Cbd oil for refractory seizures

Cannabidiol (CBD) for Epilepsy Treatment

Epidiolex, a precription form, is approved for some seizures

Heidi Moawad is a neurologist and expert in the field of brain health and neurological disorders. Dr. Moawad regularly writes and edits health and career content for medical books and publications.

Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.

Meredith Bull, ND, is a licensed naturopathic doctor with a private practice in Los Angeles. She helped co-author the first integrative geriatrics textbook, “Integrative Geriatric Medicine.”

Cannabidiol (CBD)—a component of the marijuana plant—has gotten a lot of attention for medical use, including the treatment of epilepsy. Epidiolex is the only prescription form of CBD available, and it was approved by the U.S. Food and Drug Administration (FDA) in June 2018 for the treatment of seizures in two hard-to-treat forms epilepsy—Lennox-Gastaut syndrome (LGS) and Dravet syndrome. Epidiolex is approved for adults and children over the age of 2 who have one of these rare disorders.

How It Works

Seizures are caused by erratic electrical activity in the brain that can spread and cause uncontrolled physical movements and/or alterations of consciousness. Most anti-seizure drugs work by slowing down excitatory nerve activity in the brain.

However, LGS and Dravet syndrome may be treated with medications that aren’t commonly used for most types of epilepsy. Additionally, they often require two or more anti-seizure drugs for seizures to be under control.

It is not completely clear why CBD can reduce some types of seizures. It is known to have a range of biochemical effects on nerve cells in the brain, some of which may have an impact on seizures. Medical research on CBD is still in its early stages.


Prescription CBD is specifically recommended for control of seizures in LGS and Dravet syndrome.

LGS is a developmental disorder that begins in early childhood and is characterized by multiple seizure types, as well as physical and cognitive deficits. The seizures of LGS are difficult to control and are managed with a different medication regimen than that which is used for most epilepsy types.

Dravet syndrome is a developmental disorder that begins in early childhood and is associated with multiple seizure types as well as seizures triggered by fevers. People with Dravet syndrome often have behavioral challenges and learning difficulties.

Even with treatment, people with LGS or Dravet syndrome may continue to experience persistent seizures.

However, studies have shown that CBD, when taken with other anti-seizure medications, reduces the frequency and severity of seizures in people who have these disorders.  

A 2019 review of studies on Epidiolex showed a sustained seizure frequency reduction of between 30 and 63 percent.   Additionally, seizures were about half as severe and the postictal (after seizure) state was less severe as well.

What About Other Seizure Types?

Studies using CBD for seizure control are focused on refractory seizures, which are seizures that are not easily controlled with anti-seizure treatments. It’s still too soon to tell whether it will be beneficial and tolerable for people with other seizure types. As such, CBD is not approved for other types of seizures or epilepsy itself at this time.

Cannabidiol is a controversial treatment because it is one of the components of marijuana, a widely known recreational drug. There are strong opinions about the drug, and proponents advocate for its legalization for medical uses, while some advocate for the legalization of recreational use as well.

At this time, cannabidiol has been proven effective for only a few medical conditions. Due to the side effects, it is recommended to be used with caution.

If you have questions regarding whether cannabidiol is an appropriate treatment for you or someone you know, talk to your healthcare provider first. You can use our Doctor Discussion Guide below to help start that conversation about treatment options and more.

Epilepsy Doctor Discussion Guide

Get our printable guide for your next doctor’s appointment to help you ask the right questions.


Epidiolex comes in an oral solution (liquid form), and the recommended dose is initiated based on weight.

It is generally started at a dose of 2.5 mg/kg twice per day and increased weekly. It can be increased up to a dose of 20 mg/kg per day if needed, but increased side effects have been found to occur at the higher dose.

Anti-seizure medications should be taken at the regularly scheduled times without skipping or combining doses.

Sometimes, children and adults who have LGS or Dravet syndrome have some difficulties taking oral medication due to difficulty swallowing, behavioral problems, and/or cognitive issues. It may be a challenge to get your child to take any medication, and you might need to develop strategies to help with this process.

Side Effects

The side effects of CBD that have been reported in the studies when it was added to other antiseizure medications included:

  • Fever
  • Upper respiratory tract infection/rhinitis
  • Drowsiness
  • Generalized fatigue
  • Sleeping difficulties
  • Weakness
  • Decreased appetite
  • Rashes
  • Diarrhea
  • Vomiting (prolonged seizure requiring emergency attention)
  • Fatigue
  • Lethargy
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In studies, these were more common in the first two weeks on Epidiolex, after which time they tended to diminish. Additionally, many of the studies on the drug involved at least one other anti-seizure drug as well, so the side effects may not all have been due to Epidiolex.

More severe side effects, which you should contact your healthcare provider about right away, include:

  • Symptoms of liver injury:Jaundice (a yellowish color of the skin and eyes), abdominal pain, vomiting, and dark colored urine
  • Mood changes: Depression, anxiety, and suicidal ideation

Myth Buster

CBD itself does not have abuse potential and does not produce the “high” that is typical of marijuana, so you do not need to worry about your child abusing the drug or becoming addicted to it. However, it is possible that others may misunderstand the effects of the drug, particularly because it is new and because it is derived from the same plant that marijuana is derived from.


