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.”
There’s now conclusive evidence for the use of cannabis-based products for managing the side-effects of a brain tumour.
Cannabis, cannabinoids and cannabis derivatives
Cannabis is the dried preparation, or resinous extract, of the flowers or leaves of the cannabis plant, a member of the hemp family.
The parts of cannabis that are considered important for medical reasons are called cannabinoids. This is the name for the complex chemicals found in cannabis that are responsible for the effect cannabis has on the body. Two cannabinoids are of particular interest:
- THC – delta-9 tetrahydrocannabinol (responsible for the psycho-active and addictive effects of cannabis)
- CBD – cannabidiol
Cannabis derivatives is a general term for all products that are produced using different parts of the cannabis plant, including:
- cannabis-based medicines that certain healthcare professionals can prescribe (for example, Sativex and Nabilone)
- cannabis products that don’t contain THC, which can be sold legally in the UK as food supplements (for example CBD oil or hemp oil)
- cannabis products that do contain THC, which are currently illegal in the UK (for example, street cannabis or cannabis oil).
It’s important that you understand the difference between cannabis products that contain CBD and cannabis products that don’t contain THC, as they can have different effects and are legally treated differently.
Our community share their experiences with cannabis-based products
“I am having chemotherapy and using CBD oil to help with the side-effects of that.”
“I used CBD oil to relax and try to reduce my anxiety levels.”
“I hoped CBD oil would reduce the size of my tumour, however it did grow. I use CBD oil to help with pain, and it makes me calmer and more relaxed.”
“I have never used cannabis products because my doctor wasn’t sure how it would interact with my other medications.”
“I did not use cannabis medicines or products because I didn’t think they would improve or enhance the medication I was receiving.”
“I believe it can help with nausea, but talk to your doctor first because cannabis can interact with other medications.”
These experiences from members of the brain tumour community are not intended as medical advice. Everyone is different and we encourage you to make decisions about using cannabis-products following discussion with your medical team.
Join the conversation in our Online Support Communities for more tips about coping with a brain tumour diagnosis from people who truly understand what you’re going through.
Are cannabis-based products legal in the UK?
Cannabis is an illegal drug in many countries, including the UK, where it is classified as a class B drug. This means it is illegal to posses, supply or produce cannabis in the UK.
Cannabis-based products containing THC (for example, cannabis oil or medical cannabis) are also illegal in the UK, unless you have a valid prescription.
Possession of a class B drug is punishable in the UK with up to 5 years in prison, an unlimited fine or both. Supply and production of a class B drug is punishable with up to 14 years in prison, an unlimited fine or both.
CBD and hemp oils
Cannabis-based products that don’t contain THC (for example, hemp oil or CBD oil) are currently legal in the UK – as long as it has been produced from an EU-approved strain of hemp and as long as it is marketed as a food supplement without any medicinal claims. You can buy these products in many high street health food shops.
Buying cannabis-based products that aren’t from an EU-approved strain of hemp often means you cannot be sure the product is legal in the UK.
What is the evidence for cannabis-based products in the treatment of brain tumours?
Treating brain tumours
Currently, the evidence that cannabis-based products can treat brain tumours themselves is limited.
Preliminary studies from the lab suggest that cannabinoid chemicals THC and CBD can stop glioblastoma (GBM) cells from growing, causing them to die and disrupting the blood supply to the tumour cells.
And, earlier this year, an early-stage trial led by Professor Susan Short suggested that adding a specific blend of these chemicals – in the form of a drug called Sativex – to chemotherapy could potentially help treat recurrent GBMs more effectively.
There’s now conclusive evidence for the use of cannabis and its products, such as cannabis oil and CBD oil, for other therapeutic purposes, i.e. pain relief and treating chemotherapy-induced nausea and vomiting.
As such, the cannabis-based drug, Nabilone, has a medical licence and can be legally prescribed for chemotherapy-induced nausea and vomiting.
