Medical cannabis for severe treatment resistant epilepsy in children : a case-series of 10 patients
Rayyan Zafar, Anne Schlag, Lawrence Phillips, David J Nutt
BMJ Paediatrics Open, 2021, 5, e001234.
doi : 10.1136/bmjpo-2021-001234
Objectives : To report the findings of a case-series of 10 children suffering with intractable epilepsies in the UK to determine the feasibility for using whole-plant cannabis medicines to treat seizures in children.
Setting : This study was conducted retrospectively through collecting clinical data from caretakers and
clinicians on study outcome variables. Participants were recruited through the MedCann Support and End our Pain charity groups which are patient representative groups that support children who are using medical cannabis to treat their epilepsies. Medicines were prescribed to patients by clinicians in both National Health Service and private medical practices. Follow-up calls were conducted throughout the period January 2021 to May 2021 to keep data recorded up to date.
Participants : Ten children, 18 years old or under, with intractable epilepsies were recruited from two charities. There were no limitations on diagnosis, sex or ethnic origin.
Interventions : Participants were treated with a range of whole-plant medical cannabis oils. Individual dosing regimens were determined by clinicians. Primary outcome measure The primary outcome
measure was seizure frequency.
Results : Seizure frequency across all 10 participants reduced by 86% with no significant adverse events. Participants reduced use of antiepileptic drugs from an average of seven to one following treatment with medical cannabis. We also noted significant financial costs of £874 per month to obtain these medicines through private prescriptions.
Conclusions : This study establishes the feasibility of whole-plant medical cannabis as an effective and
well-tolerated medicine for reducing seizure frequency in children suffering with intractable epilepsies. These findings justify the potential value of further research into the reported therapeutic benefit of whole-plant medicinal cannabis products.
Though used for millennia in eastern medicine, the advent of medical cannabis as a therapeutic tool to treat seizures in the west was first noted in 1843 by an Irish physician, Dr O’Shaughnessy. He observed that cannabis tinctures resolved seizures in a febrile infant, thus claiming that medicine had found an
anticonvulsant of the highest order.1 In 1971, both recreational and medical cannabis were made illegal in the UK under the Misuse of Drugs Act 1971 and so cannabis research largely ceased. Led by parents whose children had responded well to whole-plant medical cannabis extracts but who had failed on conventional antiepileptic drugs (AEDs) and purified cannabidiol (CBD) (Epidyolex), medical cannabis was re-initiated as a medicine in the British pharmacopeia in 2018.
Cannabis-based medical products (CBMPs) comprise a broad range of medicines. They can be plant based or synthetic and vary from purified single compounds (often THC or CBD) to complex mixtures of hundreds of molecules, in multiple formulations (oils, solutions, sublingual sprays, tablets and capsules), with multiple delivery mechanisms (oral, nasal, rectal and inhalation).2
Of the products licensed in the UK, Epidyolex (licensed for the treatment of epilepsy) is an isolate, Sativex (recommended for spasticity associated with multiple sclerosis) comprises a 1:1 CBD:THC isolate ratio, and nabilone (eg, used to treat nausea and vomiting due to cancer chemotherapy) is a THC analogue.
A combination of both THC and CBD from whole plant extracts were found to be superior to CBD alone in children suffering from various forms of epilepsy.3
Despite the change in legal status of medical cannabis, most of these children have not benefited as to date there has been only three National Health Service (NHS) CBMPs prescriptions made in total and only two in children.4 Many patients are thus forced to resort to private treatment which costs up to £2000 per month.3
Reasons for this resistance are multifactorial.5 6 One of the most argued by clinicians who might be prescribers is the lack of evidence for efficacy of medical cannabis. By this they usually mean that there are no randomised controlled trials (RCTs) that prove efficacy and without these they are not prepared to prescribe. To a lesser extent this has also limited National Institute for Clinical and Healthcare Excellence (NICE) support.7 It is generally accepted that RCTs though powerful are not the only
means to generate evidence for the value of treatments.
The previous head of NICE and the Medicines Healthcare Regulatory Agency (MHRA) Sir Michael Rawlins in his 2008 Royal College of Physicians Harveian lecture argued that there are many other ways of collecting useful clinical evidence highlighting :
‘Randomised controlled trials, long regarded at the ‘gold standard’ of evidence, have been put on an
undeserved pedestal. Their appearance at the top of ‘hierarchies’ of evidence is inappropriate; and hierarchies, themselves, are illusory tools for assessing evidence. They should be replaced by a diversity of approaches that involve analysing the totality of the evidence-base’.8
In a recent position statement, NICE declared their willingness to acknowledge additional data sources
including ‘real world’ data and ‘relevant data collected outside of the context of traditional trials’.9 One of these other sources of data, real-world evidence, comes from patient case-series with before and after outcome measures. These are particularly useful for conditions where RCTs are unlikely or impossible to perform in examples of rare and idiopathic conditions and especially in paediatric medicine. For this reason, we have conducted an outcome assessment of the use of medical cannabis in 10 children with severe treatment-resistant epilepsy who have all failed on multiple traditional AEDs and many of whom have failed on the licensed CBD preparation Epidyolex. Epidyolex is a licensed, pharmaceutical grade, purified CBD medicinal product that is produced by GW Pharma. It is the first and only approved prescription CBD. It is approved to treat seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome or tuberous sclerosis complex (TSC) in patients 1 year of age and over.
Our previous study, an open label retrospective study of the impact of medical cannabis in 10 patients found whole plant extracts to be superior to CBD isolate and a mean 80% reduction in seizure frequency in a range of intractable childhood epilepsies where standard treatment had failed.3 A subsequent qualitative follow-up study highlighted the various benefits patients and their families experienced as a result of treatment with CBMPs.