There’s still much to be learned about how CBD interacts with other anti-seizure drugs.  

It’s possible that CBD may raise the blood level of certain other anticonvulsants such as Topamax and Onfi (clobazam), and may result in side effects.

When used with other anti-seizure drugs, CBD can cause elevated liver enzymes, which is often a sign of liver injury.

In the aforementioned 2019 review of studies on this drug, however, researchers found that while adding Epidiolex to a treatment regimen may increase certain specific side effects, it may actually decrease the overall amount of side effects participants experienced.

Over-the-Counter CBD Products

A multitude of CBD-containing products are on the market, and some people have chosen to use them for seizure control. This trend is likely to grow, especially since the 2018 Farm Bill made hemp-derived products, including CBD, legal at the federal level.  

However, these products aren’t regulated by the FDA and are largely untested. The FDA has warned that CBD products are often mislabeled or overpromise their supposed benefits.  Dosage and quality are likely to be far less consistent with other CBD products, which may put you at risk for more seizures.

In fact, the FDA has issued warnings to many CBD businesses for illegal practices, including those related to the marketing of their products. In some cases, actual CBD content was negligible or less than 1 percent of what the label claimed.

A 2017 study published in JAMA found that 26 percent of products purchased online contained less CBD than their labels claimed.  


Some other CBD products contained other compounds from the marijuana plant, including tetrahydrocannabinol (THC)—the part that gets you “high.”

A Word From Verywell

Given that CBD is a fairly new therapy for epilepsy, you may experience challenges when it comes to health insurance coverage or availability of the medication. If you do, be sure to involve your healthcare provider, who can provide documentation that can help you get an approval for coverage and may be able to refer you to a source that will fill your prescription.

Cannabis Extract in Refractory Epilepsy Study (CERES)

The purpose of this study is to examine whether a low dose of CBD+THC will decrease the frequency of convulsive seizures in adults with drug-resistant epilepsy, when used in addition to standard anti-epileptic drugs (AEDs). This study will also study the genes associated with epilepsy and whether different epileptic syndromes respond to treatment with CBD+THC.

Condition or disease Intervention/treatment Phase
Drug Resistant Epilepsy Drug: Medical Cannabis Drug: Placebo Phase 3

Background: Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two major compounds found in the cannabis plant. Reports from patients, families, and the scientific community suggest that CBD (when used as an add-on therapy) decreases the number of convulsive seizures in children and adults with Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous sclerosis complex.

Trial design: Phase III, double-blind, randomized, placebo-controlled, parallel-group trial, followed by an open phase where treatment allocation will be revealed and all participants will either continue or begin receiving the active study drug.

Participants: Adults (18 years of age and older) with drug-resistant epilepsy, including patients with Dravet and Lennox Gastaut syndromes, and patients with frequent convulsive seizures (e.g., tonic, tonic-clonic, atonic, drop attacks, and focal motor seizures).

Interventions: Capsules containing a ratio of 16 CBD: 1 THC oil at a maximum total daily dose of approximately 300 mg of CBD per day, divided into equal doses in the morning and evening.

Comparator: Placebo capsules containing high-oleic sunflower oil and no active or medicinal ingredients.

Outcomes: Frequency of seizures; side effects; blood levels of AEDs, CBD, THC, and liver enzymes; impact on cognition and quality of life; genetics.

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Sample size: A total of 80 participants (40 assigned to treatment and 40 to control group) recruited from Toronto Western Hospital in Toronto, and University Hospital in London, Ontario.

Time: Each participant will be enrolled for approximately 16 to 18 weeks, while the clinical trial is expected to take place over a period of two years.

Layout table for study information

Study Type : Interventional (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Parallel-Group Study of Cannabidiol Plus Tetrahydrocannabinol (CBD+THC) Given as Adjunctive Therapy in Patients With Refractory Seizures
Actual Study Start Date : January 10, 2019
Actual Primary Completion Date : March 15, 2020
Actual Study Completion Date : March 15, 2020

Capsules containing cannabis extract, dissolved in high-oleic sunflower oil, and CBD/THC in a 16:1 ratio.

The experimental intervention will begin with two weeks of titration (100 mg to 200 mg of CBD per day), followed by four weeks of treatment (maximum 300 mg of CBD per day) and four weeks of maintenance (maximum 300 mg of CBD per day). A two week washout phase will slowly decrease the daily dose (200 mg to 100 mg of CBD per day). All daily doses are equally divided into a morning and evening dose.

Capsules containing a high-oleic sunflower oil, calorie-equated to the active treatment. There will be no active compounds in the placebo treatment.

Following treatment with placebo, all participants in this group will begin treatment with medical cannabis.

The placebo intervention will begin with two weeks of titration, followed by four weeks of treatment. Participants will then be unblinded to their study group and begin two weeks of titration, four weeks of treatment, and two weeks of washout with medical cannabis, following the same dosing and schedule as the experimental group. All daily doses are equally divided into a morning and evening dose.

