U.S. Food and Drug Administration
FDA News Release
The U.S. Food and Drug Administration today approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older. This is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It is also the first FDA approval of a drug for the treatment of patients with Dravet syndrome.
CBD is a chemical component of the Cannabis sativa plant, more commonly known as marijuana. However, CBD does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC).
It is THC (and not CBD) that is the primary psychoactive component of marijuana.
“This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies. And, the FDA is committed to this kind of careful scientific research and drug development,” said FDA Commissioner Scott Gottlieb, M.D. “Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring marijuana-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes. We’ll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products. But, at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”
Dravet syndrome is a rare genetic condition that appears during the first year of life with frequent fever-related seizures (febrile seizures). Later, other types of seizures typically arise, including myoclonic seizures (involuntary muscle spasms). Additionally, status epilepticus, a potentially life-threatening state of continuous seizure activity requiring emergency medical care, may occur. Children with Dravet syndrome typically experience poor development of language and motor skills, hyperactivity and difficulty relating to others.
Lennox-Gastaut syndrome begins in childhood. It is characterized by multiple types of seizures. People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5. More than three-quarters of affected individuals have tonic seizures, which cause the muscles to contract uncontrollably. Almost all children with Lennox-Gastaut syndrome develop learning problems and intellectual disability. Many also have delayed development of motor skills such as sitting and crawling. Most people with Lennox-Gastaut syndrome require help with usual activities of daily living.
“The difficult-to-control seizures that patients with Dravet syndrome and Lennox-Gastaut syndrome experience have a profound impact on these patients’ quality of life,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition.”
Epidiolex’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials involving 516 patients with either Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex, taken along with other medications, was shown to be effective in reducing the frequency of seizures when compared with placebo.
The most common side effects that occurred in Epidiolex-treated patients in the clinical trials were: sleepiness, sedation and lethargy; elevated liver enzymes; decreased appetite; diarrhea; rash; fatigue, malaise and weakness; insomnia, sleep disorder and poor quality sleep; and infections.
Epidiolex must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. As is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks. Epidiolex also caused liver injury, generally mild, but raising the possibility of rare, but more severe injury. More severe liver injury can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice and/or dark urine.
Under the Controlled Substances Act (CSA), CBD is currently a Schedule I substance because it is a chemical component of the cannabis plant. In support of this application, the company conducted nonclinical and clinical studies to assess the abuse potential of CBD.
The FDA prepares and transmits, through the U.S. Department of Health and Human Services, a medical and scientific analysis of substances subject to scheduling, like CBD, and provides recommendations to the Drug Enforcement Administration (DEA) regarding controls under the CSA. DEA is required to make a scheduling determination.
The FDA granted Priority Review designation for this application. Fast-Track designation was granted for Dravet syndrome. Orphan Drug designation was granted for both the Dravet syndrome and Lennox-Gastaut syndrome indications.
The FDA granted approval of Epidiolex to GW Research Ltd.
FDA approved Epidiolex (cannabidiol) oral solution, the first drug comprised of an active ingredient derived from marijuana, to treat two rare and severe forms of epilepsy.
How Can Whole-Plant CBD Oil and FDA-Approved Epidiolex Reduce Seizures?
One of the biggest roadblocks to treating any condition with cannabis medicine is restricted access. Even individuals with medical marijuana cards and approved conditions can still have trouble obtaining the treatment they seek due to haphazard state laws and a lack of federal regulation.
On June 25, 2018, the Federal Drug Administration (FDA) approved the first medication made of a cannabis-derived ingredient to treat severe forms of epilepsy.
Several key studies led to federal approval of Epidiolex as a legal, obtainable treatment option for people suffering from severe forms of epilepsy including Dravet syndrome and Lennox-Gastaut syndrome, both of which cause frequent and dramatic seizures in children.
However, Epidiolex is just one potential cannabis-based treatment for epilepsy, and other studies have examined how whole-plant cannabidiol (CBD) oil may work better as the treatment does not trigger side effects that some patients have experienced with Epidiolex, such as diarrhea.
“ Cannabinoids in the treatment of epilepsy: Hard evidence at last?” is a 2017 study published in the Journal of Epilepsy Research that answered the question with optimistic findings. Researchers found that patients with Dravet and Lennox-Gastaut syndromes responded well to CBD treatment with a decrease in epileptic seizures observed in significantly more patients in the control groups than in the placebo groups.
Emilio Perucca, the author of the study, wrote: “These are exciting times for research in cannabinoids. After almost four millennia of their documented medical use in the treatment of seizure disorders, we are very close to obtaining conclusive evidence of their efficacy in some severe epilepsy syndromes. The era of evidence-based prescription of a cannabis product is within our sight.”
