Gliomas are a type of brain and spinal cord tumor that arise from glia, the cells that directly support the function of neurons. This type of cancer is highly invasive and follows characteristic patterns, typically invading adjacent brain structures nearby large blood vessels via a process called angiogenesis (the formation of new blood vessels). In clinical and preclinical studies, cannabinoids have been shown to hinder the progression of gliomas by reducing tumor growth, inducing cell death, providing synergistic effects with radiotherapy, and by inhibiting angiogenesis and metastasis (spreading to other areas) of tumor cells. Some of these effects are thought to be mediated by the body’s endocannabinoid system (ECS), a group of receptors found on the surface of the cell membrane and mitochondria, while others occur through non-cannabinoid receptor interactions.
Reductions in Cancer Spread: Multiple studies have shown that cannabidiol (CBD) is capable of reducing the invasiveness of gliomas in a concentration dependent fashion. These effects do not appear to be mediated by cannabinoid receptors and seem to arise through multiple processes. One factor is CBD’s ability to inhibit the migration of cancer cells. Additionally, CBD reduces invasiveness through a decrease in the production of pro-angiogenic factors. These pro-angiogenic factors are proteins that promote the formation of new blood vessels, many of whose levels have shown to be directly correlated with cancer invasiveness[ref]Vaccani A, Massi P, Colombo A, Rubino T, Parolaro D. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. Br J Pharmacol. 2005;144(8):1032-6[/ref].
Inducing Death of Cancer Cells: Researchers from Spain have demonstrated the ability of THC to induce cell cancer death through such cannabinoid receptor dependent mechanisms. Specifically, the THC causes a stress response in glioma cells that leads to the accumulation of a compound called ceramide, a compound that ultimately leads to apoptosis (programmed cell death)[ref]Sánchez C, Galve-roperh I, Canova C, Brachet P, Guzmán M. Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Lett. 1998;436(1):6-10.[/ref].
This stress response kills only the cancerous cells, leaving the healthy cells unharmed. Studies using CBD have also shown its ability to kill glioma cells by increasing the production of compounds called reactive oxygen species (ROS). These ROS are a by-product of cellular respiration, the process of energy production in the form of ATP that occurs in the mitochondria. Increased levels of these molecules put additional stress on the cell and cause signaling cascades that ultimately lead to similar cell death mechanisms[ref]Massi P, Vaccani A, Bianchessi S, Costa B, Macchi P, Parolaro D. The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. Cell Mol Life Sci. 2006;63(17):2057-66[/ref].
Antiproliferative Effects: In addition to inhibiting the spread of cancerous cells, cannabinoids have also been shown to induce cell cycle arrest, effectively hindering their division. Researchers have demonstrated that the administration of THC and CBD together causes synergistic effects in this curbing cancer cell proliferation[ref]Marcu JP, Christian RT, Lau D, et al. Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther. 2010;9(1):180-9[/ref].
Based on these studies cannabinoids hold much therapeutic value for the treatment of gliomas due to their antitumoral action, ability to kill cancer cells, and effects on proliferation. Additionally, studies in mouse models using both THC and CBD have also been shown to have an additive effect when used in conjunction with radiotherapies, suggesting that cannabinoids could potentially enhance current cancer mitigation strategies[ref]Scott KA, Dalgleish AG, Liu WM. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther. 2014;13(12):2955-67[/ref].