Cannabidiol impairs tumor-associated behaviors and modulates apoptosis- and autophagy-related pathways in cisplatin-resistant head and neck squamous cell carcinoma.

de Melo E.; Almeida J.; Pires A.; Ribeiro R. · Medical oncology (Northwood, London, England) · 2026

**Background & Methods** This review evaluated the antitumor effects of cannabidiol (CBD) in cisplatin-resistant, HPV-negative head and neck squamous cell carcinoma (HNSCC) using in vitro cell models (HN13 cells), biochemical assays, and in vivo chorioallantoic membrane (CAM) models. Multiple endpoints were assessed including cytotoxicity, migration, invasion, apoptosis, autophagy, and synergistic effects when combined with cisplatin. **Key Findings** • CBD demonstrated selective cytotoxicity against HN13 cancer cells compared to normal fibroblasts and keratinocytes, while reducing migration, invasion, matrix metalloproteinase-2/9 activity, clonogenic survival, and 3D spheroid growth. • CBD modulated cell death pathways by altering apoptosis and autophagy-related proteins; pharmacological autophagy inhibition (3-MA) enhanced CBD-induced apoptotic signaling, increasing PARP and caspase-3 cleavage, indicating interdependent pathway regulation. • In vivo CAM studies showed CBD reduced tumor growth and vascular area without inducing vascular irritation, and CBD exhibited synergistic cytotoxic effects when combined with cisplatin in resistant HN13 cells. **Dosage & Administration** Not reported. The abstract does not specify the concentrations, doses, or administration routes of CBD used in the experimental protocols. **Safety & Adverse Effects** CBD did not induce vascular irritation in the HET-CAM assay, demonstrating acceptable vascular safety in the in vivo model tested. Specific systemic adverse effects or toxicity profiles were not detailed in the available abstract. **Evidence Quality** This study represents preclinical research with significant limitations. Findings are derived from in vitro cell culture systems and avian models (CAM), which have limited translational relevance to human HNSCC. The study lacks clinical data, human subject evaluation, and pharmacokinetic characterization. As a review article published in 2026, assessment of peer review quality cannot be determined from the abstract alone. The evidence level is preclinical/laboratory-based, supporting only exploratory investigation rather than clinical application. Generalizability to HPV-positive HNSCC and other cancer types remains unclear. Future clinical trials are required to establish safety, efficacy, and optimal dosing in human patients with chemoresistant HNSCC.

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