Cannabidiol (CBD) is a compound found in the cannabis plant that does not cause the “high” often linked with marijuana. In recent years, researchers have taken a closer look at CBD as a possible option for treating epilepsy, especially when regular anti-seizure medicines are not enough. Although people have used cannabis for medical reasons for thousands of years, government laws like the Marihuana Tax Act of 1937 and the 1970 Cannabis Control Act made research difficult for many decades. This history has shaped how CBD is used in medical settings today.
As more states in the U.S. support legal cannabis for medical and recreational use, scientists have been able to conduct more studies. When it comes to epilepsy, these studies have led to the approval of the first CBD-based drug by the U.S. Food and Drug Administration (FDA). However, some people and doctors are interested in using CBD in ways that the FDA has not specifically approved, which is known as “off-label” use. This article covers both FDA-approved CBD treatments for epilepsy and off-label use, giving a clear view of what patients and caregivers should know.
What is CBD and How Does it Affect Epilepsy?
What is Cannabidiol (CBD)?
CBD is one of many chemicals found in the Cannabis sativa plant. It is different from THC (tetrahydrocannabinol), which is the part of cannabis that causes a “high.” Because CBD does not have this effect, it is more acceptable for medical use, especially for people with conditions where clear thinking is important, such as epilepsy. While THC mostly affects the brain through certain receptors (CB1), CBD does not work strongly on these same pathways.
CBD products on the market can range from homemade oils to well-tested, pharmaceutical-grade options. These differences matter – the effect and safety of CBD can change a lot depending on how pure or controlled the product is. When the FDA approves a product like Epidiolex, it means the drug is made to the same standard each time, which is not always true for products you can buy without a prescription.
How Does CBD Work in the Brain?
Scientists do not fully understand how CBD helps prevent seizures. It does not use the same pathways in the brain as many other anti-seizure drugs. Possible ways it might work include affecting serotonin, certain brain channels (T-type calcium channels), or receptors like NMDA. Animal research shows CBD may “quiet” overactive brain cells, especially those involved in rare childhood epilepsies like Dravet Syndrome. Instead of using just one direct pathway, CBD seems to use several at the same time to help stop seizures.
What Role Does CBD Play in Treating Seizures?
CBD is usually not used as the first or only treatment for epilepsy. Its main use is as an extra drug, or adjunctive therapy, for people who do not get enough help from other epilepsy medications. Clinical studies have shown that CBD can help reduce the number of seizures, especially in severe forms of childhood epilepsy. However, it can sometimes make seizures worse for a small number of people, depending on the seizure type. CBD is best used as part of a plan that includes different approaches, not as a substitute for other treatments.
Which FDA-Approved CBD Treatments Exist for Epilepsy?
Epidiolex: The First FDA-Approved CBD Medication
On June 25, 2018, the FDA approved a CBD-based oral medicine called Epidiolex, made by Greenwich Biosciences. This was the first time a prescription medicine made from CBD got approval in the United States. Before Epidiolex, strict marijuana regulations made medical use and study difficult. Epidiolex went through several studies before approval, and official changes to its legal status made it available by prescription. Its approval was a turning point that also changed how medical authorities view cannabis-derived drugs.
Which Epilepsy Types is Epidiolex Approved For?
Epidiolex can be used for patients age two and older with two rare, severe forms of childhood epilepsy: Dravet syndrome and Lennox-Gastaut syndrome. Dravet syndrome affects about 1 in 16,000 children and includes many types of seizures. Lennox-Gastaut syndrome is even less common but is known for “drop attacks,” which are sudden losses of muscle tone that can cause injury. Both syndromes are very hard to manage with regular medications. In 2020, the FDA also approved Epidiolex for seizures caused by Tuberous Sclerosis Complex (TSC), another rare genetic disorder that can lead to epilepsy.
Research and Effectiveness of Epidiolex
Epidiolex earned FDA approval based on strong evidence from several careful studies. These clinical trials, known as the GWPCARE series, tested Epidiolex for safety and whether it really helped people with Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis Complex. For Dravet syndrome, 42.5% of patients taking CBD had their convulsive seizures cut in half. For Lennox-Gastaut syndrome, people taking the higher dose of CBD had a 21.6% greater reduction in “drop” seizures compared to those given placebo. Caregivers often reported that their child’s overall condition improved, not just the seizure count.
How to Get Epidiolex: Prescription, Dosage, and Cost
- Prescription: Any healthcare provider can prescribe Epidiolex; a special license is not needed.
- Starting Dose: For Dravet syndrome: typically 2.5 mg/kg twice daily (5 mg/kg per day). For Lennox-Gastaut syndrome: usually 1.5 mg/kg twice daily (3 mg/kg per day). The dose can be increased slowly, up to a maximum of 20 mg/kg/day (DS, TSC) or 25 mg/kg/day (LGS).
