Dravet Syndrome and CBD
There is a great deal of controversy over CBD, with the FDA still not confirming a stance on it and no official recommendation about its use. There are very few exceptions to this rule, one of which is Dravet syndrome. This syndrome is one of the very few cases in which the FDA acknowledges the benefits CBD and has even approved a medication containing CBD. To date, the remedy for Dravet syndrome with CBD is the only cannabis-based medication with FDA approval.
Given this unique status, those in favor of CBD accessibility and cannabis legalization should familiarize themselves with Dravet syndrome and the positive effects that CBD can have on the condition.
What Is Dravet Syndrome?
Dravet syndrome was previously called Severe Myoclonic Epilepsy of Infancy (SMEI) and is sometimes still referred to by that name. It is a rare and catastrophic seizure condition that lasts for life.
The condition affects one out of every 15,700 individuals, and about 80 percent of those patients have mutations of the SCN1A gene.
Symptoms
Seizures are the main symptom of Dravet syndrome, with signs typically appearing within a child’s first year. The seizures are usually prolonged and frequent.
In addition to the frequent and prolonged seizures, many patients with Dravet syndrome will experience other symptoms. It is common for comorbidities with abnormal EEGs or development delay to occur when the patient is one or two years old. Some of the other common symptoms of those with Dravet syndrome are:
- Developmental and behavioral delays
- Balance and movement issues
- Delayed speech and language issues
- Orthopedic conditions
- Chronic infections
- Sleeping difficulties
- Sensory integration disorders
- Dysautonomia (disruptions of the patient’s autonomic nervous system), which can lead to issues such as problems regulating heart rate, body temperature, and blood pressure
There is also a mortality rate of 15 to 20 percent with Dravet syndrome because of seizure-related accidents, prolonged seizures, infections, and SUDEP (Sudden Unexpected Death in Epilepsy).
Current Treatments
There is not currently any cure available for Dravet syndrome, with doctors instead working to reduce the seizures. Most patients will start with anti-seizure medications such as clobazam and valproic acid. From there, they may try stiripentol, topiramate, or the ketogenic diet. As a third-line treatment, doctors recommend clonazepam, levetiracetam, zonisamide, ethosuximide, and vagal nerve stimulator.
Unfortunately, none of these treatments works with a high level of consistency. Even with anti-seizure medications, most patients with Dravet syndrome will still experience seizures.
Understanding CBD
CBD or cannabidiol is one of the over a hundred cannabinoids that naturally occur in cannabis. CBD is a non-psychoactive chemical compound, so this natural compound will not get consumers high. That high comes from THC or tetrahydrocannabinol.
Some early research indicates that CBD may have potential benefits, including the ability to treat Dravet syndrome, or at least reduce its symptoms.
FDA Approval of CBD-based Medication
As mentioned, Dravet syndrome is unique in that it is one of the rare conditions for which the Food and Drug Administration has approved a cannabis-based medication. This medication is called Epidiolex and is a CBD oral solution. In addition to receiving FDA approval to treat Dravet syndrome, it is also approved to treat Lennox-Gastaut syndrome, another rare and catastrophic seizure disorder that affects children.
The Timeline and Details
The FDA approved Epidiolex on June 25, 2018, for patients with Dravet syndrome or Lennox-Gastaut syndrome who are at least two years old.
What the FDA Said at the Time
The FDA approval of Epidiolex was a historic event as it was the very first CBD medication to be approved, and it remains the only one so far at the time of writing. As such, the FDA was sure to comment on the situation. Scott Gottlieb, M.D., the FDA Commissioner, referred to the approval of the drug as a reminder that advancing programs to evaluate marijuana’s active ingredients could help create new medical therapies. He also reaffirmed the commitment of the FDA to that type of research in the future.
The Center for Drug Evaluation and Research’s Division of Neurology Products director (also part of the FDA), Billy Dunn, M.D., pointed out that this was the very first drug approved for use to treat Dravet syndrome. As such, it is a crucial step in caring for patients who have this condition.
Scientific Evidence Clearly Shows the Benefits of CBD for Dravet Syndrome
The FDA approval of the drug for Dravet syndrome, as well as Lennox-Gastaut syndrome, was the result of scientific studies that clearly showed the ability of the medication to reduce seizures. There were controlled clinical trials that confirmed the drug was safe and effective. This is a critical step in FDA approval of any drug, and no steps were skipped when approving Epidiolex. This type of uniform testing gives patients and their parents confidence that they will receive proper dosing and not have to worry about dangerous side effects.
The Main Test From the FDA
The main FDA study examined 516 patients who had either Dravet syndrome or Lennox-Gastaut syndrome. There were three trials that were double-blind, randomized, and placebo-controlled. They involved the patients taking CBD with other medications.
The results indicated that CBD could reduce the frequency with which seizures occurred when compared with a placebo.
2018 Study in Neurology
A study published in Neurology in 2018 looked at patients from 4-10 years old. They received either twice-daily 5, 10, or 20 mg/kg/day doses of CBD or a placebo. There was a four-week baseline period, followed by a three-week treatment period, a 10-day taper, and a four-week follow-up. There were only 32 patients who finalized the treatment, so the sample size is relatively small.
Researchers measured the levels of antiepileptic drugs and CBD levels at the beginning and the end of the treatment. They also used physical examinations and other methods of assessing safety outcomes. The resulting findings indicated that CBD, as well as its metabolites, do not seem to interact with antiepileptic drugs and seem to be safe for young patients with Dravet syndrome.
