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Research Review: Using Cannabinoids to Treat Glioma

At Radicle Health, we’re seeing an increase of glioma patients who are considering cannabis as a treatment modality. Finding—and trusting—information about using cannabis to treat glioma can be challenging, especially for a condition as unsettling as a brain tumor.


Glioma is a category of brain and spinal cord tumors that occur in glial cells. Glial cells are brain cells that support nerve cells. There are four grades of glioma, each comprised of different types of cells and each requiring unique treatment strategies. Glioblastoma multiforme (GBM) is a grade IV glioma and is the most aggressive and fast-growing brain tumor. These tumors can occur at any age but tend to appear in older adults and can cause headaches, nausea, vomiting, and seizures. GBM is very difficult to treat and most GBM patients have a poor prognosis—fewer than 5% of patients diagnosed with GBM survive 5 years past initial diagnosis.[1]


GBM tumors can contain self-renewing cells that are similar to stem cells. These glioma stem-like cells (GSCs) can account for the high resistance to therapy and high rates of tumor recurrence in GBM patients. The standard treatment for GBM includes the surgical removal of the tumor, radiation therapy, and chemotherapy with temozolomide (TMZ). TMZ is an oral chemotherapy drug.[2]


Presently, GBM remains incurable. Novel treatments (and specifically treatments targeting the population of GSCs) are urgently needed to improve quality of life and survival rates of the patients suffering from GBM.


Accumulating evidence indicates that cannabinoids have potent anti-tumor characteristics and might be used successfully in the treatment of GBM.[3] For example, a study completed in Spain in 2006 with nine terminally ill glioma patients[4] demonstrated that THC reduced tumor cell proliferation and was well tolerated.


Gliomas rarely metastasize. However, these glioma cells can successfully spread into adjacent, healthy brain tissue.[5] Consequently, the management of GMB relies on developing and implementing strategies that inhibit the migration GBM cells. And while the role of cannabinoids in GBM migration remains poorly understood, evidence from studies completed in test tubes and in animal models suggests that cannabinoids, especially CBD, can prevent the spread of glioma cells.[6] [7]


Studies have demonstrated enhanced anti-tumor effects with THC and CBD combinations.[8] The therapeutic potential of THC:CBD combinations was furthermore enhanced when combined with standard GBM chemotherapy, such as with TMZ or with radiation therapy. For example, one study with mice demonstrated enhanced reduction of tumor size with co-administration of THC, CBD, and TMZ in comparison to the effects of THC, CBD, and TMZ alone.[9]


The success demonstrated in preclinical models prompted GW Pharmaceuticals to study these combinations in a placebo-controlled clinical trial using their oromucosal spray product (called Sativex, which is a 1:1 THC:CBD mixture) in combination with TMZ in 21 GBM patients.[10] All patients were documented with recurrent GBM. Patients receiving cannabis were administered 2.7mg THC and 2.5mg CBD per spray with a maximum of 12 sprays per day.[11] The group that was treated with Sativex and TMZ had an 83% one-year survival rate. The control group received TMZ only and had a 53% 1-year survival rate. The Sativex formula was generally well tolerated (adverse effects caused 2 patients from each group to discontinue).[12]


In very recent preclinical glioma models [13] (including models derived from GSCs), researchers confirmed that the antitumoral effect was stronger when TMZ was administered with a cannabinoid combination containing a higher proportion of CBD. The administration of THC and a higher proportion of CBD in combination with TMZ reduced tumor growth and increased animal survival at a higher extent than treatment with THC:CBD at a 1:1 ratio in combination with TMZ.[14]

Research in pre-clinical and clinical models demonstrate that cannabinoids produce anti-tumor effects in GBM by promoting programmed cell death, reducing blood vessel formations in tumors, and by reducing the spread of and the replication of cancerous cells. New research now demonstrates that cannabinoid efficacy can be enhanced by combining chemotherapeutic agents and might lead to improved therapeutic strategies against GBM and other diseases of the nervous system.


And remember—you should always get your medical advice from a healthcare professional (HCP), especially if you have a condition as serious as a glioma. A competent healthcare professional (HCP) will provide a comprehensive intake meeting where you review your condition and assess your prescription medications to identify potential contraindications with cannabis. Use your time with your HCP to learn how to administer your medicines, how to use any new devices, and discuss the benefits and potential side effects of any recommended products. And, ensure that you work with a HCP that provides ongoing support to help you navigate the complexities of cannabis treatment, local laws, and access issues.


Some patients skip this step because it can be expensive, and insurance companies do not cover these costs. However, working with an HCP can be an effective way to save time and money. An experienced HCP can get you started with a treatment plan that includes specific products, dosing, and frequency information, and can save you the heartache and expense of false starts and bad advice.




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Sources:

[1] https://academic.oup.com/neuro-oncology/article/16/suppl_4/iv1/1047153

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964193/

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964193/

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796096/

[6] https://www.ncbi.nlm.nih.gov/pubmed/23243024/

[7] https://www.ncbi.nlm.nih.gov/pubmed/24204703/

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054289/

[9] https://www.ncbi.nlm.nih.gov/pubmed/21220494

[10] https://clinicaltrials.gov/ct2/show/NCT01812603

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964193/

[12] https://www.gwpharm.com/about-us/news/gw-pharmaceuticals-achieves-positive-results-phase-2-proof-concept-study-glioma

[13] https://www.sciencedirect.com/science/article/abs/pii/S0006295218303897

[14] https://sci-hub.tw/10.1016/j.bcp.2018.09.007

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