Administration** Not reported. The study employed in vitro cell culture models without specified human dosing parameters or clinical administration protocols. **Safety & Adverse Effects** Not reported. The study focused on efficacy and pharmacological interactions rather than adverse effect profiling. However, the paradoxical inhibition of carboplatin efficacy represents a significant safety concern regarding cannabinoid-chemotherapy combinations. **Evidence Quality** This is a preliminary in vitro study with substantial limitations. The research was conducted exclusively in cell culture models without animal or human clinical data, limiting direct translational applicability. The findings are hypothesis-generating rather than definitive. The authors acknowledge that mechanistic understanding of cannabinoid-chemotherapy interactions remains incomplete. The study's primary strength is raising an important cautionary signal about potential harmful interactions between cannabis and platinum-based chemotherapy. The authors appropriately call for larger, more robust clinical studies before cannabis use can be recommended alongside conventional EOC treatment. The low receptor expression findings warrant investigation into alternative molecular mechanisms. Overall, while provocative, these results represent early-stage evidence requiring substantial validation before clinical implementation.

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