A 2019 Study
In 2019, another study regarding CBD and Dravet syndrome was published, this time led by Ian Miller, M.D., who is the Comprehensive Epilepsy Program’s medical director at Nicklaus Children’s Hospital in Miami.
This was a randomized study that included nearly 200 patients, all of who were children with Dravet syndrome. The participants were taking an average of three antiepileptic drugs and had previously discontinued an average of four.
Participants either received a placebo, 10 milligrams of CBD per kilogram per day, or 20 milligrams of CBD per kilogram per day. Those receiving 10 mg/kg/day experienced a 56 percent reduction in their baseline of total seizures, and those who received twice that does have a 47 percent reduction. By contrast, the placebo group had a decrease of 30 percent.
The study also saw reductions in seizures that featured convulsions by 49 percent, 46 percent, and 27 percent for the 10 mg/kg/day, 20 mg/kg/day, and placebo groups, respectively.
The study indicated that the ideal dose for treating Dravet syndrome is likely 10 milligrams per kilogram per day, which is in line with the previous research.
There were some adverse effects from participants in the study, but the rates were similar among patients who received CBD and the placebo, at 88, 90, and 89 percent, respectively. The most common of the adverse effects were diarrhea, sleepiness, and decreased appetite. Serious adverse effects only occurred in 20, 25, and 15 percent of the patients.
Another 2019 Study
A separate study regarding Dravet syndrome started with the baseline median frequency of convulsive seizures at 12.4 per month. This dropped by 6.5 for those who received treatment with CBD but just 0.8 with the placebo group. Additionally, that study found that 43 percent of patients who took CBD experienced a 50 percent reduction in seizures compared to only 27 percent in the placebo group.
Potential Side Effects
The clinical trials involving using CBD to treat Dravet syndrome and Lennox-Gastaut syndrome did show some potential side effects, but most of them were mild. They were not enough to cause the FDA to second-guess its decision to approve the medication.
The most common side effects from the clinical trials included: lethargy, sleepiness, sedation, elevated liver enzymes, diarrhea, rash, decreased appetite, malaise, weakness, fatigue, sleep disorder, insomnia, poor-quality sleep, and infections.
The official FDA study also cautioned that risks associated with CBD could include suicidal thoughts or attempts, agitation, depression that is new or worsening, panic attacks, aggression, and liver injury. The last of these could lead to vomiting, nausea, fatigue, anorexia, abdominal pain, dark urine, and jaundice.
The Effects Are Worth It
Given the severity of Dravet syndrome and the fact that so few treatments exist, most of which provide limited results, experts, including those at the FDA, agree that the potential effects are worth it. This is particularly true given that the possible side effects of CBD for Dravet syndrome are much milder than the potential side effects associated with many other FDA medications.
The Importance
The ability of CBD to reduce the frequency and severity of seizures associated with Dravet syndrome is a milestone in the medical world as well as in the push for cannabis legalization.
Shows the Usefulness of CBD
It shows that cannabis and its compounds do have at least some therapeutic potential, which should hopefully encourage further research on the matter.
Provides a Dravet Syndrome Treatment
Patients dealing with Dravet syndrome finally have a treatment that they can try in hopes of results. As the first Dravet-specific medication approved by the FDA, Epidiolex is a significant advancement in treating and controlling this condition. This provides patients and their parents with hope, where that hope was previously in short supply.
Opens the Door for More Research
Those in favor of cannabis legalization or at least its legalization for medical uses see its proven abilities to treat Dravet syndrome as a step in the right direction. Experts hope that the proof of one use of CBD encourages approval for researchers to test the ability of CBD to treat other conditions.
Some experts, for example, feel that because Dravet syndrome and Lennox-Gastaut syndrome are neurological disorders, CBD may have the potential to limit symptoms of other neurological conditions, including multiple sclerosis and epilepsy.
Even with the hope for future research, it is challenging for scientists to gain approval to conduct that research, due to legal issues. A significant part of this issue is that cannabis is a Schedule I drug, a classification that means it has no medical purpose and makes testing its potential medical benefits nearly impossible since research proposals are unlikely to be approved. As such, we may still have to wait several years for similar research into CBD’s ability to treat other conditions. Or, researchers will have to conduct their studies in other countries that have fewer restrictions on cannabis and CBD.
The Takeaway
Dravet syndrome is a severe seizure condition that affects children, typically starting when they are less than one year old. It involves frequent, catastrophic seizures, and there is no known cure. Before research into CBD, there were no FDA-approved medications specifically designed to treat Dravet syndrome. Instead, patients relied solely on anti-seizure medications, dietary changes, and other therapies.
Epidiolex changed this, as it contains CBD. The FDA approved Epidiolex for treating Dravet syndrome as well as another rare childhood seizure disorder, Lennox-Gastaut syndrome. This marks not only the first approved drug to treat Dravet syndrome in particular but also the first time that the FDA approved a drug containing a cannabis derivative in the form of CBD.
Multiple studies indicate that CBD can indeed reduce the seizures associated with Dravet syndrome and do so with minimal adverse effects, at least compared to traditional pharmaceutical medications. Those studies led to the FDA approval of the drug.
Those who support the use of CBD hope that this FDA approval will encourage future research to take place on the potential benefits of CBD and medical marijuana in treating other conditions.
Sources:
https://www.medscape.com/viewarticle/912498