- Cost and Coverage: Epidiolex is expensive and, while many insurance plans cover it, getting approval for payment can be difficult, especially if used for a reason not specifically approved by the FDA (off-label use). The process often includes paperwork and waiting for approval.
What is Off-Label CBD Use for Epilepsy?
What Does Off-Label CBD Use Mean?
Off-label drug use happens when a doctor prescribes a medication for a situation, dose, or age group that is not listed on the official FDA approval. This happens fairly often, especially for conditions that are rare or for children, whose needs might not be fully covered by the drug’s label. Doctors can use their own judgment, along with published research, to make these choices, especially when patients have few other options.
Why Do Doctors Use CBD Off-Label?
- Extra Approval is Hard and Expensive: Getting the FDA to approve a new use for a drug takes years of research and costs a lot of money.
- Pediatric Patients: Many children are left out of early drug studies. As a result, off-label use is common in pediatric epilepsy.
- Rare Conditions: People with rare epilepsies may not have drugs specifically approved for their type, but small studies or reports may show that a drug like Epidiolex helps.
For example, children with a type of epilepsy called SYNGAP1 may benefit from CBD, according to published studies, even though this use is not officially approved.
What Does the Research Say About Off-Label CBD?
| Condition | Number of Patients | Results |
|---|---|---|
| Genetic Syndromes (CDKL5, Aicardi, Dup15q, Doose) | 55 | Similar effectiveness and safety as in FDA-approved uses |
| Febrile Infection-Related Epilepsy Syndrome (FIRES) | 7 (case series) | CBD helped wean patients off other AEDs after other treatments failed |
These studies suggest CBD may work for other hard-to-treat epilepsies, though more research is needed before official approval.
Legal and Safety Issues with Off-Label Use
- Insurance: Companies usually want proof-a written request and supportive evidence from medical journals-before they pay for drug use not approved by the FDA.
- Safety: Epidiolex is well-studied for approved uses, but less is known when it’s used alongside other drugs or for new conditions. Drug interactions are common, especially with medications like clobazam, diazepam, or clonazepam. Doctors need to monitor patients closely.
- Monitoring: Because data are limited for off-label uses, patients and their caregivers should have regular follow-ups with their doctor to check for side effects or interactions.
How Does CBD Compare to Other Epilepsy Treatments?
CBD vs. Standard Anti-Seizure Drugs
Most people with epilepsy start with traditional anti-seizure drugs (often called AEDs). However, about 30% of people with epilepsy cannot control their seizures with these medications. Side effects from AEDs can be a problem too, such as tiredness, liver problems, and skin rashes.
CBD, especially as Epidiolex, has been shown to help those with certain severe, drug-resistant epilepsies that don’t respond to regular medications. While CBD can have side effects like tiredness, loss of appetite, diarrhea, or changes to liver tests, most of these can be managed by adjusting the dose or monitoring blood tests. CBD is usually not a first option but is sometimes added to help when other medicines are not enough.
Can CBD Be Combined with Other Epilepsy Medicines?
Yes. In most studies and in real life, CBD is added to other anti-epileptic drugs. For example, people using epidiolex with clobazam often had better seizure control. However, combining them can raise the risk of side effects, including increased tiredness or raised liver enzymes, which is why careful monitoring and sometimes dose adjustments are needed. The aim is to use a mix of medicines that controls seizures with as few side effects as possible.
Common Drug Interactions:
- Clobazam: CBD can increase the level of clobazam’s active part in the body, causing more drowsiness.
- Valproate (VPA): CBD together with VPA can cause high liver enzyme levels, so regular blood tests are needed.
When Should Patients Consider CBD?
- If other drugs, diets (like ketogenic diet), devices, or surgeries have not controlled seizures.
- If the patient has Dravet syndrome, Lennox-Gastaut syndrome, or Tuberous Sclerosis Complex.
- After a full check at an epilepsy center and a discussion with a doctor about benefits, risks, and side effects.
The Epilepsy Foundation recommends these decisions be made with a doctor who knows your full medical history.
What Are the Risks and Side Effects of CBD for Epilepsy?
Possible Side Effects of CBD (Epidiolex and Others)
- Sleepiness
- Loss of appetite
- Diarrhea
- Tiredness
- Rash or skin redness
- Sleeping problems
- Infections
Some side effects-such as diarrhea or stomach upset-were seen in both the drug and placebo groups in studies, likely because both contained oil. Most side effects go away on their own or when the dosage is lowered. People using non-FDA-approved CBD products might have more side effects because the content of these products can vary widely.
Can CBD Interact with Other Medications?
Yes. CBD is broken down by certain enzymes in the liver (mainly CYP3A4 and CYP2C19). It can change how other drugs are processed, particularly:
- Clobazam: May build up in the body with CBD, causing more sedation.
