Medical Cannabis and the Hallmarks of Cancer: A Critical Narrative Review.

Russo D.; Fernandes R.; Tavares V.; Agrelo A.; Medeiros R. · International journal of molecular sciences · 2026

**Background & Methods** This is a narrative review synthesizing current evidence on medical cannabis and its potential anticancer mechanisms. The review frames cannabinoid effects, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), within the established hallmarks of cancer biology to identify therapeutic targets and mechanisms of action. **Key Findings** • CBD demonstrates antiproliferative effects through modulation of multiple oncogenic signalling pathways (EGFR, PI3K/AKT, RAS/RAF/ERK, mTOR, Wnt/β-catenin) and activation of tumour suppressor pathways (p53, p21, p27), resulting in cell cycle arrest and programmed cell death via mitochondrial dysfunction and autophagy. • Cannabinoids exhibit anti-invasive, antiangiogenic, and immunomodulatory properties with emerging evidence suggesting interactions with the tumour microenvironment and microbiome, supporting activity across multiple cancer hallmarks. • While preclinical evidence suggests biologically plausible antitumour activity, medical cannabis has primarily been used clinically for supportive oncology care rather than direct anticancer treatment, indicating a significant gap between laboratory findings and clinical application. **Dosage & Administration** Not reported. The review focuses on preclinical mechanisms rather than clinical dosing protocols. **Safety & Adverse Effects** Not reported. Safety profiles and adverse effects are not detailed in this mechanism-focused narrative review. **Evidence Quality** This narrative review is predominantly limited by its reliance on preclinical evidence, representing a lower level of clinical evidence (Level 5). The authors explicitly acknowledge that current understanding remains largely preclinical, with minimal clinical trial data available. Significant limitations include the lack of robust translational studies bridging laboratory findings to human applications, unclear pharmacokinetic and pharmacodynamic profiles in cancer patients, and absence of established clinical efficacy and safety data. The heterogeneous nature of cancer and variability in cannabinoid composition across products further complicate interpretation. The authors conclude that while cannabinoids present promising candidates for combination therapeutic strategies, rigorous clinical trials are essential to validate findings, determine appropriate dosing, assess safety profiles, and establish efficacy before integration into multimodal cancer treatment protocols can be recommended.

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