Today, 26 March, marks Purple Day; an international grassroots effort dedicated to increasing awareness about epilepsy across the globe. This year, we’re taking the opportunity to delve into what can be seen as a controversial area – the use of cannabis-derived therapeutics for the treatment of epilepsy. Historically, the use of such agents has been reported to improve symptoms in a number of neurological disorders, but research into the mechanisms behind this and the risks involved remains limited. However, in the past year alone, we’ve seen positive results in a number of studies investigating the use of cannabidiol, for example in the reduction of seizures in patients suffering from Lennox-Gastaut syndrome, suggesting these products could soon become more commonplace in the therapeutic landscape.
To find out more about the current status of the use of cannabis-derived therapeutics in the treatment of epilepsy, we spoke to Hannah Cock, Clinical Advisor for Epilepsy Action (UK), Professor of Epilepsy & Medical Education and Consultant Neurologist (St George’s, London, UK).
Could you give us a brief overview of the current consensus on the use of cannabinoids in the treatment of epilepsy?
The use of cannabinoids in the treatment of epilepsy is far from simple. Research suggests that there is promise, but there are also risks and unknowns about it.
There are a few parts of the cannabis plant that may have potential for treating epilepsy. These include cannabidiol (CBD) and tetrahydrocannabinolic acid (THCA). There are very few studies on THCA, but there are suggestions that this may have some medical properties in reducing muscle spasms. However, this part of the cannabis plant has a link with the part that gives the experience of a ‘high’ – tetrahydrocannabinol (THC). This means that as well as there being little evidence on how effective it is, it is also currently illegal in many countries. In the UK, THC and THCA are illegal under the Misuse of Drugs Act 1971.
CBD is, however, the part of the cannabis plant that holds a lot of promise as a possible new treatment for epilepsy. CBD is believed to have anti-epileptic effects and does not cause a ‘high’. At the moment, it is the subject of a lot of research, but as yet there is no CBD medicine currently available for routine prescription in the UK.
In October 2016, the government’s Medicines and Healthcare products Regulatory Agency (MHRA) put out a statement about products containing CBD. They stated that such products used for medical reasons are a medicine.
In the UK however, any medicine must have a licence before it can be legally sold, supplied or advertized, and at the moment there is no CBD medicine that is licensed for epilepsy in the UK.
In very rare, exceptional cases, doctors can make an individual decision to recommend an off-licence product. An off-licence product could be a potential new medicine that has not received a licence yet. It could also be a medicine that is licensed for use for a different condition, but may have helpful effects for another condition. There are also ongoing clinical trials for which some patients may be eligible.
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What data on the efficacy and safety of the use of cannabinoids have been presented so far? What are the main benefits and risks associated with this form of therapy?
At the moment, CBD is being trialled only for rare types of epilepsy, like Dravet syndrome and Lennox-Gastaut syndrome (LGS), and seizures associated with tuberous sclerosis complex.
It is not completely known how safe and effective it is yet. Most of the available evidence about effectiveness is in children with rare and hard-to-treat epilepsies. There are data published on approximately 200/300 children with these conditions, though that is still quite a small number.
The number of children, however, who are seizure free on CBD – especially as these are some of the most severe and difficult to-treat epilepsies – looks promising: it’s up to one in ten. That still means nine in ten are not seizure-free, but given the nature of these conditions, that is higher than we see from other medicines. And there is also another big group who have a meaningful reduction in seizures – something like a 70% reduction in seizures. Or they sometimes have freedom from convulsive seizures – in up to one-third of children. These are meaningful results in terms of effectiveness, so it looks very promising.
But it is also quite short-term at the moment. They are mostly studies of 6–18 months, and we know that epilepsy is variable in nature. We need to look at longer-term data before we can really be confident about the effectiveness.
In conditions like epilepsy, there are good spells and bad spells. So it can be hard to know if early reported improvements in individual patients have just happened naturally or truly because of the medicine. This is why bigger trials and longer-term data are important.
The safety data have so far also been promising, although they have shown that there are some side-effects. These include diarrhoea, drowsiness and fatigue, but again, long-term studies are needed.
The long-term safety of this possible new medicine is just not yet known. There are many historical examples of drugs that looked safe in early studies but it later became clear later that they weren’t.
CBD has been mainly studied on children with severe epilepsies because they are the group that needed something new. More trials in time will tell if this medicine could have an effect on other epilepsies too, as currently there is no good data from anywhere on other epilepsies. There is also no evidence or reason to think that for most epilepsies CBD would be better than other medicines. The studies in this group so far have just shown that it would be better than taking nothing.
In the studies on hard-to-treat epilepsies in children, it has always been given as an add-on to their other medicines. There are very little data on how CBD interacts with these other medicines. There are also still worries about cannabis causing mental health problems, particularly in children and adolescents. It is believed that this is due to the THC part of the cannabis plant, not CBD, but all of that needs to be tested.
This branch of research can be seen as controversial and can be more scrutinized than other areas of medical research – what challenges do such factors pose for the advancement of knowledge?
From a regulatory perspective, cannabinoids are not scrutinized more than other areas of medical research. They are subject to the same regulatory processes and clinical trials as all other medicines.
There is greater scrutiny from the public and media on this area, primarily because of cannabis’ status as a recreational illegal drug. However, the media often fails to acknowledge or explain the difference between CBD and cannabis.
Some researchers are concerned that the research on cannabis will continue to focus on the social harms associated with recreational use rather than the potential therapeutic benefits of medical cannabis.
There is a perception that the progress of research into CBD has been slow. However, the clinical trials that form part of the regulatory process can take years to complete. The public perception that progress has been slow may be due to the fact that cannabis has been available illegally for many decades, while medicinal research has begun relatively recently.
What is the future outlook? Are therapeutic cannabinoids a feasible route for the future of epilepsy treatment? How will their use be regulated?
Researchers are still working hard to ensure that CBD is safe and effective for children with hard-to-treat epilepsies. All the trials are pushing us towards this medicine being licensed by the MHRA.
GW Pharmaceuticals (Cambridge, UK) has developed a CBD product, Epidiolex, which has undergone trials in children with Dravet syndrome and Lennox-Gastaut syndrome and has been shown to reduce convulsive seizures.
GW Pharmaceuticals have put their CBD product forward for consideration with the US FDA and the EMA to be approved as a licenced medicine. It is possible that a licence for this medicine is on the horizon, with a decision from both expected sometime this year.
It will likely then also be followed by research in other patient groups with more common epilepsies. At least one study on CBD is also about to open in the UK for children and adults with tuberous sclerosis complex, and others will likely follow.
Momentum is already building. In March 2017, Oxford University (UK) announced a new £10 million research program into medical cannabis. In June 2017, cannabinoid biotechnology company, MediPen, announced the launch of a dedicated research facility. This will also provide a platform for anyone looking to utilize its facilities for the purposes of driving innovation around the use of medicinal cannabis.
It seems likely that there will be a licence in the not-too distant future for children with severe, difficult-to treat epilepsies. In the UK, NICE will then consider who it should be available to and how it will be funded, based on the evidence.