Findings from a new study examining human and canine brain cancer cells suggest that cannabidiol could be a useful therapy for a difficult-to-treat brain cancer The ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) in medicinal cannabis has shown to play a crucial role in improving the physical and functional wellbeing of brain cancer patients, according to newly published findings in a trial funded by BioCeuticals, the practitioner-only arm of Blackmores. World-first trial tests cannabis-based drug on aggressive brain tumours A major UK trial of cannabis-based drug Sativex in treating the most aggressive form of brain tumour is to launch at 15 NHS
CBD Shows Promise for Fighting Aggressive Brain Cancer
Newswise — Bethesda, MD – Findings from a new study examining human and canine brain cancer cells suggest that cannabidiol could be a useful therapy for a difficult-to-treat brain cancer. Cannabidiol, or CBD, is a non-psychoactive chemical compound derived from marijuana.
The study looked at glioblastoma, an often-deadly form of brain cancer that grows and spreads very quickly. Even with major advancements in treatment, survival rates for this cancer have not improved significantly.
“Further research and treatment options are urgently needed for patients afflicted by brain cancer,” said Chase Gross, a student in the Doctor of Veterinary Medicine/Master of Science program at Colorado State University. “Our work shows that CBD has the potential to provide an effective, synergistic glioblastoma therapy option and that it should continue to be vigorously studied.”
Mr. Gross was scheduled to present this research at the American Society for Pharmacology and Experimental Therapeutics annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team’s abstract was published in this month’s issue of The FASEB Journal.
Mr. Gross and colleagues examined human and canine glioblastoma cells because the cancer shows striking similarities between the two species. They tested the effects of CBD isolate, which contains 100 percent CBD, and CBD extract, which contains small amounts of other natural occurring compounds such as cannabigerol and tetrahydrocannabinol, or THC.
“Our experiments showed that CBD slows cancer cell growth and is toxic to both canine and human glioblastoma cell lines,” said Mr. Gross. “Importantly, the differences in anti-cancer affects between CBD isolate and extract appear to be negligible.”
The new work revealed that the toxic effects of CBD are mediated through the cell’s natural pathway for apoptosis, a form of programmed cell death. The researchers also observed that CBD-induced cell death was characterized by large, swollen intracellular vesicles before the membrane begins to bulge and breakdown. This was true for all the cell lines studied.
The researchers believe that CBD’s anti-cancer actions target mitochondria—the cell’s energy producing structures—by causing the mitochondria to dysfunction and release harmful reactive oxygen species. Their experiments showed that cells treated with CBD exhibited significant decreases in mitochondrial activity.
“CBD has been zealously studied in cells for its anticancer properties over the last decade,” said Mr. Gross. “Our study helps complete the in vitro puzzle, allowing us to move forward in studying CBD’s effects on glioblastoma in a clinical setting using live animal models. This could lead to new treatments that would help both people and dogs that have this very serious cancer.”
Next, the researchers plan to transition from cell cultures to animal models to test CBD’s effects on glioblastoma. If the animal studies go well, the work could progress to clinical trials on dogs that are being treated for naturally occurring glioblastoma at the Colorado State University Veterinary Teaching Hospital.
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Ratio matters: CBD and THC ratio plays key role improving quality of life in brain cancer patients – BioCeuticals-funded trial
The ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) in medicinal cannabis has shown to play a crucial role in improving the physical and functional wellbeing of brain cancer patients, according to newly published findings in a trial funded by BioCeuticals, the practitioner-only arm of Blackmores.
The 12-week double-blind RCT was conducted on 88 patients suffering from high-grade glioma – an aggressive brain cancer with a survival rate of six to 18 months.
Results from MRI scan of 53 participants also showed that 11 per cent of them reported a reduction in disease, 34 per cent were in stable conditions, 16 per cent had slight enhancement, and 10 per cent reported worsening of their condition.
Writing in Frontiers in Oncology, the researchers highlighted that a CBD to THC ratio of 1:1 led to more improvements in physical, functional capacities, as well as better sleep quality in these patients, as compared to the use of CBD to THC at the ratio of 1:4.
On the other hand, there was no difference between the two groups in terms of MRI tumour burden/control.
In other words, both ratios exerted similar effects when it comes to affecting the tumour size.
This is also said to be the first study that looked that medicinal cannabis use beyond pain relief and reduction of symptoms.
“Most of the other studies that are done in cancer for medicinal cannabis is actually for symptomatology, which means they are looking at how medicinal cannabis eases pain, nausea and vomiting.
“For this particular study, it was actually trying to look at the quality of life and the patients’ physical functionality, their ability to do everyday things such as walking, the moving of arms and legs, and being able to speak in a sentence.
“It also looked at how medicinal cannabis could enhance the current treatment that these particular patients are undergoing,” lead researcher Dr Janet Schloss told NutraIngredients-Asia.
World-first trial tests cannabis-based drug on aggressive brain tumours
A major UK trial of cannabis-based drug Sativex in treating the most aggressive form of brain tumour is to launch at 15 NHS hospitals, following promising results from a phase I study in 27 patients.
The new phase II trial, led by the University of Leeds, will assess whether adding Sativex – an oral spray containing cannabinoids THC and CBD – to chemotherapy, could extend life for thousands diagnosed with a recurrent glioblastoma. Currently, it has an average survival of less than 10 months.
The drug, already used in treating multiple sclerosis, was found to be tolerable in combination with chemotherapy, with the potential to extend survival, in a phase I trial in glioblastomas earlier this year.
