2021 Study Shows the Potential of CBG to Treat Glioblastoma
Glioblastoma (GB) is one of the most aggressive brain tumors in existence, and new treatments are desperately needed to improve prognoses for patients. Most of the research concerning phytocannabinoids and GB involve tetrahydrocannabinol (THC) and cannabidiol (CBD), the most prominent constituents of cannabis. Given that many other phytocannabinoids, like cannabigerol (CBG), have shown activity against various cancers, it is reasonable to start exploring their value in GB as well. Indeed, a new study in the journal Cells titled “Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma” demonstrated the effects of CBG, as well as CBD and THC, on the growth of GB cells.
Before examining combinations of different phytocannabinoids, each isolated compound was tested on established GB cell lines and GB cells derived from surgical biopsies. CBG and THC possessed similar potencies in reducing the viability of these cells, while CBD was about 20% more potent. The results were different when examining glioblastoma stem cells (GSCs), which are undifferentiated cells that contribute to resistance of GB tumors to conventional therapy. In this case, CBD and THC were similar in their viability-reducing potency, while CBG was substantially weaker. CBD was still slightly stronger than THC though, indicating it was the most effective phytocannabinoid at reducing viability in both GB cells and GSCs. Further experiments revealed the viability-lowering effect was likely due to induction of programmed cell death (apoptosis). Interestingly, GSCs were more sensitive to apoptosis induced by all the phytocannabinoids than the differentiated GB cells. In the chart below, U87 and NIB138 are GB cells, and NCH644 and K26 are GSCs.
Caspase-3, a key enzyme involved in apoptosis, was not increased substantially in GB cell lines in response to CBD or CBG, as reflected by the low apoptotic rates shown above. However, combining CBD and CBG massively increased caspase-3 activation. Temozolomide (TMZ), a standard chemotherapeutic agent for GB, also barely increased caspase-3 on its own, but when combined with CBD and CBG, levels of the enzyme were raised tremendously. However, CBG and CBD were more effective on their own than with TMZ in two of the three tested cell lines (U373 and T98), whereas the U87 cell line showed the highest caspase-3 expression when all three compounds were mixed. Therefore, CBG and CBD sometimes worked better on their own, but TMZ was always more effective when combined with phytocannabinoids than on its own.
Researchers also tested different combination ratios of CBD and CBG together to examine potential synergy against GB cells and GSCs. Interestingly, the optimal ratios were essentially reversed depending on the cell type. For GB cells, the optimal ratio reported was 1:4 CBD:CBG, while for GSCs it was 3:1 CBD:CBG. The addition of THC at low concentrations did not significantly enhance the effects of the CBD:CBG combinations, although at higher concentrations appeared to contribute some benefit. Ultimately, researchers stated, “We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy.”
Despite these observations, this study only used isolated phytocannabinoids, and the effects in humans using whole-plant cannabis extracts can be quite different. Extrapolating dosing from cell studies to humans is also difficult, but such studies do provide indications for what may work in further animal or human studies. It is too soon to say whether THC could be replaced by CBG for GB treatment, but this possibility is worth exploring, especially in patients who cannot tolerate the intoxicating nature of THC. The promise of using nonintoxicating phytocannabinoids to treat cancer is exciting, as more patients would be able to comply with high doses and more medical professionals would be open to using them.
