While there is extensive personal experience, to this day there are still no controlled, randomized clinical trials testing CBD in this age group.
The two age groups most affected by epilepsy are the elderly and children under five. Last time we focused on the former, finding a paucity of clinical evidence supporting the use of cannabidiol (CBD) in the treatment of adult epilepsy. Now we turn to the evidence for its use in paediatric epilepsy.
To this day there are no controlled randomized clinical trials testing CBD in this age group. All evidence comes from single case reports, clinical surveys, retrospective studies and uncontrolled open-label trials.
Charlotte is undoubtedly the best-known case study. This five-year-old girl affected by an intractable type of epilepsy – Dravet syndrome – was suffering from 300 seizures weekly, before she was given a cannabis extract rich in CBD. Her symptoms diminished drastically, and 20 months later she was only experiencing three seizure per month.
Another interesting case was reported by Drs. Dimah Saad and Charuta Joshi of the University of Iowa Children’s Hospital. A ten-month-old boy diagnosed with malignant migrating partial seizures, resistant to antiepileptic drugs, was proposed to a full CBD trial. Six months later, he had gone down from 10 to 20 seizures daily to five a week. He continued to receive 80 mg of CBD daily together with his previous antiepileptic drugs.
In 2013, Brenda Porter and Catherine Jacobson of Stanford University conducted an online survey on 19 parents of children with intractable epilepsy who had been using artisanal CBD preparations to manage their kids’ seizures. Sixteen parents affirmed that the treatment had significantly reduced the frequency of seizures; with two reporting a complete stop and eight mentioning an 80% reduction. Side effects included drowsiness and fatigue.
In 2015, a larger survey was conducted with 117 parents of epileptic children who had been treated with CBD for a median period of 7 months. Overall, 85% of the parents reported a significant reduction in seizure frequency, with 14% reporting a complete halt. Other symptoms also improved, and the only common side effect was an increase in food consumption. Contrary to the norm, five parents reported an aggravation of their kids’ condition following CBD administration.
The first uncontrolled open-label trial with CBD was performed in Italy, and included 16 children with resistant forms of epilepsy. Of these, four had a reduction in the frequency and intensity of seizures, as well as an improvement in other symptoms. Nine other patients dropped from the trial because of monetary costs. No side effects were detected. However, this study was never formally published and only the abstract can be found.
In 2015, another uncontrolled open-label trial was conducted. It included 162 children and young adults, from ages 1 to 30, with refractory epilepsy, pertaining to several health centres. The patients were given a 99% pure CBD oil to be administered on top of the current antiepileptic treatment. Parents and caregivers were asked to keep a diary where they registered seizure occurrences and adverse events, for a minimum of 12 weeks.
Most patients tolerated the treatment, despite a 25% prevalence of mild to moderate side effects that included somnolence, decreased appetite, diarrhea, fatigue and convulsions. Regarding seizures, there was a 36.5% median reduction.
Although the evidence here reviewed seems promising, caution is warranted for several reasons. First of all, parental reports are at an abnormal risk of bias and placebo effects. A team working at the University of Colorado showed that parents of children who had moved into the state to seek cannabis treatment reported a seizure reduction that was twice as high as the one reported by the parents of children who already lived in the state. Furthermore, when EEG data was analyzed, no association was found between that and the improvements reported by the parents.
Another factor that could confound the conclusions of these studies is drug interactions. CBD strongly inhibits hepatic enzymes and has been shown to increase by 500% the concentrations of other antiepileptic drugs administered concomitantly. This phenomena might lead to an overestimating of the efficacy of CBD in relation to other drugs. In fact, in the 2015 clinical trial, those patients receiving clobazam were four times more likely to have a 50% reduction in seizures than those not receiving it. This reinforces the idea that in the absence of well-designed control groups, it is almost impossible to ascertain the exact impacts of CBD treatment.
A third concern is raised by the short period of monitoring in these studies. Long-term use of marijuana has been associated with altered brain development, cognitive impairment, poor educational outcome, and with a drastic increase in violent behaviour. Whether or not CBD shares some of these effects remains to be seen.
As with adult epilepsy, we will have to wait for longer controlled clinical trials to be concluded, before we can judge the efficacy and safety of CBD in the treatment of paediatric epilepsy.
GW Pharmaceuticals in March announced results of a Phase 3 trial of Epidiolex (cannabidiol or CBD) in the treatment of Dravet Syndrome, a rare and severe form of epilepsy in children and for which there are no FDA-approved treatments. The Phase 3 study randomized, placebo controlled trial showed patients taking Epidiolex achieved a median reduction in monthly convulsive seizures of 39 percent compared with a reduction on placebo of 13 percent, which was highly statistically significant (p=0.01).