In this April 2023 case report, a 36-year-old woman was diagnosed with glioblastoma multiforme, an aggressive form of grade 4 brain cancer. With a median survival of 15 months, glioblastoma multiforme is the most aggressive malignant tumor overall and considered to be "incurable." After undergoing a partial removal of the brain tumor, the patient chose to decline conventional therapy, which involved a combination of radiotherapy and temozolomide-based chemotherapy. Instead, the patient used a combination of high dose medicinal cannabis (with high doses of both THC and CBD), melatonin, and oxygen/ozone therapy. A 2cm mass that was visible in 2016 had disappeared within a year.
Not only did this unconventional treatment result in a complete and long-lasting cure of the disease, but the treatment was also well-tolerated by the patient with no side effects. Seven years after her diagnosis, the patient is considered totally cured, suggesting this unconventional treatment could be a possible future direction in glioblastoma multiforme management.
The patient received supportive therapy that included oxygen-ozone (O2O3) therapy, melatonin, and medical cannabis (THC and CBD). The patient received medical cannabis products with an initial dose of 50mg of a product with 9% CBD (Bedrolite) and 100mg of a 22% THC (Bedrocan) product taken four times daily. Over time, she increased the dosage to 1 to 5 grams (1000-5000mg) per day of each THC and CBD product.
The patient received oxygen-ozone therapy, which involved rectal administration of a volume of 2.5 mL/kg of oxygen-ozone (97% oxygen, 3% ozone), at a concentration of 80 µg/mL, for two daily administrations (interval of six hours) for four consecutive days per week during the first month. For the next two months, the treatment involved a daily administration for four consecutive days per week. The patient then discontinued the therapy for three months after completing the first three months of oxygen-ozone therapy. The therapy was then restarted and maintained until the patient's current condition. The weekly sessions were reduced from four to two, and alternated between three months of treatment and three months off.
Melatonin was administered orally, starting at 100 mg once a day and increased to a maximum of 2g per day.
This case report adds to the growing body of evidence that cannabinoids found in the cannabis plant have the potential to be a valuable tool in the treatment of cancer.
The effects of cannabinoids in hindering tumor progression have been deeply investigated at preclinical levels, and two clinical trials further support their potential effects in glioblastoma multiforme. Additionally, oxygen-ozone therapy, which is widely used in several pathological conditions characterized by chronic inflammatory processes and immune overactivation, has potential benefits in glioblastoma multiforme treatment. Melatonin has antioxidant effects, and its potential role in tumor treatment has been investigated through various studies.
The ability of cannabinoids to kill cancer cells was first reported in 1975, and since then, several investigations have uncovered interesting findings about their mechanisms of action, pathways involved in their effects, and their safety and tolerability.
Phytocannabinoids like THC and CBD interact with cannabinoid receptors 1 and 2 (CB1 and CB2), as well as many other receptor sites, including other G-protein-coupled receptors, opioid and serotonin receptors, and transient receptors potential channels. The analysis of glioblastoma multiforme cell lines, ex vivo primary tumor cells, and glioblastoma multiforme tissue biopsies showed that glioblastoma multiforme tumors express both cannabinoid receptors, with high-grade tumors expressing high levels of CB2. On this basis, several in vitro and in vivo studies have investigated different phytocannabinoids for anti-tumor activity in glioma.
Clinical trials have analyzed the safety and tolerability of nabiximols, a cannabinoids-based oromucosal spray, administered in combination with dose-intense TMZ (chemo treatment) in patients with recurrent glioblastoma multiforme, as well as patients’ progression-free survival at 6 months and overall survival at 1 year. A phase II randomized clinical trial assessed the tolerability of two different ratios of medicinal cannabis in patients with high-grade gliomas, showing that its administration is safe, well-tolerated, and capable of providing symptomatic relief to patients.
The inhibition of tumor growth derives from different mechanisms consisting of the induction of cancer cell death by apoptosis, the inhibition of cancer cell proliferation, the impairment of tumor angiogenesis, and the blocking of invasion and metastasis.
After the first cycle of oxygen-ozone therapy, the 2cm residual tumor mass was no longer visible on the brain magnetic resonance imaging. The patient underwent quarterly visits, clinical-instrumental checks, and monthly blood and biochemistry tests. The MRIs done in subsequent periods confirmed that the morphological picture remained stable, and the patient was considered cured.
The case report also discusses the potential benefits of melatonin as a supportive therapy. Melatonin stimulates the production of cytokines and increases T helper immune responses. It also has retinal functions and antioxidant actions that contribute to its immunoenhancing effects, indirectly reducing nitric oxide formation and facilitating a decrease in the inflammatory response. A meta-analysis has shown that melatonin exerts a positive influence on tumor therapeutic strategies, exhibiting improvements in tumor remission and reducing chemotherapy-induced side effects.
The patient's treatment was successful, and she is considered to be completely cured seven years after her glioblastoma multiforme diagnosis. While more clinical studies are needed to verify the efficacy of this therapy for glioblastoma multiforme and other tumors, the patient's progress provides an encouraging result. The use of medical cannabis and phytocannabinoids for anti-tumor activity in glioma has been extensively studied, with promising results shown in preclinical and clinical studies. Further research in this area could lead to novel therapies for glioblastoma multiforme and other malignancies. It is heartening to know that the patient in this case report is still alive today, and the use of unconventional treatments provides hope for patients with glioblastoma multiforme and other cancers.
Despite resistance and skepticism around the use of cannabis in cancer treatment, a growing body of research suggests that cannabinoids like THC and CBD have powerful anti-tumor effects with few side effects. Recent studies have continued to demonstrate the therapeutic properties of cannabinoids in cancer treatment, suggesting that phytocannabinoids may hold promise as a cure for various types of cancer. The remarkable outcome of this case serves as encouragement to investigate cannabinoid-based therapies for glioblastoma more deeply, and may suggest that it could be a more efficient and safer treatment option than traditional chemotherapy. As research continues, cannabinoid-based therapies seem to be on the positive path to becoming a mainstream treatment option for cancer patients.
In conclusion, this case report suggests that oxygen-ozone therapy, melatonin, and a high dose cannabis combination of THC and CBD, can be considered a valid supportive treatment for glioblastoma multiforme and other tumors. It is also important to note that the patient remained without disease progression during the time of the therapy and did not develop side effects during treatments.
Study Title: The Effects of a Combination of Medical Cannabis, Melatonin, and Oxygen–Ozone Therapy on Glioblastoma Multiforme: A Case Report
Study Link: https://www.mdpi.com/2571-841X/6/2/22