CBD Significantly Reduces Seizures in Tuberous Sclerosis: Major Trial
What Researchers Found About Epilepsy and Cannabis
The Study at a Glance
Published
JAMA Neurology, 2021
Researchers
Multiple international centers (International)
Study Type
Randomized Controlled TrialParticipants
224 patients · 16 weeks
Key Finding
Cannabidiol significantly reduced TSC-associated seizures compared with placebo. The 25-mg/kg/day dosage had a better safety profile than the 50-mg/kg/day dosage.
Key Finding: Cannabidiol significantly reduced TSC-associated seizures compared with placebo. The 25-mg/kg/day dosage had a better safety profile than the 50-mg/kg/day dosage.
What Researchers Studied About Epilepsy and Cannabis
Tuberous sclerosis complex (TSC) is a genetic condition that causes tumors to grow in various organs and is associated with medication-resistant epilepsy. CBD has been shown to help seizures in other epilepsy syndromes, but had not been studied specifically in TSC.
This was a double-blind, placebo-controlled randomized clinical trial (GWPCARE6) conducted at 46 sites in Australia, Poland, Spain, Netherlands, UK, and US.
The study evaluated whether cannabidiol (CBD) could reduce seizures associated with TSC in patients aged 1-65 years who had at least 8 TSC-associated seizures during baseline.
How This Randomized Controlled Trial Was Conducted
Of 255 patients screened, 224 were randomized into three groups: - CBD 25 mg/kg/day: 75 patients - CBD 50 mg/kg/day: 73 patients - Placebo: 76 patients
All patients were already taking at least one antiepileptic medication. Treatment lasted 16 weeks. The primary outcome was the percentage change in TSC-associated seizure frequency compared to the 4-week baseline period.
A total of 201 patients completed treatment.
Epilepsy Treatment Results
The Main Results:
- 1CBD 25mg: 48.6% reduction in seizures (95% CI 40.4%-55.8%)
- 2CBD 50mg: 47.5% reduction in seizures (95% CI 39.0%-54.8%)
- 3Placebo: 26.5% reduction in seizures (95% CI 14.9%-36.5%)
- 4CBD 25mg vs placebo: 30.1% additional reduction (P < .001)
- 5CBD 50mg vs placebo: 28.5% additional reduction (P = .002)
- 6Both doses equally effective, but 25mg had better safety profile
- 7Elevated liver enzymes: 18.9% of CBD patients vs 0% placebo (mostly in patients also on valproate)
By the Numbers
| Statistic | What It Means |
|---|---|
| 224 patients | Randomized in this trial across 46 international sites (ages 1-65 years) |
| 48.6% | Seizure reduction with CBD 25mg/kg/day (vs 26.5% with placebo) |
| 30.1% | Additional seizure reduction with CBD 25mg vs placebo (P < .001) |
| 18.9% | Of CBD patients had elevated liver enzymes (vs 0% placebo) |
Randomized in this trial across 46 international sites (ages 1-65 years)
Seizure reduction with CBD 25mg/kg/day (vs 26.5% with placebo)
Additional seizure reduction with CBD 25mg vs placebo (P < .001)
Of CBD patients had elevated liver enzymes (vs 0% placebo)
What This Means for Epilepsy Patients
If you or your child has tuberous sclerosis complex with drug-resistant seizures, this trial provides strong evidence that cannabidiol (CBD) can help.
Both CBD doses (25mg and 50mg per kg/day) reduced seizures by nearly 50%, which was significantly better than placebo. The lower dose (25mg/kg/day) is preferred because it was equally effective but had fewer side effects.
Common side effects include diarrhea (31% at lower dose, 56% at higher dose) and sleepiness (13% at lower dose, 26% at higher dose).
Important: About 19% of patients on CBD had elevated liver enzymes, especially those also taking valproate. Liver monitoring is essential during CBD treatment.
This research led to FDA approval of Epidiolex for TSC-associated seizures.
Quick Answers: Epilepsy and Cannabis
Direct answers based on the findings of this study:
Research Summary: Answers are based on published peer-reviewed studies and represent research findings, not medical recommendations. Individual results may vary. Always consult a healthcare provider before making treatment decisions.
Does Epidiolex work for tuberous sclerosis seizures?
Yes. A JAMA Neurology trial of 224 patients found CBD (Epidiolex) at 25mg/kg/day reduced seizures by 48.6% compared to 26.5% with placebo (P < .001). Both CBD doses tested were significantly effective.
