CBD Serious Side Effects: What the Clinical Trials Show
What Researchers Found About Epilepsy and Cannabis
The Study at a Glance
Published
Expert Opinion on Drug Metabolism and Toxicology, 2020
Researchers
Multiple institutions (Brazil)
Study Type
Systematic ReviewDuration
N/A (review of RCTs)
Key Finding
Serious adverse effects related to CBD in RCTs are rare and include mainly elevated transaminases, convulsion, sedation, lethargy, and upper respiratory tract infections. These are related to drug-drug interactions with valproate and clobazam.
Key Finding: Serious adverse effects related to CBD in RCTs are rare and include mainly elevated transaminases, convulsion, sedation, lethargy, and upper respiratory tract infections. These are related to drug-drug interactions with valproate and clobazam.
What Researchers Studied About Epilepsy and Cannabis
This review analyzed serious adverse effects (SAEs) of cannabidiol (CBD) and their possible relation to drug-drug interactions.
The focus was on SAEs reported in randomized controlled trials involving oral CBD administered for at least 1 week.
Both healthy volunteers and clinical samples were included.
How This Systematic Review Was Conducted
Researchers systematically analyzed serious adverse effects reported in RCTs of oral CBD.
Inclusion criteria: RCTs with oral CBD for at least 1 week in healthy volunteers or clinical populations.
The relationship between SAEs and concurrent medications was examined.
Epilepsy Treatment Results
The Main Results:
- 1Most acute and prolonged adverse effects of CBD are MILD TO MODERATE
- 2Serious adverse effects (SAEs) are RARE
- 3Main SAEs: elevated transaminases (liver enzymes)
- 4Main SAEs: convulsion
- 5Main SAEs: sedation and lethargy
- 6Main SAEs: upper respiratory tract infections
- 7Elevated transaminases related to CONCOMITANT VALPROATE use
- 8Sedation, lethargy, and respiratory infections related to CONCOMITANT CLOBAZAM use
- 9Epileptic patients should be monitored for drug-drug interactions
By the Numbers
| Statistic | What It Means |
|---|---|
| Rare | Serious adverse effects from CBD are uncommon |
| Mild-moderate | Most CBD adverse effects are not serious |
| Valproate | Drug causing elevated liver enzymes when combined with CBD |
| Clobazam | Drug causing sedation and respiratory infections when combined with CBD |
Serious adverse effects from CBD are uncommon
Most CBD adverse effects are not serious
Drug causing elevated liver enzymes when combined with CBD
Drug causing sedation and respiratory infections when combined with CBD
What This Means for Epilepsy Patients
This safety review has reassuring and cautionary news about CBD.
The reassuring news: Most CBD side effects are mild to moderate, and serious adverse effects are RARE.
The cautionary news: Serious side effects DO occur, and they are linked to specific drug interactions.
If you take VALPROATE (Depakote, an epilepsy/mood medication): - CBD + valproate can cause elevated liver enzymes (hepatotoxicity) - Your liver function should be monitored
If you take CLOBAZAM (Onfi, an epilepsy medication): - CBD + clobazam can cause sedation, lethargy, and upper respiratory infections - These effects are due to drug-drug interactions
For epilepsy patients: You should be monitored when using CBD with antiepileptic drugs due to possible interactions.
Key takeaway: CBD is generally well-tolerated, but drug interactions can cause serious problems. Tell your doctor about all medications you take.
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.
What are the serious side effects of CBD?
Serious CBD adverse effects are rare and include: elevated liver enzymes (mainly with valproate), convulsion, sedation, lethargy, and upper respiratory infections (mainly with clobazam). Most CBD side effects are mild to moderate.
Source: Dos Santos et al., Expert Opin Drug Metab Toxicol, 2020 (PMID: 32271618)
Can I take CBD with my epilepsy medication?
Caution is needed. CBD with valproate can cause elevated liver enzymes. CBD with clobazam can cause sedation and respiratory infections. Epileptic patients should be monitored for drug-drug interactions.
Source: Dos Santos et al., Expert Opin Drug Metab Toxicol, 2020 (PMID: 32271618)
Does CBD hurt your liver?
CBD can elevate liver enzymes, but this is mainly seen when CBD is taken with valproate (Depakote). This drug-drug interaction is the primary cause of CBD-related hepatotoxicity in clinical trials.
Source: Dos Santos et al., Expert Opin Drug Metab Toxicol, 2020 (PMID: 32271618)
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:
- Review of existing RCTs only
- Focused on oral CBD (at least 1 week)
- Drug interactions may not apply to all CBD formulations
- Long-term safety data still limited
- Over-the-counter CBD products may differ from pharmaceutical CBD
The Bottom Line on Cannabis for Epilepsy
This review of RCTs found CBD serious adverse effects are RARE. Most side effects are mild-moderate. However, drug interactions cause important SAEs: elevated liver enzymes with valproate, and sedation/respiratory infections with clobazam. Epilepsy patients on CBD should be monitored for drug-drug interactions.
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
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Source
Dos Santos RG, Guimaraes FS, Crippa JAS, et al. "Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials" Expert Opinion on Drug Metabolism and Toxicology. 2020. DOI: 10.1080/17425255.2020.1754793
Important Information
Study Age: This study was published 6 years ago. Newer research may have updated or refined these findings.
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
Is CBD safe?
Generally yes. A review of RCTs found most CBD adverse effects are mild to moderate, and serious adverse effects are rare. However, drug interactions can cause problems with valproate and clobazam.
Does CBD cause liver damage?
CBD can cause elevated liver enzymes (transaminases), but this is primarily seen when CBD is taken WITH valproate (Depakote). Patients on both medications should have liver function monitored.
What drugs interact with CBD?
Valproate: causes elevated liver enzymes when combined with CBD. Clobazam: causes sedation, lethargy, and upper respiratory infections when combined with CBD. Other antiepileptic drugs may also interact.