Long-term CBD for childhood epilepsy: 27% sustained response, but 81% had adverse events | Research

The takeaway

Over a four-year period, CBD was effective in 27% of children with refractory epilepsy (three became seizure-free), but 81% experienced adverse events and only 35% remained on treatment at two years.

Parents of children with epilepsy, pediatric neurologists, and researchers studying long-term CBD outcomes.

11.5% became seizure-free, but 57.7% stopped for lack of efficacy

What the researchers found

Seven of 26 children (26.9%) achieved sustained >50% seizure reduction, including 3 (11.5%) who became seizure-free. However, 80.8% had adverse events (appetite loss 38%, diarrhea 35%, weight loss 31%), 23.1% had serious adverse events (status epilepticus, catatonia, hypoalbuminemia), and 15 (57.7%) discontinued for lack of efficacy. Retention declined rapidly in the first 6 months.

Why it matters

This is one of the longest follow-up studies of CBD for childhood epilepsy. While the responders had dramatic results (including seizure freedom), the high adverse event and discontinuation rates give a realistic picture of long-term use.

The numbers in context

26 children enrolled. Mean age 9.3 years. Mean CBD exposure 21 months. 26.9% sustained >50% seizure reduction. 11.5% seizure-free. 80.8% adverse events. 23.1% serious adverse events. 57.7% discontinued for lack of efficacy. 34.6% retained at 24 months.

How the study worked

Open-label prospective study through expanded access programs (April 2013-December 2014). 26 children aged 1-17 with refractory epilepsy received CBD as add-on therapy at 5-25 mg/kg/day. Mean treatment duration was 21 months (range 4-53 months).

What this study cannot tell us

Open-label study with no placebo group. Small sample size. Artisanal CBD formulation, not pharmaceutical-grade. All patients on concurrent antiepileptic drugs making it hard to isolate CBD effects.

How to read the evidence

Moderate: prospective open-label study with long follow-up (up to 53 months), but small sample and no control group.

When this study was published

Published in 2019.

The bigger picture

The reality of CBD for severe epilepsy is more nuanced than headlines suggest. For the minority who respond, the benefits can be life-changing. But the majority of patients in this study saw no benefit and many experienced significant side effects.

Questions still open

Can we predict which children will respond to CBD? Would pharmaceutical-grade CBD produce different retention rates? Are the serious adverse events (catatonia, status epilepticus) caused by CBD or the underlying epilepsy?

Common questions

Is a 27% response rate good for epilepsy?

For refractory epilepsy (these children had failed an average of 7 prior medications), any new treatment that helps over a quarter of patients is clinically meaningful. But it also means 73% did not benefit.

Why did so many children have side effects?

CBD was added on top of existing antiepileptic drugs, and interactions between CBD and these medications likely contributed to adverse events like appetite loss and liver enzyme changes.

Read the original research

Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US.

CNS drugs, 33(1), 47-60

View on PubMed ↗Publisher’s paper ↗

Citation

Sands, Tristan T; Rahdari, Shahryar; Oldham, Michael S; Caminha Nunes, Eduardo; Tilton, Nicole; Cilio, Maria Roberta. (2019). Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US.. CNS drugs, 33(1), 47-60. https://doi.org/10.1007/s40263-018-0589-2