Epileptic seizure frequency fell by 86% in kids treated with whole plant medicinal cannabis
None of the children had responded to other treatments, including the only cannabidiol (CBD) product licensed for their condition.
The findings prompt the researchers to call for further exploration of the potential therapeutic benefits of whole plant medicinal cannabis products.
Substantial anecdotal evidence on the value of medicinal cannabis for treating childhood epilepsies has been accumulating since the 1800s, say the researchers. But there’s not been much recent scientific evidence on the effectiveness of whole plant cannabis extracts.
Whole plant cannabis includes tetrahydocannabinol or THC for short, the main active ingredient of the plant that is responsible for the characteristic ‘high’ associated with recreational use, plus cannabidiol, other neuroactive cannabinoids, and molecules such as terpenes.
Both recreational and medical cannabis were made illegal in the UK under the Misuse of Drugs Act 1971 so cannabis research largely ceased, point out the researchers.
But prompted by parents whose children had responded well to whole plant medicinal cannabis extracts, but not to conventional antiepileptic drugs or purified cannabidiol (CBD oil), medicinal (whole plant) cannabis was designated a prescription medicine for the treatment of severe childhood epilepsy in 2018.
But doctors in the UK have been extremely reluctant to prescribe this to children with severe epilepsy, largely because of the lack of confirmatory clinical trial data.
The UK’s National Institute for Health and Clinical Excellence (NICE), which provides guidance on which treatments and therapies the health service in England should adopt, has accepted that real world data, including case series, are valid sources of evidence, particularly where it’s difficult to carry out clinical trials–in children, for example.
In light of this, the researchers evaluated the use of whole plant medicinal cannabis in 10 children whose severe epilepsy hadn’t responded to conventional treatment, and two of whom hadn’t responded to the only pharmaceutical grade, purified CBD oil licensed for the condition in children (Epidyolex).
The researchers wanted to assess the percentage change in monthly seizure frequency and the impact of medicinal cannabis on changes in conventional epilepsy drug use. They also wanted to report the strengths and doses used and the costs incurred.
All the participants were recruited from two charities representing children using medicinal cannabis to treat their severe epilepsy. The children’s average age was 6, but ranged from 1 to 13 years. They had a range of epilepsies and three had other concurrent issues, including infantile spasms, learning disabilities, and global developmental delay.
Data were collected from their parents or carers via phone or video conference calls between January and May 2021.
The children had tried an average of 7 conventional epilepsy drugs. After starting to take medicinal cannabis, this fell to an average of 1 each, with 7 of the children stopping them completely.
Monthly seizure frequency reduced for all 10 children by an overall average of 86%.
Full chemical analysis of the whole plant medicinal cannabis products used is ongoing, but the researchers were able to assess the THC and CBD content. This showed that the children took an average of 5.15 mg THC and 171.8 mg CBD every day.
The average monthly cost of the medicinal cannabis products was £874. One child had obtained their prescription for free on the NHS.
Parents and carers reported significant improvements in the health and wellbeing of their children, including in sleep, eating, behaviour and cognition after they started to take whole plant medicinal cannabis products. Only a few minor side effects, such as tiredness, were reported.
This is an observational study involving a small number of participants. And the researchers acknowledge that it was retrospective and relied on parental recall, with no comparator group. And it’s possible that only those parents in whom medicinal cannabis worked well decided to take part.
But the researchers highlight that their findings are in line with several observational and controlled interventional studies showing significant reductions in seizure frequency after treatment with medicinal cannabis.
What’s more, the new data suggest that whole plant medicinal cannabis products are more effective than CBD products.
“Further research is required to elucidate the mechanisms by which the respective additive constituents of whole-plant products lead to superior clinical results,” write the researchers.
And this must include comparing the unwanted effects of whole plant medicinal cannabis with the known harmful effects of conventional epilepsy medicines, they say.
But they conclude: “We believe that our data on whole-plant medical cannabis in childhood-onset severe treatment-resistant epilepsy, provides evidence to support its introduction into the NHS within current NICE prescribing guidelines.
“Such a move would be hugely beneficial to the families, who in addition to having the psychological distress of looking after their chronically ill children, have also to cover the crippling financial burden of their medication.”
Notes for editors
Research: Medical cannabis for severe treatment resistant epilepsy in children: a case series of 10 patients doi:10.1136/bmjpo-2021-001234
Journal: BMJ Paediatrics Open
Funding: None declared
Link to AMS press release labelling system: https://press.psprings.co.uk/ AMSlabels.pdf
Externally peer reviewed? Yes
Evidence type: Observational
The use of cannabis to treat epilepsy and other neurological conditions has been studied for a number of years. It has been hotly debated too.
