Cannabinoids in oncology: pharmacology, clinical applications, and translational perspectives

Cannabis and cannabinoid products are increasingly used by patients with cancer for symptom management and supportive care. Although cannabis is widely used to alleviate cancer- and treatment-related symptoms, many patients also believe that it possesses direct anticancer activity. This review provides a comprehensive pharmacologic and clinical assessment of cannabinoids in oncology, integrating the endocannabinoid system, cannabinoid receptor signaling, pharmacokinetics, therapeutic applications, adverse effects, drug-drug interactions, and emerging antitumor research. The strongest clinical evidence supports selected cannabinoid preparations for refractory chemotherapy-induced nausea and vomiting, whereas evidence for cancer-related pain, appetite stimulation, sleep disturbance, anxiety, and opioid-sparing effects remains limited or inconsistent. Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) differ substantially in receptor pharmacology, psychoactive effects, metabolism, and toxicity, with important implications for product selection, dosing, and interactions with anticancer and supportive-care medications. Preclinical studies demonstrate antiproliferative, proapoptotic, antiangiogenic, and immunomodulatory effects across multiple tumor models; however, cannabinoid signaling is highly context dependent and may also promote tumor progression in selected settings. Human evidence for direct anticancer activity remains sparse, consisting predominantly of small early-phase studies and observational data, with no established improvement in tumor response, progression-free survival, or overall survival. Particular caution is warranted regarding neuropsychiatric and cardiovascular toxicity, pharmacokinetic drug interactions, and the potential influence of cannabis on immune checkpoint inhibitor outcomes. Overall, cannabinoids have defined but limited roles in supportive oncology, while their direct antitumor potential remains investigational. Future studies should prioritize standardized formulations, pharmacologically informed dosing, rigorous randomized designs, clinically meaningful endpoints, and biomarker-based approaches to define therapeutic benefit and risk.