While the phase I study observed that more patients were alive after one year in the Sativex arm compared to the placebo arm, the study was not sufficiently powered to show survival impact.
The new three-year phase II trial (ARISTOCRAT), funded by The Brain Tumour Charity and co-ordinated by the Cancer Research UK Clinical Trials Unit at the University of Birmingham, is due to begin recruiting more than 230 patients across all UK nations in early 2022, subject to sufficient funds being raised.
Having seen its income drop by more than 25% last year due to the pandemic and forced to pause its regular research grant funding programme, The Brain Tumour Charity has today launched an appeal to raise the £450,000 needed to open the trial as soon as possible.
Experts hope that, should the trial prove successful, Sativex could represent one of the first additions to NHS treatment for glioblastoma patients since temozolomide chemotherapy in 2007.
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.
“Glioblastoma brain tumours have been shown to have receptors to cannabinoids on their cell surfaces, and laboratory studies on glioblastoma cells have shown these drugs may slow tumour growth and work particularly well when used with temozolomide.
“Having recently shown that a specific cannabinoid combination given by oral spray could be safely added to temozolomide chemotherapy, we’re really excited to build on these findings to assess whether this drug could help glioblastoma patients live longer in a major randomised trial.”
Tackling aggressive brain cancer
Glioblastomas are the most common and most aggressive form of brain cancer, with around 2,200 people diagnosed each year in England alone. They are usually fast-growing and diffuse, with poorly-defined boundaries and thread-like tendrils that extend into other parts of the brain.
Almost all glioblastomas recur even after intensive treatment including surgery, radiotherapy and chemotherapy, and average survival is just 12-18 months from first diagnosis.
Over the last decade there has been significant global interest within both patient and scientific communities about the activity of cannabinoids in brain tumours, with the view that cannabinoid-based products may not only help relieve symptoms but could also have a positive impact on survival.
Several pre-clinical laboratory studies have suggested that cannabinoids THC and CBD may reduce brain tumour cell growth and could disrupt the blood supply to tumours – but to date, clinical evidence that they could treat brain tumours has been limited.
In this new phase II trial, researchers will assess whether adding Sativex to the current standard chemotherapy treatment (temozolomide) could offer extra time to live for adults diagnosed with a recurrence of their glioblastoma after initial treatment.
‘Life beyond a glioblastoma diagnosis’
Stephen Lee, 62 from Leyland in Lancashire, took part in the phase I trial of Sativex in 2015 after his glioblastoma returned following initial treatment. Stephen was first diagnosed in 2010, just a few months after he had very sadly lost his older brother to the same disease. Stephen said: “My diagnosis was very sudden and was one of those days you never forget. Having had to leave work early with a severe headache and a stabbing pain in my right eye, my wife insisted that we go straight to hospital after what my brother had experienced.
“I was admitted that same day, had a scan and that’s when they identified it was a brain tumour. I had the operation the following week, and beforehand my wife and I agreed that we wanted to stay positive, to keep living our lives and to enjoy however much time we had together.
Stephen Lee with his wife
“I joined the early trial of Sativex in the hope that it could improve my quality of life, but I also thought it was important to do so as the chemotherapy and radiotherapy I was having had all been trialled by other people before it could be used safely. I thought it only right and proper that I followed in their footsteps and joined a trial to help prove a new drug which could benefit so many people in the future with a recurring glioblastoma.
“I took the oral spray 10 times a day, and it was easy as I could take it wherever we were going, even while out for dinner. While I don’t know whether I had Sativex or the placebo, since the trial finished in 2016, all my MRI scans have been clear.
“This new trial is so important as it will give people hope that there could be life beyond a glioblastoma diagnosis and that there are other treatments being trialled to support them to live their lives.”
The ARISTOCRAT trial plans to recruit 232 participants across a minimum of 15 hospitals: two thirds of the participants will be given temozolomide plus Sativex, while one third will be given temozolomide plus placebo.
Sativex, manufactured by GW Pharma, is an oromucosal spray containing 1:1 THC (Delta-9-tetrahydrocannabinol) and CBD (cannabidiol), with the active ingredients being absorbed in the lining of the mouth, either under the tongue or inside the cheek.
Participants will be asked to administer up to 12 sprays per day (or to the maximum dose they can tolerate if fewer than 12) of Sativex or placebo oral sprays.
Participants will then undergo regular follow-up including clinical assessment (every four weeks), blood tests, MRI scans (every eight weeks), and they will complete quality of life questionnaires. This will also be one of the first trials to integrate with The Brain Tumour Charity’s app BRIAN.
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.
In the initial phase I study, the most common side-effects reported were fatigue, headache, vomiting and nausea, which were mostly classed as being mild-moderate in severity.
Dr David Jenkinson, Interim CEO at The Brain Tumour Charity, which is funding the trial, said: “We hope this trial could pave the way for a long-awaited new lifeline that could help offer glioblastoma patients precious extra months to live and make memories with their loved ones.
“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.
“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.
“But we also know that for many, this trial won’t come soon enough. In the meantime, while other cannabis-based products may help alleviate symptoms, there is insufficient evidence to recommend their use to help treat brain tumours. For anyone considering using cannabis-based products or other complementary therapies, it’s vital that you discuss these with your medical team first, as they could interact with other treatments such as anti-epileptic medicines or steroids.
“Anyone affected by a glioblastoma can speak to us for support and information on 0808 800 0004 or by emailing [email protected] If you need someone to talk to, we’re here for you.”