Dr Ram Kumar at a recent meeting of the Rett Disorders Working Group
Following the heart-breaking case of Billy Caldwell, there has been widespread media coverage of cannabinoid medicines and their potential to treat epilepsy.
None of this was news to the families of Rett patients, who know all too well the pain and powerlessness they feel witnessing their daughter’s seizures.
Now, the UK Government has agreed to legalise cannabis-based medicines for prescription on the NHS in some limited circumstances.
But how effective are cannabinoids? What chances are there of our daughters receiving these treatments? Is this all more hype then help?
We spoke to leading paediatric neurologist, Dr Ram Kumar, a consultant at Alder Hey Children’s NHS Foundation Trust to understand the state of the medical evidence, and the implications of the government’s action.
Rachael: Ram, thanks for talking to us. Firstly – please could you explain your understanding of the government’s recent legislation: what action have they taken?
Dr Ram Kumar: From 1 November 2018, the home secretary and Chief Medical Officer will be allowing “medicinal cannabis” preparations to be prescribed by General Medical Council registered medical practitioners – essentially doctors including NHS or private practice. Because these products do not have full licensing yet, it is still a quite complex situation and access will remain quite strictly controlled.
Most likely the prescriber will need to be a paediatric neurologist, adult neurologist or someone equivalently experienced. The indemnifying body (employer) of the doctor who agrees to prescribe would also need to go through its own processes before allowing the medicinal cannabis to be prescribed. So it may be the case that these products are not available immediately after the legislation kicks in.
Rachael: Thanks; so what is the medical / legal difference between the medicines that they have legalised and simple street cannabis?
Ram Kumar: It is slightly tricky as ‘medical cannabis’ or ‘medicinal cannabis’ are not well-defined, and remain very loose terms. Regular street cannabis contains a mixture of individual chemicals. For our purpose, the most important two are ‘CBD’ (cannabidiol), which is an active ingredient that does not cause a high, and THC which is psychoactive – it causes a high.
Because of this, any medically unlicensed preparation which contained more than 0.2% THC was previously illegal, as it was not considered to be of any medical benefit. My understanding is that this changes from 1 November 2018.
Billy Caldwell’s case involved him taking a preparation with more than 0.2% THC. The specific licensed medication called “Sativex” is 50% CBD and 50% THC. This was already legal for treatment of spasticity, most frequently in MS patients, but not epilepsy. By contrast, the CBD oil manufacturer says it is mostly CBD but it’s not completely clear how reliable that claim is.
Rachael: Okay, but are those the best potential medicines for Rett syndrome? As our readers may know, in April this year another cannabinoid, Epidiolex, was approved by the USA Food and Drug Administration for treatment of seizures in LG and Dravet Syndrome.
When will it be approved by the European Medicines Agency and how long do you think it will take for NICE (the NHS drug licensing body) to subsequently review/how long until it becomes available for use in the UK?
Ram Kumar: Epidiolex will likely be approved within the next few months. The company is starting to provide wider use for Dravet and LGS based on application to a special national panel which appears to be in preparation for licencing by EMA.
In general, most epilepsy medications are used more widely than the official licence since most severe epilepsies in children do not come under any one diagnosis.
Rachael: Are there any specific indications that Epidiolex will be effective for Rett Syndrome?
Ram Kumar: Well, as I said it is likely to be prescribed for the epilepsy symptoms associated with a number of underlying conditions. However, GW Pharma, the company that make Epidiolex, is planning a trial in Rett syndrome although not targeted specifically at epilepsy. So we should be cautiously optimistic.
Rachael: What’s the difference between Sativex and Epidiolex and is Sativex available for use off label?
Ram Kumar: Sativex is 50:50 THC:CBD whereas Epidiolex is close to 100% CBD. THC has both pro and anti convulsant properties, so Sativex has these pro and anticonvulsant properties. Sativex is a treatment for spasticity, which is where muscles become permanently contracted. It is only licenced for multiple sclerosis spasticity.
I have previously recruited 12 patients to an international trial of Sativex for spasticity, some of whom had epilepsy. One child had resolution of seizures for the first time since I knew them for many years. Another developed seizures for the first time after Sativex and whenever the dose was altered.
The numbers were too low to say what the effect of Sativex was, but I take it from this experience that Sativex is not a treatment reliably for epilepsy.
Rachael: Is there anything else you think families should know?
Ram Kumar: Yes - watch this space regarding Epidiolex trial in Rett syndrome. It is mentioned on the GW Pharma website. I know Reverse Rett will be sharing more news in the next few months. You can also read the full position of our professional body, the British Paediatric Neurology Association, here.