CBD is generally well-tolerated with mild side effects like sleepiness and diarrhea, but can cause severe, life-threatening reactions when combined with valproate or clobazam, two drugs commonly used in the epilepsy patients who take CBD.
Epilepsy patients taking CBD, neurologists, and parents of children on multiple seizure medications.
Life-threatening reactions possible with valproate or clobazam
What the researchers found
Short-term CBD side effects are generally transitory, dose-dependent, and mild to moderate: somnolence, decreased appetite, and diarrhea. However, severe life-threatening reactions can occur, often related to uncontrolled combinations with valproate (hepatotoxicity risk) or clobazam (excessive sedation). These are widely used in Dravet and Lennox-Gastaut patients who are the target population for CBD.
Why it matters
The very patients most likely to benefit from CBD (those with severe epilepsy) are also taking the drugs most likely to cause dangerous interactions with CBD, making monitoring essential.
The numbers in context
No specific incidence rates. Review noted dose-dependent effects and identified valproate and clobazam as primary interaction risks.
How the study worked
Brief review summarizing available data on short-term adverse events from clinical trials that led to Epidiolex FDA approval.
What this study cannot tell us
Brief review focused on short-term effects. Long-term safety data are lacking. Based primarily on clinical trial populations.
How to read the evidence
Based on clinical trial data from FDA approval process, the strongest available evidence.
When this study was published
2020 review.
The bigger picture
The interaction concern highlights a broader issue: CBD is often perceived as universally safe because it is "natural," but it has real pharmacological interactions that can be serious.
Questions still open
- What is the long-term safety profile of CBD in children? Can dosing adjustments of valproate and clobazam eliminate the interaction risk?
Common questions
Is CBD safe?
What are the side effects of CBD?
Read the original research
Adverse effects of cannabinoids.
Epileptic disorders : international epilepsy journal with videotape, 22(S1), 29-32
Citation
Anciones, Carla; Gil-Nagel, Antonio. (2020). Adverse effects of cannabinoids.. Epileptic disorders : international epilepsy journal with videotape, 22(S1), 29-32. https://doi.org/10.1684/epd.2019.1125
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