On June 25, 2018, the U.S. Food & Drug Administration (FDA) approved EPIDIOLEX ® (cannabidiol, CBD) oral solution for the treatment of seizures associated with two epilepsy syndromes – Lennox-Gastaut syndrome and Dravet syndrome – in people two years of age or older. Epidiolex represents a new medication option for children with these types of epilepsy. It is also the first ever FDA approved medication to treat seizures in Dravet syndrome.
What does FDA approval of Epidiolex (CBD oral solution) mean?
The FDA approval and Drug Enforcement Administration (DEA) scheduling of Epidiolex brings to market the first plant-based drug derived from the cannabis plant in the U.S.
What is medical cannabis?
Cannabis is known by many names – the most common is marijuana. Cannabis is the Latin name used most often by botanists and pharmaceutical companies. The word marijuana usually refers to the leaves and female flowers of the cannabis plant. Medical cannabis is whole plant marijuana or chemicals in the plant used for medical purposes.
Cannabinoids are substances in cannabis that act on cells in the body (called cannabinoid receptors) to cause some effect. Two major ingredients include
- Tetrahydrocannabinol, or THC, which causes the psychoactive effects of “getting high”
- Cannabidiol, or CBD, which does not cause psychoactive effects but has shown some positive effects on certain body systems. This is the part that has been effective in reducing seizures in some people with epilepsy.
Does cannabis help seizures?
Early evidence from laboratory studies, anecdotal reports, and small clinical studies over a number of years suggest that cannabidiol (CBD) could potentially help control seizures. Research on CBD has been hard to do and taken time due to federal regulations and limited access to cannabidiol. There are also many financial and time constraints. In recent years, a number of studies have shown the benefit of specific plant-based CBD product in treating specific groups of people with epilepsy who have not responded to traditional therapies.
What do I need to know about hemp?
Hemp is a variety of Cannabis Sativa L. plant historically grown for fibrous materials found in its stalks and seeds. It has been used to make items such as clothing fiber, upholstery, and other household items.
Hemp traditionally contains lower concentrations of THC and higher levels of CBD. Cannabinoids extracted from hemp plants, including CBD, have until recently been classified as marijuana and considered Schedule I substances. Per the DEA, Schedule I substances currently have no accepted medical use and have a high potential for abuse. A federal law* enacted in December 2018, however, reclassifies hemp and hemp-derived CBD as an agricultural commodity and exempts it from the list of Schedule I Drugs.
Despite this change in the classification of hemp and hemp-derived CBD, the only CBD product that has been rigorously studied and approved to be used as a medical therapy for epilepsy is the drug Epidiolex. While more CBD products may come to market in the coming months, it is important to understand that not every CBD product is the same quality or uniform from batch to batch. Any drug or supplement that is being considered for use as a medical treatment should first be discussed with your doctor. The potential for benefit as well as the interaction with other seizure medications and possible side effects require careful review with your doctor.
*The Agriculture and Nutrition Act of 2018 (H.R. 2) legalizes hemp and hemp-derived CBD. The bill changes the definition of hemp to encompass any plant or product derived from the plant that contain less than 0.3% THC by dry weight and classifies them as exempt from the controlled substance restrictions applied to marijuana. The law further amends the Controlled Substances Act to exempt hemp from Schedule I drugs.
What do I need to know about hemp?
Epidiolex (Cannabidiol, CBD)
Studies in the U.S. of Epidiolex (a plant-based CBD formulation) have been ongoing for a number of years. Data from these studies has helped provide evidence that led to the FDA approval of this product on June 25, 2018.
Epidiolex is a purified (> 98% oil-based) CBD extract from the cannabis plant. It is produced by Greenwich Biosciences (the U.S. based company of GW Pharmaceuticals) to give known and consistent amounts in each dose.
Researchers studied this medicine in controlled clinical trials. These studies used a control group with some people taking a placebo while others were given CBD at different doses. Researchers did not know who was getting the placebo and who was getting CBD. These tpyes of studies are called “gold standard” studies.
A summary of the Epidiolex clinical trials is found below:
- In controlled and uncontrolled trials in people with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, 689 people were treated with Epidiolex (CBD), including 533 people treated for more than 6 months and 391 people treated for more than 1 year.
- In an expanded access program and other compassionate use programs, 161 people with Dravet syndrome and LGS were treated with Epidiolex, including 109 people treated for more than 6 months.
- All study participants were taking other seizure medications.
- In controlled trials, the rate of stopping the medicine due to any side effect was small and happened most in people taking the higher dose of Epidiolex.
- The most frequent cause of stopping treatment with Epidiolex was a change in liver function.
- Sleepiness, sedation, and lethargy led to stopping Epidiolex in 3% of people taking the higher dose.
- The most common side effects were sleepiness, decreased appetite, diarrhea, change in liver function, fatigue, malaise, asthenia (weakness or lack of energy), rash, insomnia, sleep disorder, poor quality sleep, and infections.
Results from Gold Standard Studies of Epidiolex (CBD)
NEJM May 2018
Summarized below are the results from a study published in the New England Journal of Medicine in May 2018.