The Cytotoxic Effects of Cannabidiol and Cannabigerol on Glioblastoma Stem Cells May Mostly Involve GPR55 and TRPV1 Signalling

In glioblastoma (GBM), the highest-grade IV glioma, members of the large membrane receptor family of G protein-coupled receptors (GPCRs) are upregulated including CB1 and GPR55 that along with non-selective ion transporter protein TRPV1 bind endocannabinoids and phytocannabinoids with different affinities and signalling effects. The receptors are part of the endocannabinoid system (ECS) and are overexpressed in glioma to raise cancer defence signalling by ESC in tumour cells. We demonstrated that GPR55 and TRPV1 genes, but not CB1/CNR1 genes, correlated to GBM stem cell (GSC) gene markers, and both were highly expressed in GSCs compared with differentiated GBM cells. Therefore, we propose that GPR55 and TRPV1 receptors are the best targets for the antagonistic cannabinoids CBD and CBG (in an optimized mixture) to eliminate GBM stem cells. This approach avoids using psychoactive THC, which is potentially harmful, particularly in older GBM patients, and should be further tested in animal experiments and clinical trials