CBD Oil for Treating Epilepsy
KIDS WITH CATASTROPHIC epilepsy can experience numerous weekly, or even daily seizures – despite taking multiple medications to treat their epilepsy. And parents whose children have frequent, debilitating seizures are anxious for other options.
Families and patients trying to manage epilepsy have explored whether cannabidiol, a chemical in marijuana plants, could help. They’ve turned to dispensaries or online sources selling CBD oil of unknown strength or safety. But some products do not contain the levels of CBD they claim, if any, when tested, according to the Food and Drug Administration. Products that do contain CBD may pose risks such as liver injury or interactions with other drugs that should be monitored.
As of only recently, a minority of patients with severe epilepsy can be prescribed an official CBD drug that’s now on the market. In June 2018, the FDA approved a cannabidiol prescription medication for the first time. Called Epidiolex, it’s approved specifically to treat seizures in two rare, severe forms of child-onset epilepsy in patients who are 2 and older. Epidiolex was developed by the British company GW Pharmaceuticals and its U.S. subsidiary Greenwich Biosciences.
Epidiolex is not necessarily a wonder drug: Not everyone who uses it responds. But some patients who take it as a part of their epilepsy medication regimens are experiencing significantly fewer seizures than they did before.
Dr. Orrin Devinsky, a professor of neurology, neurosurgery, and psychiatry at the NYU Grossman School of Medicine and director of NYU Langone’s Comprehensive Epilepsy Center, led studies, with grant support from GW Pharmaceuticals, that bolstered FDA approval of the CBD drug.
“The approval of Epidiolex or cannabidiol is a landmark in medicine,” Devinsky says. “A plant that has been used medicinally for probably well over 5,000 years has finally had one compound extracted from it and now is available to patients. It’s the first time such a medication, based on a cannabis plant, has been approved and scientifically established to be an effective treatment in the United States.”
Part CBD’s novelty is that it affects the nervous system through a different route than other antiepileptic drugs. Although CBD’s action is still not fully understood, Devinsky says, “We do understand some of the ways in which it helps control seizures (by working) on a receptor system that no other drug touches.”
Receptors on the surface of every nerve cell receive messages from chemicals produced within the body, called neurotransmitters. Seizures can occur as specific receptors, called the GPR55 receptors, are stimulated and lose their inhibition, Devinsky explains. “Unfortunately, when a seizure occurs, it leads to an increase of these receptors on nerve cells,” he says. “So it’s a perfect storm of a positive feedback loop.”
Cannabidiol blocks GPR55 receptors. Therefore, Devinsky says, “For the patients for whom this receptor is probably relevant in their epilepsy, CBD can be a very effective drug.”
Approved for Catastrophic Epilepsy
Epidiolex is approved to treat two types of epilepsy: Dravet syndrome and Lennox-Gastaut syndrome. Both are considered to be “catastrophic” epilepsy in that patients have multiples seizures in spite of taking multiple medications and these uncontrollable seizures often have a profound effect on their physical and mental development, quality of life and life expectancy.
- Dravet syndrome. This type of epilepsy begins in the first year of life of an otherwise healthy baby. Once it arises, usually with a lengthy seizure combined with fever, the condition is lifelong. Dravet syndrome is caused by a mutation in the SCN1A gene, according to the Genetic and Rare Diseases Information Center of the National Institutes of Health. Children with Dravet syndrome have frequent and sometimes multiple types of seizures including focal seizures, which start in one area of the brain, and generalized convulsions. Seizures typically are not well-controlled by medication. Children may be placed on a strict medical ketogenic diet, which sometimes helps manage the condition when medications alone aren’t enough.
- Lennox-Gastaut syndrome. This severe form of epilepsy is typically first detected during infancy or early childhood, usually between 3 to 5 years old. Underlying conditions causing Lennon-Gastaut, such as brain malformations or inherited genetic conditions, can sometimes be identified. Cognitive problems and delays in development, such as taking longer to learn to sit, crawl or walk, can occur. Children with Lennox-Gastaut can have several types of seizures: tonic seizures with sudden muscle stiffness; atonic seizures, or “drop attacks,” with sudden loss of muscle tone; and clonic seizures with sustained jerking of the body or body parts. Atypical absence seizures involve staring spells in which people can only partially respond to others, and movements such as blinking, chewing and lip smacking. Intellectual disabilities affect many people with Lennox-Gastaut syndrome. In addition to medications, treatment may include the ketogenic diet, vagus nerve stimulation implants, which send mild electrical pulses to the brain to prevent seizures, and epilepsy surgery.
Research supported by GW Pharmaceuticals involving adults and children with Dravet or Lennox-Gastaut syndrome produced results that ultimately led to FDA approval. Participants received either CBD or a similar-appearing sham or placebo treatment. Neither the participants nor the researchers knew who was getting placebo or getting CBD. These randomized, double-blind, placebo-controlled studies are considered the gold standard of clinical trials because they include a comparison treatment and are less likely to lead to bias.
