About 2,200 people in England are diagnosed every year with the condition, making it the commonest form of brain cancer.
“We think that Sativex may kill glioblastoma tumour cells and that it may be particularly effective when given with temozolomide chemotherapy, so it may enhance the effects of chemotherapy treatment in stopping these tumours growing, allowing patients to live longer, said Susan Short, a professor of clinical oncology and neuro-oncology at Leeds University, who is the principal investigator of the study. “That is what we want to test in the study,” she said.
“It showed that this combination was safe, although some patients had problems with side-effects including sickness, tiredness and dizziness.
The Brain Tumour Charity plans to push ahead with the trial but stressed that doing so depended on the results of an appeal to help cover the £450,000 costs involved. It has suspended its usual programme of research grants after losing 25% of its income during the Covid-19 pandemic.
“The study was not designed to test whether Sativex was better in terms of survival. But it did suggest that some patients who had Sativex did better than expected and better than those who just had chemotherapy,” she said.
Professor Susan Short (pictured above), is the principal investigator on the new trial and Professor of Clinical Oncology and Neuro-Oncology at Leeds. She said: “The treatment of glioblastomas remains extremely challenging. Even with surgery, radiotherapy and chemotherapy, nearly all of these brain tumours re-grow within a year, and unfortunately there are very few options for patients once this occurs.
Almost all glioblastomas recur even after intensive treatment including surgery, radiotherapy and chemotherapy, and average survival is just 12-18 months from first diagnosis.
Tackling aggressive brain cancer
The trial will measure whether adding Sativex to chemotherapy extends the overall length of patients’ lives (overall survival), delays the progression of their disease (progression-free survival) or improves quality of life.
“We know there is significant interest among our community about the potential activity of cannabinoids in treating glioblastomas, and we’re really excited that this world-first trial here in the UK could help accelerate these answers. The recent early-stage findings were really promising and we now look forward to understanding whether adding Sativex to chemotherapy could help offer life-extension and improved quality of life, which would be a major step forward in our ability to treat this devastating disease.
“With so few treatments available and average survival still so heartbreakingly short, thousands affected by a glioblastoma in the UK each year are in urgent need of new options and new hope.
Glioblastoma (GBM) or WHO grade IV astrocytoma is the most aggressive form of brain tumors and ranks among the deadliest types of cancer. It is also the most common malignant primary brain tumor. Its high proliferation rate and invasiveness, together with a considerable cellular and molecular heterogeneity, is a challenge for treatment. Current therapeutic strategies include surgery, chemotherapy, radiotherapy and combinations thereof. Temozolomid (TMZ) is considered as the benchmark for treatment but resistance to TMZ antitumoral action is frequent and contributes to the overall poor prognosis. After second line treatment with TMZ, median survival is around 5.1 to 13 months, depending on the study .
Cannabinoids demonstrate tumor-specific cytostatic/cytotoxic effects modulating the growth of glioblastoma by multiple, often overlapping mechanisms that repeatedly showed synergism when combined with other treatments. In particular CBD has been reported to activate apoptosis via oxidative stress (increase in ROS production in tumor cells ), and to inhibit tumor cell proliferation by inducing cell cycle arrest. Furthermore, CBD inhibits tumor angiogenesis and infiltration/ invasion even at low concentrations and abrogates resistance of glioma stem-like cells to BCNU (carmustine) therapy . Cannabinoids are synergistic with chemotherapy and also with gamma-irradiation [7-9]. So far, experiments suggest that high doses of cannabinoids are necessary in order to achieve anti-tumor effects. In the inverse, low concentrations or doses respectively, may even enhance the growth of glioma, lung and breast cancer cells in vitro  and in vivo [11,12]. In addition to the tissue concentration and experimental conditions, effects depend very much upon the nature of the tumor cells. Although preclinical results cannot be transferred one-to-one to the situation in man, dose-dependency has been observed not only in vitro but also in animal experiments. A condensed overview on available in vivo results with CBD is presented in table 1.
What are the perspectives of cannabidiol (CBD) for the treatment of glioblastoma?
cannabidiol, CBD, cannabinoids, delta-9-tetrahydrocannabinol, THC, glioblastoma
Anti-cancer effects of cannabinoids have long been argued. Scientific evidence goes back to 1974 at the Medical College of Virginia at the behest of the US government. In an attempt to provide data proving a link between cannabis and cancer risk in order to provide evidence justifying international prohibition, the contrary was observed . With the detection of the endocannabinoid system in the early 90-ies, much insight was gained into the mechanisms of cannabinoids; a number of preclinical studies, in vitro as well as in vivo, confirmed the antineoplastic properties of both, phyto- and synthetic cannabinoids. Out of the phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best studied substances. These two cannabinoids differ in their effective doses: Common oral doses of THC are in the order of two to three times 2.5 mg to 10 mg/day, whereas CBD is currently administered in a dose of 100 to 300mg twice daily; doses up to 1,500mg CBD have been well tolerated. THC has some inherent clinical drawbacks due to its psychotropic properties, in addition to increased anxiety and withdrawal symptoms after high doses and down-regulation of CB1 receptors [3,4]. In contrast, CBD is free from such constraints. Furthermore, THC is unsuited for children and adolescents. Although rare when compared with adults, brain tumors are the most common solid tumors in children.
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