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

Glioblastoma (GBM) remains one of the most lethal brain tumors, with current therapies offering limited benefits and high relapse rates. This study presents the first preclinical evidence that pretreatment with inhaled cannabidiol (CBD) before tumor establishment can markedly inhibit GBM progression. We hypothesized that early CBD exposure could prime the immune and molecular landscape to resist tumor growth. C57BL/6 mice were pretreated with inhaled CBD for 3 or 14 days, or with placebo, prior to intracranial implantation of glioblastoma cells. Tumor growth, immune checkpoint expressions (IDO, PD-L1), and key biomarkers (MGMT, Ki67) were analyzed to evaluate tumor dynamics and immune modulation. Fourteen-day CBD pretreatment significantly reduced tumor burden compared with both placebo and 3-day CBD groups, accompanied by decreased IDO, PD-L1, MGMT, and Ki67 expression, which are signatures of a less aggressive tumor phenotype. These findings suggest that prolonged CBD exposure can precondition the tumor microenvironment toward an anti-tumor state, improving disease control and potentially lowering relapse risk. This study introduces a novel concept of CBD pretreatment as an immune-modulatory strategy with high translational potential for glioblastoma management.