Cannabidiol as a Prophylactic Agent Against Glioblastoma Growth: A Preclinical Investigation

Purpose: Glioblastoma (GBM) is one of the most aggressive brain tumors, with limited treatment options and poor outcomes due to frequent relapse after surgery. This study aims to investigate whether pretreatment with inhaled cannabidiol (CBD) can inhibit GBM growth in a preclinical murine model. Specifically, we hypothesize that CBD pretreatment may reduce tumor progression and modulate the tumor microenvironment. Methods: C57BL/6 mice were pretreated with inhaled CBD for either 3 or 14 days, or a placebo, followed by intracranial implantation of glioblastoma cells. Tumor growth, immune checkpoint expression (IDO/PD-L1), and key biomarkers (MGMT/ Ki67) were assessed to determine the impact of CBD pretreatment on tumor progression and the immune microenvironment. Results: The 14-day CBD pretreatment significantly reduced tumor growth compared to both the placebo and 3-day CBD groups. Additionally, this group showed lower expression of immune checkpoints (IDO, PD-L1) and reduced levels of MGMT and Ki67, suggesting enhanced tumor suppression. These results indicate that prolonged CBD pretreatment modulates the tumor microenvironment and may improve tumor control and reduce relapse risk. Conclusion: This study demonstrates that inhaled CBD pretreatment significantly inhibits GBM growth in a preclinical model. CBD ability to reduce immune checkpoint expression and key biomarkers associated with tumor progression suggests that it could be an effective strategy for enhancing the efficacy of GBM therapies and potentially improving post-surgical outcomes. Further research is required to investigate its clinical potential and mechanisms of action.