Cannabis medicines have been used to help with nausea, however these are different to the products that have been tested for use to treat cancers.
Professor Susan Short, Consultant in Clinical Oncology
If you have a question you can’t find an answer to on this page, please contact our Support and Information Line by ringing 0808 800 0004, emailing us at [email protected] or starting a live chat. The Support and Information Line is open Monday to Friday, between 9.00am and 5.00pm.
Is it safe to use cannabis-based products?
Any supplements, alternative or complementary treatments that you or your loved one wish to use could interact with other medications, such as anti-epileptic medicines, steroids or chemotherapy. You should always discuss this with your medical team before deciding to use cannabis-based products.
It is important to be aware that you cannot be sure of the concentrations and ratios of THC and CBD in grown or street cannabis, and therefore cannot guarantee how safe it is. The same is true of other cannabis-products that aren’t prescribed by your healthcare team or produced from an EU-approved strain of hemp.
How safe a cannabis product is will depend on the product itself and the other medications you are taking. You should speak to your medical team for advice before starting cannabis products.
Professor Susan Short, Consultant in Clinical Oncology
Side effects of using cannabis-based medications
Like all medications, cannabis-based medicines have side-effects. These will differ depending on the product you’re using, as well as your individual circumstances.
Your consultant or medical team will be able to talk to you about possible side-effects as well as how to manage any side-effects you’re experiencing.
The side-effects may vary depending on the product. The common side-effects of Sativex (a cannabis-based medicine) are sickness, tiredness, dizziness and headaches.
Professor Susan Short, Consultant in Clinical Oncology
How can I get cannabis-based products?
Only specialist doctors who are listed in the General Medical Council’s (GMC) specialist register will be able to prescribe cannabis-based products. They will only be prescribed when the specialist considers that the patient will benefit and when the patient has an unmet special clinical need that cannot be met by licensed products.
- Medicinal cannabis, therefore, will be prescribed on a case-by-case basis
- Patients will NOT be able to get cannabis-based products from their GP
- If you feel you might benefit from these products, speak to your consultant or healthcare team
- Administration by smoking remains prohibited.
If you’d like to know more, you could read our blog post on cannabis-based medicinal products or read our information about accessing unlicensed drugs.
CBD and hemp oils
CBD and hemp oils do not contain THC and can be purchased in many high street health food shops.
Cannabis-based medicines are only available through a medical prescription. Cannabis-based products are available without a prescription but many of these are of unknown composition and are not equivalent to medicinal products.
Professor Susan Short, Consultant in Clinical Oncology
Speaking to your medical team about cannabis
We recognise this can be a difficult conversation to start with your, or your loved one’s, medical team. If you are interested in understanding if cannabis-based medications may be suitable for you or your loved one, or if you are considering a non-prescription cannabis product like CBD oil, we recommend you speak with your medical team about this decision.
Cannabis-based medications (medical cannabis) are only likely to be prescribed to a small number of people, and only for specific reasons
Here are some tips to help you have this conversation:
- Explain why you are interested in cannabis-based medicines or products, and what you are hoping it could do for you or your loved one.
- Let your medical team know you want them to be involved in decisions about using cannabis-based medicines or products.
- Ask about research or clinical evidence for or against using cannabis-based medicines or products, and how this relates to your individual circumstances.
Remember, a medical professional’s concern is your health or the health of your loved one. This means they are likely to be open to discussing any medicines or complementary therapies that may be suitable.
Perhaps your medical team will say they don’t recommend any cannabis-based medicines or products for you. You can ask them why. There are often clinical and evidence-based reasons why cannabis-based medicines and products would not be suitable for you or your loved one. For example, because of interactions with other medications.
You may find the UK Medical Cannabis Clinicians Society’s (UKMCCS) guide to medical cannabis helpful when talking to your medical team. It includes information about access, legality, safety and side-effects of medical cannabis.
If you have further questions, need to clarify any of the information on this page, or want to find out more about research and clinical trials, please contact our team: