Further therapeutic benefits of whole plant products now worth exploring, say researchers Epileptic seizure frequency fell by an average of 86% among 10 children treated with whole plant medicinal cannabis, reveals a case series, published in the open access journal BMJ Paediatrics Open. None of the children had responded to other treatments, including the only cannabidiol […] Epidiolex, a cannabidiol (CBD) drug that treats seizures in children with Dravet syndrome and Lennox-Gastaut syndrome, may help reduce symptoms in a broader range of doses.
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
CBD Medication Reduces Seizures in Children on Multiple Anti-Epileptic Drugs, Researchers Find
New study supports possible lower dosing levels of FDA-approved drug derived from cannabis for difficult-to-treat type of epilepsy.
Everyday Health Archive
The cannabidiol (CBD) drug Epidiolex — already approved by the U.S. Food and Drug Administration (FDA) to treat seizures in children caused by Dravet syndrome and Lennox-Gastaut syndrome — may now help reduce symptoms in a broader range of doses.
New research published March 2, 2020, in the journal JAMA Neurology confirmed prior study outcomes demonstrating the effectiveness of this oral medication for Dravet syndrome at a dose of 20 milligrams per kilogram (mg/kg) per day. (The drug, which comes in a sesame oil with strawberry flavoring, is given according to a child’s weight.)
Results Show That a Lower Dose Is Safe, Effective
“This is the first study, however, to show efficacy and safety for a 10 mg/kg a day dose in these patients,” says lead investigator Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami. “It will not change the FDA indication, but will inform physicians regarding optimizing the benefit-risk ratio for patients.”
The trial, which included 199 patients ages 2 to 18 with a confirmed diagnosis of Dravet syndrome, showed that the 10-mg dose may be just as effective as the 20-mg dose.
Scientists discovered that those taking 10 mg experienced seizure reductions of 49 percent compared with 46 percent reduction in those taking 20 mg and a 27 percent reduction for those on placebo.
Stephen Schultz, the vice president of investor relations for GW Pharmaceuticals, which makes Epidiolex, indicates that the results should give physicians greater flexibility when it comes to dosing. “For some patients, the 10 [mg] will work well, but others will be more resistant and will need more,” he says.
Notoriously Resistant to Treatment
Dravet syndrome is a rare, catastrophic form of lifelong epilepsy that affects about 1 in every 15,700 individuals in the United States, according to the Dravet Syndrome Foundation.
This severe epilepsy can bring on frequent, prolonged seizures often triggered by high body temperature (hyperthermia), as well as developmental delay, speech impairment, ataxia (a degenerative disease of the nervous system), hypotonia (decreased muscle tone), sleep disturbances, and other health problems.
So far, the condition has been extremely challenging to treat, with response to medication being inadequate. The participants in this investigation were taking multiple anticonvulsants, such as levetiracetam, divalproex, topiramate, zonisamide, ethosuximide, and clobazam.
“Even with these currently available treatments, only about 10 percent of patients with Dravet syndrome achieve adequate seizure control,” says Dr. Miller.
A report published in September 2019 the journal CNS Drugs, however, highlighted new therapies — including stiripentol, fenfluramine, and cannabidiol — which have produced promising results in reducing convulsive seizure frequency.
Greenlighted by the FDA for Dravet syndrome treatment in June of 2018, Epidiolex is the first prescription pharmaceutical formulation of a highly purified, plant-derived cannabinoid — but without the “high” associated with marijuana.
“This study is not necessarily providing new information but providing further evidence of the usefulness of Epidiolex in Dravet Syndrome,” says Melissa L Bernbaum, MD, director of neurology at Northwell Health’s Huntington Hospital in Huntington, New York.
She adds that, while there may be a stigma attached to cannabidiol because of the medication’s connection with marijuana, she does not have any patients with such concerns at her practice and in fact, many are interested in “medical marijuana.”
“Parents actually tend to have a positive emotional reaction to the fact that the medication is produced from a plant and then purified, rather than being synthesized in a test tube,” says Miller.
With the benefits of cannabidiol being scientifically proven, GW Pharmaceuticals is seeking the FDA’s thumbs-up for Sativex (naximbols), a spasticity treatment for patients with multiple sclerosis that contains two chemical extracts derived from the cannabis plant. The product is currently approved in 29 countries outside the United States, according to the company.
The company is also exploring cannabinoid-based therapies for autism, spinal cord spasticity, schizophrenia, and post-traumatic stress disorder (PTSD).
Staying Alert to Possible Side Effects
Overall, Epidiolex has a favorable safety profile with notable side effects being the risk of liver enzyme elevations, appetite changes, diarrhea, somnolence (sleepiness), pyrexia (fever), and fatigue.
“It is also important to note potential interactions with other anti-seizure medication,” says Dr. Bernbaum. “Certain combinations may be more likely to cause sedation.”
Schultz stresses that dosing above 25 mg did not significantly improve seizure response, but did increase the number of adverse events. “Given that, it makes sense for the top end of dosing to be around 25 [mg],” he says.
At this time, the sticker cost for the drug is not inexpensive. On average, the price for Epidiolex in the United States for the first year of use was in the $32,000 per year range, according to Schultz, who adds that the out-of-pocket copay may be no more than $25 per patient.
Because dosing depends on patient’s weight, he points out that the product will cost less for young lighter patients and more for older heavier patients.
“Physicians and patients desired a pharmaceutical formulation of a cannabinoid that has gone through proper clinical trials and been tested for safety and efficacy,” says Schultz. “With Epidiolex, they have one that is exactly the same every time that it is taken, and because it is FDA-approved, it will be paid for by insurance.”