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Background <p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest and most treatment-resistant cancers, with limited progress in improving patient survival. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential anticancer agent due to its diverse molecular effects in preclinical cancer models.</p> Objective <p>This systematic review aims to evaluate the preclinical and early clinical evidence regarding CBD’s anticancer effects in PDAC, with emphasis on its molecular mechanisms, therapeutic synergies, and translational feasibility.</p> Methods <p>We systematically searched PubMed, Scopus, Web of Science, EMBASE, and Google Scholar (2006–2025) for studies examining the effects of CBD on PDAC in vitro, in vivo, and in clinical contexts. Studies were assessed for methodological quality and relevance to CBD-related antitumor activity.</p> Results <p>Fifteen studies met the inclusion criteria, including in vitro, animal, and limited clinical investigations. CBD exhibited antitumor properties via multiple pathways, such as CerS1-mediated ER stress and apoptosis, GPR55/MAPK inhibition, immune modulation, and chemosensitization to gemcitabine. Combination therapies (CBD with cannabinoids or chemotherapeutics) enhanced therapeutic outcomes in preclinical models. However, clinical evidence remains preliminary and insufficient to establish efficacy.</p> Conclusion <p>CBD demonstrates promising anticancer potential in PDAC through diverse molecular mechanisms and synergistic effects with chemotherapy. Nonetheless, significant translational barriers—including formulation variability, pharmacokinetics, and a lack of clinical trials—must be addressed. Further studies are warranted to validate these findings in human settings.</p>

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Cannabidiol in pancreatic ductal adenocarcinoma: preclinical evidence, molecular mechanisms, and translational challenges

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月19日

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  • Mojtaba Esmaeli,
  • Maryam Dehghanpour Dehabadi,
  • Ali Asghar Khaleghi

摘要

Background

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest and most treatment-resistant cancers, with limited progress in improving patient survival. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential anticancer agent due to its diverse molecular effects in preclinical cancer models.

Objective

This systematic review aims to evaluate the preclinical and early clinical evidence regarding CBD’s anticancer effects in PDAC, with emphasis on its molecular mechanisms, therapeutic synergies, and translational feasibility.

Methods

We systematically searched PubMed, Scopus, Web of Science, EMBASE, and Google Scholar (2006–2025) for studies examining the effects of CBD on PDAC in vitro, in vivo, and in clinical contexts. Studies were assessed for methodological quality and relevance to CBD-related antitumor activity.

Results

Fifteen studies met the inclusion criteria, including in vitro, animal, and limited clinical investigations. CBD exhibited antitumor properties via multiple pathways, such as CerS1-mediated ER stress and apoptosis, GPR55/MAPK inhibition, immune modulation, and chemosensitization to gemcitabine. Combination therapies (CBD with cannabinoids or chemotherapeutics) enhanced therapeutic outcomes in preclinical models. However, clinical evidence remains preliminary and insufficient to establish efficacy.

Conclusion

CBD demonstrates promising anticancer potential in PDAC through diverse molecular mechanisms and synergistic effects with chemotherapy. Nonetheless, significant translational barriers—including formulation variability, pharmacokinetics, and a lack of clinical trials—must be addressed. Further studies are warranted to validate these findings in human settings.