Preliminary data on 7 children treated with a medicinal cannabis oil in a Phase 1 study underway in Canada show a safe reduction in seizure frequency. 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. Cannabis oil has been gaining ground as a treatment for seizures in children. But is it safe? Here's more from Dell Children's Medical Center in Austin.
Cannabidiol Oil Safely Lessens Seizures in Treatment-resistant Children, Early Trial Data Show
Severe epilepsy in children with Dravet and Lennox-Gastaut syndrome can be safely treated with a medicinal cannabis oil that includes, at low dose, the intoxicating compound in marijuana known as THC, preliminary results of a Phase 1 clinical study suggest.
“What makes these results really exciting is it opens up as a treatment option for kids who have failed to respond to traditional medications,” said Richard Huntsman, MD, pediatric neurologist and lead author of the study, said in a news release.
Increasing evidence suggests that non-psychotropic cannabis-derived compounds, such as pharmaceutical grade cannabidiol (CBD), can help to manage seizures in children with treatment-resistant epilepsy. But little guidance exists for doctors on the proper concentration and dosing of CBD and other cannabinoids, as well as on their pharmacological characteristics.
“The resultant inability to provide evidence-based dosing and therapeutic monitoring of cannabis-based products in children … leads to a reluctance by many physicians to authorize CBD-enriched cannabis herbal extract to these patients,” the researchers wrote.
A team led by researchers at University of Saskatchewan, Canada, are conducting an open-label Phase 1 clinical study (NCT03024827) called CARE-E. Scientists are exploring the safety and impact of increasing doses of CBD-enriched cannabis herbal extract (CHE) used as add-on therapy in up 28 children (ages 1 to 10) with epileptic encephalopathy resistant to standard anticonvulsant therapy. The mixture, called CanniMed 1:20, contains 1 mg/ml of THC and 20 mg/ml of CBD.
The trial is still recruiting at clinical sites in British Columbia, Manitoba, Quebec and Saskatchewan. More information is available here.
Data on the first seven children, four with Dravet syndrome and three with Lennox-Gastaut, enrolled at the University of Saskatchewan’s clinical site made up this report.
All started CHE treatment with an initial CBD dose of 2–3 mg/kg per day. Over the following three months, the dose was increased every four weeks up to a maximum of 10–12 mg/kg per day. Children were then weaned off CHE over their final month of trial participation.
Caregivers were asked to monitor and record daily seizure frequencies throughout the study.
All seven children had fewer seizures while taking CHE at a CBD equivalent dose of 5–6 mg/kg per day, data showed. Six experienced a 25% drop in seizure frequency and four a decrease of more than 50%.
At the maximum tested dose (10–12 mg/kg per day), CHE led to an average seizure reduction across all children of 74%, with three being seizure free.
After the weaning period, these children continued to experience fewer seizures compared to pre-treatment, without any changes in their anti-convulsant treatment regimen.
In general, CHE with CBD equivalent dose of 10–12 mg/kg per day was found to lower electrical activity in the brain, as determined by electroencephalography (EEG).
“The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when a 1:20 THC:CBD CHE is used,” the study concluded. “The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.”
Better quality of life was also reported, with greatest improvements being on the cognitive, social and emotional functioning subscales of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55).
“Some of the improvements in quality of life were really dramatic with some of the children having huge improvements in their ability to communicate with their families. Some of these children started to talk or crawl for the first time. They became more interactive with their families and loved ones,” Huntsman said.
Data also showed the treatment was generally safe and well-tolerated.
Most common adverse reactions reported were occasional episodes of nausea and vomiting, diarrhea, increased appetite, difficulty sleeping, and spasticity (uncontrolled muscle movement and/or contraction). No clinically significant events were directly attributed to treatment with CHE.
Although the benefits of CHE seemed to be associated with the relative CBD dose, analysis of its metabolism in the body suggested a potential saturation effect with increased oral bioavailability in some patients. This finding suggests the “need to limit dose sizes and not to simply continue increasing doses until an appropriate effect is observed,” the researchers wrote.
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.”
Could Cannabis Oil Help Ease Seizures in Children?
There are many treatments for seizures in children, but not all children respond to one or more of them. Cannabis oil is a new and sometimes controversial treatment that is currently gaining ground as a natural and non-invasive way to keep seizures under control.
Cannabis is the proper name for marijuana, a cousin of the hemp plant and one that has long been classified as an illegal substance. However, with many states now opting to legalize cannabis for medical use, research is being conducted on how it can be used to treat seizures in children with epilepsy.
How Does Cannabis Oil Benefit?
Far from being the stereotypical drug that makes a person want to eat snacks and watch television all day, cannabis contains chemicals that are able to work with the body to ease seizures. The two major components of cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD).
THC is the component of cannabis that produces the characteristic euphoric state often referred to as a “high.” Cannabidiol does not produce psychoactive effects, but has been shown to promote positive effects in different parts of the body. Cannabidiol is the component in cannabis that is hypothesized to ease seizures in children.
Even if you live in an area where cannabis has been legalized, you should still consult with your child’s doctor before trying cannabis oil to treat their seizures.
Is Cannabis Oil Safe?
Cannabis oil that contains very low amounts of THC or none at all is preferred for use as medicine. This oil can be made from both marijuana and hemp plants. Hemp strains often contain CBD without THC.
Although marijuana has been shown to be habit-forming, it is not addictive. Its habit-forming properties are usually associated with the effects of THC on a person. Cannabis oil that contains little or no THC is typically not habit-forming.