Source: Thiele et al., JAMA Neurology, 2021 (PMID: 33346789)
What is the best CBD dose for TSC seizures?
25mg/kg/day is preferred. The JAMA trial found both doses were equally effective (48.6% vs 47.5% seizure reduction), but the lower dose had a better safety profile with fewer side effects.
Source: Thiele et al., JAMA Neurology, 2021 (PMID: 33346789)
Is CBD safe for people with tuberous sclerosis?
CBD was generally well-tolerated but has risks. In the JAMA trial, 18.9% of CBD patients had elevated liver enzymes (vs 0% placebo), especially those also on valproate. Liver monitoring is essential during treatment.
Source: Thiele et al., JAMA Neurology, 2021 (PMID: 33346789)
This is educational content, not medical advice
The research summarized here is for informational purposes only. Individual results may vary, and what works in studies may not work the same way for everyone. Always consult with a qualified healthcare provider before making changes to your treatment plan or starting medical cannabis therapy.
Important Limitations
This study has some caveats to keep in mind when interpreting the results:
- Trial duration was 16 weeks, long-term effects unknown
- All patients were on other antiepileptic medications
- Elevated liver enzymes occurred in 18.9% of CBD patients
- Higher discontinuation rate in CBD groups (8-10 patients) vs placebo (2 patients)
- Liver enzyme elevations more common in patients on valproate
The Bottom Line on Cannabis for Epilepsy
This major JAMA Neurology trial provides strong evidence that cannabidiol reduces seizures in tuberous sclerosis complex. CBD 25mg/kg/day reduced seizures by 48.6% vs 26.5% with placebo (P < .001). The lower dose is recommended due to fewer side effects. Liver monitoring is essential as 18.9% of patients had elevated liver enzymes. This research supports the FDA approval of CBD (Epidiolex) for TSC-associated seizures.
Do You Qualify for Medical Marijuana?
If you're living with Epilepsy, you may qualify for a medical marijuana card. Our licensed physicians can evaluate you from home via telehealth.
Related Research & Resources
Related Research
Condition Research
Get Your Card
This condition qualifies for medical marijuana in:
Source
Thiele EA, Bebin EM, Bhathal H, et al. "Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial" JAMA Neurology. 2021. DOI: 10.1001/jamaneurol.2020.4607
Important Information
Not Medical Advice: This research summary is for educational purposes only. It should not be used to diagnose, treat, cure, or prevent any disease or medical condition. Always consult a qualified healthcare provider before starting or changing any treatment.
Individual Variation: Research findings represent group averages. Your individual response to cannabis may differ based on genetics, other medications, underlying conditions, and many other factors.
Last reviewed: January 25, 2026
Important Notices
Research Summary Disclaimer
This content represents our interpretation of published scientific research for educational purposes. It should not be used to make treatment decisions without consulting a qualified healthcare provider. Individual results may vary from study findings.
FDA Notice
These statements have not been evaluated by the FDA. Cannabis is not intended to diagnose, treat, cure, or prevent any disease. The FDA has not approved cannabis for any medical condition except specific prescription medications.
Copyright & Fair Use
Research summaries are provided under fair use (17 U.S.C. § 107) for educational purposes. We provide brief summaries with attribution, not full reproductions. All studies remain the intellectual property of their respective authors and publishers.
Data Sources
Study information sourced from PubMed®, U.S. National Library of Medicine. Inclusion does not imply endorsement by NLM, NIH, or the federal government.
For complete information, see our Terms of Use and Research Content Policy.
FAQs: Cannabis for Epilepsy
Does CBD help seizures in tuberous sclerosis?
Yes. A JAMA Neurology trial of 224 patients found CBD 25mg/kg/day reduced seizures by 48.6% vs 26.5% with placebo (P < .001). This led to FDA approval of Epidiolex for TSC-associated seizures.
What dose of CBD is best for TSC seizures?
25mg/kg/day is recommended. The trial found 25mg/kg/day and 50mg/kg/day were equally effective (48.6% vs 47.5% seizure reduction), but the lower dose had fewer side effects.
What are the side effects of CBD for TSC?
Common side effects include diarrhea (31% at 25mg dose) and somnolence/sleepiness (13% at 25mg dose). Elevated liver enzymes occurred in 18.9% of CBD patients, especially those also taking valproate. Liver monitoring is essential.