- Valproate: Increases the risk of high liver enzymes.
- Other anti-epileptics and medicines (e.g., brivaracetam, tacrolimus) may also interact.
Doctors often order regular blood tests and may adjust medication doses to help avoid problems.
Warnings for Children, Pregnant Women, and Sensitive Groups
- Children: Epidiolex is approved for age 1 and up for some epilepsy types. Long-term effects on development are still being researched.
- Pregnancy: There is little information about CBD safety during pregnancy. Animal tests show some risk, so most experts are careful about using it in pregnant or breastfeeding women unless clearly needed.
- Liver Problems: Anyone with a liver condition or using drugs like valproate will need frequent blood tests.
What is the Current Research on CBD for Epilepsy?
Ongoing Studies and What They Show
Research on CBD for epilepsy is very active. Over 100 studies are registered on the National Library of Medicine website. These cover not only Dravet syndrome, Lennox-Gastaut syndrome, and TSC, but also conditions such as:
- Infantile spasms
- Sturge-Weber syndrome
- Fragile X syndrome
Results from some trials are still coming out, and new studies continue to look at long-term effects, safety, and whether CBD works for even more types of epilepsy.
CBD for Rare Childhood Epilepsies
The earliest and strongest research for CBD has focused on rare, severe childhood epilepsies. Besides the officially approved uses, smaller studies and case reports suggest that it may help in other types-such as CDKL5 deficiency, Aicardi syndrome, Dup15q, and Doose syndrome. Usually, these reports show decreased seizure numbers and other improvements, but larger and more controlled studies are needed.
Synthetic and Other Forms of CBD
Some companies are developing synthetic CBD, which is made in a lab rather than extracted from plants. Supporters say synthetic versions can be made in large amounts, with consistent quality, and without the environmental challenges of growing cannabis. Some studies show these lab-made versions work about the same as plant-based products. There’s debate about whether plant CBD works better due to other natural compounds in the plant (the so-called “entourage effect”), but evidence for this is still limited.
Regulations and Access: What Should Patients Know About Using CBD for Epilepsy?
FDA Guidelines for CBD
The FDA must approve a CBD product for it to be marketed as a medicine in the U.S. To get this approval, a product must go through careful studies to check how it works, how safe it is, what the right dose is, and how it interacts with other medicines. So far, only Epidiolex has gone through this process and been approved by the FDA for epilepsy. Many CBD products available in stores or online have not been tested this way and may not be safe or effective.
State Laws and Medical Cannabis
While the FDA controls prescription drugs like Epidiolex, each state can set its own rules about cannabis and CBD. The 2018 Farm Bill made hemp-derived CBD (with less than 0.3% THC) legal at the federal level, but state laws vary. Over half of states allow some form of medical cannabis, often with their own rules about who can get it, what conditions qualify, and how the process works. Before trying non-prescription CBD products, it’s best to check both state laws and talk to a healthcare provider.
Insurance, Cost, and Access
Epidiolex can be costly, and insurance coverage depends on both the patient’s condition and their insurance company. Here’s a comparison:
| Option | Cost | Insurance Coverage |
|---|---|---|
| Epidiolex (FDA-approved) | High (varies by weight and dose) | Usually covered for approved uses; off-label use may not be covered |
| Standard seizure medications | Lower (on average) | Commonly covered |
For off-label uses, patients may need extra paperwork, letters from their doctor, and sometimes an appeal if coverage is denied.
Frequently Asked Questions about CBD for Epilepsy
Should Patients Try CBD if Other Epilepsy Medicines Don’t Work?
CBD, and especially Epidiolex, is a reasonable next step for people with epilepsy that doesn’t respond to other treatments-mainly for Dravet syndrome, Lennox-Gastaut syndrome, and TSC. However, adding CBD should always be done with guidance from a doctor after other options have been explored.
Can CBD Affect Other Medicines?
Yes. CBD can change the way other drugs are processed, especially certain anti-epileptic drugs. For example, it can raise levels of clobazam or valproate, leading to more side effects. Blood tests and close monitoring by a doctor are important when using CBD with other medications.
How Soon Does CBD Start Working?
In clinical studies, people usually saw fewer seizures within weeks to a few months of starting and adjusting the CBD dose. The dose is slowly increased (“titrated”) to reduce side effects. It takes patience and regular follow-ups to find the right dose for each person.
Are Store-Bought/OTC CBD Products Safe or Effective for Seizures?
Most over-the-counter CBD products are not recommended for treating seizures. These products do not have the same quality controls as FDA-approved medicines. Studies show that OTC CBD often does not contain the amount or type of CBD listed on the label and may even have dangerous contaminants. For epilepsy, use only CBD prescribed by a medical professional (like Epidiolex), not products from a store or the internet.