Perucca’s crystal ball was accurate, as Epidiolex received FDA approval the following year. That same year, a 2018 study published in the New England Journal of Medicine focused on Lennox-Gastaut syndrome and patients whose seizures had been unresponsive to their prescribed anti-epileptic medications. When treated with 20 milligrams of CBD, nearly 42 percent experienced a reduction in seizures, while 10 milligrams of CBD lessened seizures in 37 percent of individuals. Similar to the results of the 2017 study, the placebo group patients experienced lower levels of seizure reductions than the control group.
But Epidiolex is not a one-size-fits-all treatment, and some patients have reported adverse effects. A 2015 study of single compound vs. whole-plant CBD could provide some insight as to why Epidiolex can be problematic. Epidiolex is made from isolated, single-molecule CBD, while CBD oils are made of whole plant cannabinoids. Researchers found that the whole plant model is more effective than single-molecule CBD.
The Israeli team of researchers who conducted the study stated: “A lot of research has been made to isolate and characterize isolated single constituents of traditional herbal medicine to find their rationale for therapeutic uses. However, our data together with those of others provide legitimation to introduce a new generation of phytopharmaceuticals to treat diseases…”
Specific to treating epilepsy, a 2018 study published in the journal Epilepsy Behavior showed how whole-plant CBD oil has been associated with reduced epileptic seizures in pediatric patients, with 10% becoming completely seizure-free. As sedation was the most common side effect reported in less than 4% of study participants, researchers determined that CBD oil can reduce seizures with minimal adverse effects.
At one time, Armand Sahyoun’s epileptic seizures were so dangerous that he could not cross the street or use the stairs. Armand’s mother, Beth, shared with Weedmaps News how she had even been contemplating brain surgery for her son to stop his seizures. But then they discovered whole-plant CBD oil and such a drastic measure was no longer necessary.
Today, 24-year-old Armand, who also was diagnosed with autism , has experienced a complete turnaround as he uses CBD oil under the treatment of Dr. Bonni Goldstein, medical director of Canna-Centers in Lawndale, California .
“Armand is doing things now that we did not think were possible. He is quite an athlete and very active in Special Olympics,” Beth Sayhoun stated in an email interview with Weedmaps News. “His quality of life with CBD is dramatically improved.”
While CBD helps with Armand’s physical symptoms, THC has boosted his mood and morale. Beth Sayhoun explained, “The seizure pharmaceuticals made Armand’s moodiness and anxiety much worse. He was a very morose person, and tended to be depressed and very tired. The THC has definitely helped with these issues. He started at about 4 milligrams per pay, and is now up to 10 milligrams per day. He does not appear ‘stoned’ at all, but his mood is lighter, and he seems to be happier.”
As his cannabis dosage increases, Armand has been weaning off the seizure medications that made him depressed. Beth Sayhoun stated, “It takes time and tenacity. We are so much more comfortable with Armand using a plant-based medicine over an Rx.”
For other patients, Epidiolex has been the answer. Molly Hendershot has suffered from epileptic seizures since she was four months old, according to her mother, Allison, who was interviewed on CBS News in 2018. Now 13, Molly swallows Epidiolex in the palatable form of a strawberry-flavored syrup to manage her seizures. Before Epidiolex, the Rochester, New York -based family was considering relocation to Colorado to have legal access to marijuana.
Ultimately, Molly’s mother was glad to stay put and have the FDA-approved medicine as a choice: “ I preferred this to some of those other options because it’s a commercial product that has gone through rigorous testing,” Allison told CBS News.
What the Experts Say
Will the FDA approve other cannabis-based drugs in the future?
The possibility is strong, as FDA commissioner Scott Gottlieb stated in the 2018 press release for Epidiolex : “We’ll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high-quality products.”
For now, physicians treating patients with epilepsy have one FDA-approved treatment and a spectrum of whole-plant CBD oils to choose from. Many of the patients who have experienced positive outcomes with whole plant CBD oil were resistant to other forms of treatment, Goldstein shared.
Regarding her patients, Goldstein told Weedmaps News: “The majority have some beneficial response with no negative side effects. The advantage over Epidiolex is that many of the other compounds in CBD-rich cannabis are also anti-convulsant and may help to decrease seizures.”
Through Epidiolex or whole-plant CBD oil, cannabis seems to be an effective solution for some epilepsy patients.
The Bottom Line
With an FDA-approved medication and whole-plant CBD oils already on the market, cannabis has proven effective in reducing seizures and therefore improving the quality of life of patients coping with rare forms of epilepsy.
How Can Whole-Plant CBD Oil and FDA-Approved Epidiolex Reduce Seizures? One of the biggest roadblocks to treating any condition with cannabis medicine is restricted access. Even individuals with