A 2017 study focused on Dravet syndrome published in the New England Journal of Medicine included 120 children and young adults with the condition who were having drug-resistant seizures. Along with standard antiepileptic treatment, all participants were randomly assigned to receive either a 20 milligram per kilogram (of body weight) daily dose of cannabidiol oral solution (given in two separate doses) or a placebo solution for a 14-week trial period.
On average, convulsive seizures decreased from nearly 13 seizures to about 6 seizures per month with cannabidiol. The average change was from nearly 15 to about 14 seizures per month with the placebo. A minority of patients became seizure-free: 5% in the cannabidiol group but none in the placebo group. Side effects were more common in the cannabidiol group, including diarrhea, vomiting, fatigue, fever, decreased appetite and drowsiness. Abnormal results of blood tests for liver function were also more common in the cannabidiol group.
Results from a study focused on Lennox-Gastaut were published a year later the NEJM in 2018. Conducted at 30 clinical centers, it enrolled 250 participants ranging from 2 to 55 years old, who had at least two drop seizures per week when the study began. All participants were randomly assigned to receive either a lower or higher cannabidiol dose (both based on body weight) or a matching placebo in two daily doses for 14 weeks.
Overall, the average reduction in drop-seizure frequency during the treatment period was nearly 42% in the higher-dose cannabidiol group, about 37% in the lower-dose cannabidiol group and 17% in the placebo group.
Side effects similar to what participants in the Dravet syndrome study experienced occurred more frequently in higher-dose group. Six patients in the higher-dose group and one patient in the lower-dose group discontinued the medication because of side effects and withdrew from the trial.
Research for Other Types of Epilepsy
Dr. Martina Bebin, a professor of neurology and pediatrics with the UAB Epilepsy Center at University of Alabama at Birmingham, is the principal investigator for the pediatric arm of an expanded-access CBD study of 132 participants, both adults and children, with various types of treatment-resistant epilepsy.The study also received support from Greenwich Biosciences.
The study, which was launched in 2015, required the passage of state legislation that authorized the epilepsy center and Children’s of Alabama to conduct research on the then-illicit drug cannabidiol. This legislation was nicknamed Carly’s Law after the little girl who inspired it and who was having multiple seizures a day due to a genetic condition called CDKL5 deficiency disorder.
Study participants had their number and severity of seizures tracked every two weeks throughout the 48-week study. Overall, from the start, the average seizure frequency per study group dropped from 144 seizures to 52 seizures per two-week period, according to results published in the October 2018 issue of the journal Epilepsy & Behavior. In addition, participants experienced less-severe seizures than before they began taking the CBD medication.
“What we know now, four years later, has really helped guide the recommendations of how I use it,” Bebin says. “It certainly has value for some patients. It’s really made a remarkable impact on their seizure control versus other traditional medications that they have tried in the past.”
The yearly cost of Epidiolex is about $32,500 a year, according to multiple news reports of an August 2018 company call with investors. Insurance and Medicare may cover some of the costs for patients with indicated conditions. Some patients may qualify for prescription assistance programs that help defray the cost.
For perspective on what it means to now have a mainstream CBD drug, Dr. Jerry Shih, director of the Epilepsy Center at UC San Diego Neurological Institute, describes what came before.
About six years ago, media coverage focused on a little girl named Charlotte Figi, of Colorado. Charlotte was suffering from multiple daily seizures related to Dravet syndrome, despite treatments including standard anti-seizure drugs. Her parents turned to therapeutic hemp oil with CBD in hopes it would help – and her seizures were dramatically reduced. (The CBD brand “Charlotte’s Web” is named after her.) Eventually, Paige Figi, her mother, founded the nonprofit Coalition for Access Now, which advocates for the legalization of hemp oil.
A growing movement of patients and parents, convinced that CBD could help reduce otherwise intractable seizures, have sought the drug wherever they could find it. Some families moved to Colorado so their kids could get CBD for seizures, Shih says. California residents also took notice, he adds. “Because CBD and marijuana are legal in the state of California, many patients were going to dispensaries and getting off-the-shelf CBD and medical marijuana.”
However, because the manufacturing process and consistency of non-prescription CBD products varies, physicians treating patients with epilepsy have reservations about their use. “I and many others have concerns about the quality of some of the compounds that are sold in the dispensaries,” Shih says. “They may be very good; they may not be very good. The quality control process is obviously not the same as with a pharmaceutical company.”
In that respect, the arrival of Epidiolex made a difference, Shih says. “The fact that the FDA had gone ahead and approved CBD was a big positive in terms of allowing what I call pharmaceutical-grade, pure CBD to be available.”
Bebin also stresses the importance of families understanding the difference between an FDA-approved drug like Epidiolex versus a product they can get through a health food store or online. “As a physician, I have much more confidence in something that has gone through the rigor of an FDA approval because I know what I’m getting,” she says. “The safety of it has been tested.”
The concept of CBD as a natural drug is appealing to many people. However, “I always tell my patients: This is a chemical,” Shih says. “It may come from the marijuana plant, but it’s a chemical and it has certain properties.”
CBD does not produce euphoria, unlike products containing THC, which is the marijuana component that causes a high. CBD does have side effects, emphasizes Shih, who notes that the plan of care for patients who take CBD includes monitoring them for any evidence of liver damage.