David Casarett MD

 

The problem:  There are several syndromes of epilepsy in children that can be very difficult to treat.  They may have dozens or even hundreds of seizures a day, with devastating effects on their quality of life, development and survival.

 

Why do this study?  There is growing interest cannabis and pediatric epilepsy, and there have been several clinical trials. But most of these trials have been small, of varying quality, and sometimes without a control group.  Looking at each of these studies in isolation, it’s difficult to tell whether cannabis is effective.  So this study was designed to collect all of the research that’s been done into one analysis.

 

The study: The authors pooled 4 randomized controlled trials and 17 non-randomized studies through April of 2018.  Most were studies of CBD or contained CBD.  The main outcome the authors looked at was children who were seizure-free.  Among the controlled trials, CBD didn’t increase the likelihood that children would be seizure-free (1 trial). Nor did it improve quality of life (3 trials), sleep (3 trials), or vomiting (4 trials).  However, CBD was associated with a reduced seizure frequency (3 trials), and an increase in the number of patients with at least a 50% reduction in seizures (1 trial).  Results from the non-randomized studies were generally consistent with the results of the randomized controlled trials.

 

Conclusions:  The authors conclude that CBD is probably effective for pediatric seizures.

 

What does this study add?  This study is helpful because it gives some perspective on more than 20 studies with different designs and variable quality.  Overall, there seems to be growing evidence that CBD is effective in managing intractable pediatric epilepsy.

 

Funder: None

 

Author conflicts: One author is employed by a licensed cannabis producer

 

Commentary:

This is a careful review of multiple very different studies.  The authors did a good job of identifying and analyzing outcomes that the studies had in common.  Nevertheless, there are a couple of cautions to keep in mind.  First, all 4 of the controlled trials included here, and about half of the uncontrolled trials, are of one proprietary CBD product (Epidiolex). So we should be cautious in generalizing these results to all CBD formulations. 

Second, the vast majority of the trials included in this study didn’t compare CBD to a control group (e.g. a placebo).  These sorts of uncontrolled studies tend to overestimate the effectiveness of drugs.  Although in this study, the results of the controlled trials and uncontrolled studies generally pointed in the same direction, uncontrolled studies may overestimate benefits.

Finally, there’s one other fact about this study—and CBD in general—that’s worth noting.  Many children in these trials were taking the antiepileptic drug clobazam.  That's important because CBD inhibits the enzyme that metabolizes clobazam, increasing its levels.  So even if CBD is beneficial it's possible that CBD also increases the blood levels of clobazam, making it more effective.