A meta-analysis of 550 patients confirmed CBD reduces seizures in Dravet and Lennox-Gastaut syndromes but increases adverse events | Research

The takeaway

A meta-analysis of four randomized controlled trials involving 550 patients found that adjunctive CBD at 10 and 20 mg/kg/day reduced seizure frequency by about 20 percentage points compared to placebo in Dravet and Lennox-Gastaut syndromes, with higher doses causing more treatment withdrawals and adverse events.

Neurologists treating refractory epilepsy; parents of children with Dravet or Lennox-Gastaut syndrome; researchers studying cannabinoid therapeutics.

~20 percentage point seizure reduction vs placebo at both CBD doses

What the researchers found

Researchers pooled data from four randomized, placebo-controlled trials of oral CBD as add-on therapy in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) whose seizures were not controlled by existing medications.

Both CBD dose levels showed similar efficacy: the pooled difference in seizure frequency reduction was 19.5 percentage points (95% CI 8.1-31.0) for 10 mg/kg/day and 19.9 percentage points (95% CI 11.8-28.1) for 20 mg/kg/day compared to placebo.

The higher dose carried more risk: treatment withdrawal risk was 4.20 times higher for 20 mg/kg/day (95% CI 1.82-9.68) versus placebo but not significantly elevated for 10 mg/kg/day (RR 1.45, 95% CI 0.28-7.41).

Adverse events occurred in 87.9% of CBD patients versus 72.2% on placebo (RR 1.22). The most common side effects were somnolence, decreased appetite, diarrhea, and elevated liver enzymes.

Adverse event-related treatment discontinuation was significantly higher with CBD (8.9% vs 1.8%).

Why it matters

This meta-analysis provided key evidence supporting CBD as a treatment for severe childhood epilepsies. The finding that 10 mg/kg/day was similarly effective but safer than 20 mg/kg/day has practical implications for dosing, as it suggests the lower dose may offer a better benefit-risk balance.

The numbers in context

550 patients across 4 trials. Seizure reduction vs placebo: ~20 percentage points for both doses. Adverse events: 87.9% CBD vs 72.2% placebo. Treatment withdrawal RR for 20 mg: 4.20 (p = .001). Treatment withdrawal RR for 10 mg: 1.45 (not significant). Somnolence, decreased appetite, diarrhea, and elevated aminotransferases were the main side effects.

How the study worked

Systematic review and meta-analysis of four randomized, placebo-controlled, blinded trials. 550 patients with LGS or DS. Risk ratios calculated with 95% confidence intervals via inverse variance method.

What this study cannot tell us

Only four trials available, all in LGS and DS specifically. Results may not generalize to other epilepsy types. All trials used pharmaceutical-grade CBD (Epidiolex), so findings do not apply to unregulated CBD products. Short trial durations limit understanding of long-term safety.

How to read the evidence

Strong. Meta-analysis of randomized controlled trials with adequate sample size and consistent findings across doses.

When this study was published

Published in 2018. CBD (as Epidiolex) has since received FDA approval for these indications, with additional post-marketing safety data available.

The bigger picture

This meta-analysis was part of the evidence base that supported FDA approval of Epidiolex (pharmaceutical CBD) for Dravet and Lennox-Gastaut syndromes. It demonstrated that CBD has genuine anti-seizure effects but is not without significant side effects, particularly at higher doses.

Questions still open

Is 10 mg/kg/day the optimal dose for balancing efficacy and safety? Does CBD work in other epilepsy syndromes beyond LGS and DS? What causes the elevated liver enzymes, and is it clinically significant long-term?

Common questions

Can regular CBD oil from a store treat seizures?

This meta-analysis used pharmaceutical-grade CBD (Epidiolex) at precise, high doses (10-20 mg/kg/day). Over-the-counter CBD products vary widely in actual CBD content, purity, and consistency. These findings apply specifically to pharmaceutical CBD, not unregulated products.

Why did nearly 88% of CBD patients have adverse events?

These were patients with severe epilepsy already on multiple medications. The high adverse event rate partly reflects drug interactions and the overall complexity of their treatment. Somnolence and decreased appetite were the most common CBD-specific effects.

Read the original research

Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis.

Drugs, 78(17), 1791-1804

View on PubMed ↗Publisher’s paper ↗

Citation

Lattanzi, Simona; Brigo, Francesco; Trinka, Eugen; Zaccara, Gaetano; Cagnetti, Claudia; Del Giovane, Cinzia; Silvestrini, Mauro. (2018). Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis.. Drugs, 78(17), 1791-1804. https://doi.org/10.1007/s40265-018-0992-5