  1. Frequency of convulsive seizures [ Time Frame: 0 – 10 weeks ]
  1. Number of participants with treatment-related adverse events as assessed by the adverse events questionnaire [ Time Frame: 0- 10 weeks ]
  2. Changes in blood levels of CBD and THC from baseline to end of treatment [ Time Frame: 0 – 10 weeks ]
  3. Changes in blood levels of AEDs from baseline to end of treatment [ Time Frame: 0 – 10 weeks ]
  4. Changes in blood levels of liver enzymes AST, ALT, and GGT from baseline to end of treatment [ Time Frame: 0 – 10 weeks ]
  5. Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life in Epilepsy Inventory (QOLIE-31) questionnaire [ Time Frame: 0 – 10 weeks ]

QOLIE-31 is a 31-item measure assessing health-related quality of life in adults with epilepsy. Seven scales assess seizure worry, overall quality of life, emotional well-being, cognitive and medication effects, and social function.

WHOQOL-BREF is a 26-item measure of physical health, psychological health, social relationships, and environment.

QOLCE is a 55-item scale assessing health-related quality of life in children with epilepsy from the perspective of the parent or caregiver. It covers cognitive, emotional, social, and physical functioning.

GASE is a single-item, 7-point global rating scale that was designed to assess the overall severity of epilepsy.

PSQI is a 19-item measure assessing subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction.

PGIC is a 7-point scale assessing the patient’s perspective of overall improvement and efficacy of treatment. Scores range from “very much improved” to “very much worse”.

CGIC is a 7-point scale assessing the caregiver’s perspective of overall improvement and efficacy of treatment. Scores range from “very much improved” to “very much worse”.

BSI-53 is a 53-item measure assessing psychological profiles. It covers 9 primary domains: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism.

SDS is a 5-item measure assessing functional impairment in three inter-related domains: work/school, social, and family life.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
  • Diagnosis of epilepsy according to the ILAE classification.
  • At least 4 motor seizures per month at the start of the study, despite treatment with at least two different anti-epileptic drugs (given concurrently or sequentially) for at least one year.
  • At least 4 motor seizures per month during the prospective baseline phase (4 weeks) with no 21-day seizure free periods.
  • Stable dose(s) of the same AED(s) for one month prior to screening.
  • Agrees not to take any cannabinoids during the study or any other investigational compound for one month before the study or outside cannabinoids during the study.
  • Is planning to stay in Canada for the duration of the trial.
  • Is able to travel to one of the study sites for in-person visits with the study physicians and to a local lab for blood collection.
  • Has access to telephone, computer, and internet for regular correspondence and to complete the study questionnaires.
  • Participation in a study involving administration of an investigational compound within one month of Visit 1.
  • Evidence of clinically significant non-epileptic disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic, or renal disease, etc.) that in the opinion of the investigators could affect the patient’s safety or trial conduct.
  • Progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
  • Occurrence of psychogenic seizures in the previous year.
  • History of drug misuse/abuse (other than cannabinoids). Consideration may be given to allowing inclusion of subjects with remote history of drug abuse (within a defined relevant time period).
  • Multiple drug allergies (dermatological, hematological, or organ toxicity) or more than one severe drug reaction(s).
  • Pregnancy, breastfeeding.
  • Known or suspected hypersensitivity to cannabinoids, or any of the excipients of the investigational medicinal product.
  • Patients with a history of major depression, suicidal ideation or attempted suicide, schizophrenia or any other psychotic disorder, patients with a family history of schizophrenia.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03808935

Cannabidiol Therapy for Refractory Epilepsy and Seizure Disorders

Cannabis-derived cannabinoids have neuroactive properties. Recently, there has been emerging interest in the use of cannabidiol (CBD)-enriched products for treatment of drug-resistant epilepsy. In 2018, the FDA approved the use of CBD-rich Epidiolex for two severe forms of epilepsy in children (Lennox-Gastaut and Dravet syndromes). Experimental research supports the use of CBD in many CNS disorders, though the mechanisms underlying its anticonvulsant and neuroprotective effects remain unclear. CBD has been shown to reduce inflammation, protect against neuronal loss, normalize neurogenesis, and act as an antioxidant. These actions appear to be due to the multimodal mechanism of action of CBD in the brain. This chapter briefly describes the current information on cannabis pharmacology with an emphasis on the clinical utility of CBD in the treatment of refractory epilepsies and other related seizure conditions. Clinical trials are ongoing for other forms of epilepsy and refractory seizures associated with infantile spasms, tuberous sclerosis, and Rett syndrome. Overall, adjunct CBD has been found to be generally safe and effective for treatment-resistant seizures in children with severe early-onset epilepsy. Whether an add-on CBD is efficacious for the long-term treatment of various epilepsy and seizure types in adults being tested in various clinical trials.

Keywords: CBD, THC; Cannabidiol; Cannabis; Epilepsy; Marijuana; Refractory seizure.

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