The New England Journal of Medicine just published more evidence of the effectiveness of cannabidiol (CBD) in treating seizures.
The new study offers the strongest evidence yet of CBD's effectiveness in reducing seizures in severe forms of epilepsy.
Patients taking two different doses of a Epidiolex, an experimental CBD medication manufactured by GW Pharmaceuticals, experienced fewer epileptic seizures and fewer seizures overall, according to study published online by The New England Journal. The trial was funded by GW Pharmaceuticals, which has submitted this medication for FDA approval to treat epileptic seizures.
In addition to a recent FDA committee recommendation and other recent studies showing CBD reduced epileptic seizures, this new study—the first large-scale trial examining the effects of specific CBD medication doses—increases the likelihood of the first cannabis plant-derived medication arriving soon on the U.S. market.
“This new study adds rigorous evidence of cannabidiol’s effectiveness in reducing seizure burden in a severe form of epilepsy and, importantly, is the first study of its kind to offer more information on proper dosing,” co-lead author Orrin Devinsky said in a news release issued by NYU Langone Health, his employer. “These are real medications with real side effects.”
Preventing ‘Drop’ Seizures
Devinsky’s team conducted a phase 3 multi-center, randomized, double-blind, placebo-controlled trial internationally, aiming to assess the efficacy and safety of two different CBD doses and compare them to a placebo. They added the CBD and placebo doses to regimens of traditional anti-epileptic medication prescribed to treat “drop” seizures in patients with the rare but severe Lennox–Gastaut syndrome form of epilepsy.
They measured the resulting drop-seizure frequency. Patients taking a daily high dose (20mg of CBD per kilogram of body weight; e.g., about 1,600mg daily for a 180-pound adult) of the CBD medication while continuing their conventional antiepileptic regimen experienced a median 41.9% percent reduction in seizures after 28 days. Participants taking a lower dose of CBD (10mg per kilogram of body weight) experienced a 37.2% decrease. Patients in a placebo group experienced a 17.2% drop in seizures. Results were statistically significant.
An earlier study published in The Lancet in March 2018 concluded: 'Add-on cannabidiol is effective for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome.'
Researchers also found significant differences when they examined who experienced at least a 50% drop-seizure reduction: 39% of the 20-mg cannabidiol group, 36% in the 10-mg group and 14% in the placebo group. One-quarter of the 20-mg patients experienced at least a 75% reduction, versus 11% of the 10-mg cannabidiol group and 3% in the placebo group.
The median percent reduction in occurrences of all types of seizures was 38.4% in the 20-mg group, 36.4% in the 10-mg group and 18.5% in the placebo group.
“This trial involving children and adults with the Lennox-Gastaut syndrome showed that a pharmaceutical formulation of purified cannabidiol, administered at a dose of either 10 mg or 20 mg per kilogram (of body weight) per day, resulted in a significantly greater reduction in the frequency of drop seizures than placebo,” the authors concluded.
“This landmark study provides data and evidence that Epidiolex can be an effective and safe treatment for seizures seen in patients with Lennox Gastaut Syndrome, a very difficult to control epilepsy syndrome,” said co-author Anup Patel, MD, chief of Neurology at Nationwide Children’s Hospital, according to the release.
FDA Approval Expected in June
Devinsky, an NYU School of Medicine professor who directs Langone’s Comprehensive Epilepsy Center, co-authored a study published in last May’sNew England Journal showing a decrease in monthly seizure frequency in patients with Dravet syndrome, another rare form of epilepsy. Another study published in The Lancet in March concluded: “Add-on cannabidiol is (effective) for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated.” Researchers are extending that trial to assess CBD’s long-term efficacy and safety.
The FDA reviewed some of these studies before an April meeting of its Peripheral and Central Nervous System Drugs Advisory Committee. The committee then heard testimony and recommended Epidiolex for FDA approval as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, via a 13-0 vote.
The FDA is expected to officially decide the medication’s fate by late June, according to Justin Gover, CEO of GW Pharmaceuticals. “We are reviewing this application on an expedited timeline,” an FDA representative said after the committee vote, “working to accelerate this process as much as we can.” The FDA is not obliged to follow the advisory committee’s recommendations, but it often does.
The Secret Formula: It’s CBD
If approved, Epidiolex would become the first medication derived from the cannabis plant allowed in the U.S. The FDA has previously approved synthetic cannabis medications, which more closely resemble tetrahydrocannabinol (THC), but nothing plant-derived nor anything featuring CBD. Sativex, a GW Pharma product that incorporates both THC and CBD, has been approved for medical use outside the U.S.
Epidiolex features a solution of 100 mg/ml of CBD dissolved in sesame oil, ethanol, sweetener, and a flavoring agent, according to the FDA review. The medication is harvested from cannabis plants specifically bred for medical purposes, with high CBD concentration, according to a GW Pharmaceuticals report.
Specific Doses of CBD Used
GW Pharmaceuticals supplied the CBD and placebo used in the new trial, according to the study, and three co-authors have been employees of GW Pharmaceuticals. Devinsky received research funding from GW Pharmaceuticals, according to the NYU release, and a consulting fee for advising during the FDA committee meeting.
His team enrolled 225 patients with Lennox-Gastaut syndrome, randomly assigning them to receive CBD at a dose of either 20 mg per kilogram of body weight per day, the 10-mg dose or placebo. They siphoned 76 participants to the 20-mg group, 73 to the 10-mg cannabidiol group and 76 to the placebo group.
The CBD or placebo was administered orally twice daily, with patients or their caregivers trained to record the number and type of seizures that occurred each day. They also recorded CBD or placebo use, use of concomitant medications, and any adverse events.
Who Was Tested
Patients were eligible if they were between 2 and 55 years old; had an electro-encephalogram showing “a pattern of slow spike-and-wave complexes” (characteristic of the disorder); and had at least two types of generalized seizures—including drop seizures—for at least 6 months.
Patients were taking between 1 to 4 other antiepileptic drugs and had at least two drop seizures each week during the study’s baseline period. The had previously received a median of 6 antiepileptic drugs, which had failed to control the seizures, and were receiving a median of 3 antiepileptic drugs simultaneously when they started the trial.
A majority of the patients were white, from the U.S., and under 18.
Patients were excluded if they had unstable medical conditions during the four weeks before screening, a history of alcohol or substance abuse, or had used recreational or medicinal cannabis over the previous 3 months.
FDA Approval Still Not Assured
LGS and Dravet syndrome are rare, severe, refractory epilepsy syndromes that emerge early in childhood and are linked to higher mortality rates. Medications on the market often do not adequately treat these conditions.
The Epilepsy Foundation applauded the FDA’s April committee vote. “More than a third of people living with epilepsy do not have seizure control, and many more live with significant side effects that impact cognitive ability, mood, and memory,” the Foundation said in a statement issued shortly after the meeting. “Epidiolex represents hope for the many individuals living with intractable seizures and rare epilepsies.”
Still, FDA committee members in April cautioned that more research needs to be done on Epidiolex dosing. Devinsky issued a similar warning in the NYU statement about the new study. “While the news gives hope for a new treatment option to the epilepsy community,” he said, “more research remains imperative to better determine the effects of CBD and other similar cannabis-derived compounds on other forms of the disease and in more dosing regimens.”