Preliminary findings from an University of Saskatchewan led clinical trial demonstrate reductions in seizure frequency in children with drug-resistant epilepsy with daily use of a 1:20 tetrahydrocannabinol (THC):cannabidiol (CBD) cannabis extract product.
This open label dose-escalation trial led by two pediatric neurologists, Dr. Richard Huntsman and Dr. Richard Tang-wai, was published in Frontiers in Neurology. In this dose-escalation trial, children with drug-resistant epilepsy aged 1 – 10 years were given twice daily oral doses of the 1:20 THC:CBD cannabis herbal extract beginning at CBD equivalents of 2 mg/kg body weight/per day, and increasing the dose each month to 5 – 6 mg/kg/day, then 8 – 9 mg/kg/day and finally 10 – 12 mg/kg/day followed by a one month tapering off of the cannabis herbal extract. Preliminary results from 7 participating children indicate that all 7 children responded to the 1:20 cannabis product. All children showed a reduction in average daily seizure frequency at a CBD equivalent dose of 5 -6 mg/kg/day. By the 10 – 12 mg/kg/day dose, an average 74% reduction in seizure frequency was observed, while 3 children became seizure free. At the end of the trial with a one-month weaning off period, children still continued to show reductions in seizure frequency. Interestingly, the dose required for improvements in seizure frequency with the 1:20 THC:CBD Cannabis oil product were lower than doses reported for pure CBD products.
Health care providers have been concerned about the THC content of cannabis products and the risk of intoxication. In this study, none of the children showed symptoms of intoxication. Furthermore, 1:20 cannabis product was well-tolerated and no serious adverse effects were observed. Side effects were noted only when children were taking clobazam and reductions in the clobazam dose resolved the observed side effects.
In addition to reductions in seizure frequency, all participating children showed improvements in quality of life scores, in particular cognitive, social, and emotional functioning subscales. The study included measurements of the minimum steady state plasma concentrations of CBD, THC, and another cannabinoid, cannabichromene, which composed 4% of the 1:20 cannabis product used in the trial. As dose increased, the minimum steady state plasma concentrations of all measured cannabinoids increased proportionally with dose suggesting linear pharmacokinetics. Seizure control and quality of life scores also tended to increase with increasing dose. In children who were seizure free on the 1:20 THC:CBD cannabis herbal extract, the minimum steady state plasma concentrations of CBD ranged from 54.8 -78.9 ng/mL, concentrations much lower than CBD plasma concentrations required for seizure reduction with pure CBD products. THC plasma concentrations remained less than 4.6 ng/mL even at the highest dose. Except for clobazam, the steady state plasma concentrations of other anticonvulsant medications were unchanged with increasing doses of the 1:20 cannabis product.
The preliminary findings are promising. A 1:20 THC:CBD cannabis herbal extract might be a possible treatment for children with epilepsy who fail traditional anticonvulsant medications. However, the study findings must be interpreted with caution. The data only represent 7 children of a total of 20 children recruited for the study, which was funded by the Jim Pattison Children’s Hospital Foundation, the Saskatchewan Health Research Foundation, the Durwood Seafoot Estate, and the Savoy Foundation. More robust evidence to support the use of a 1:20 THC:CBD cannabis herbal extract in drug-resistant epilepsy must follow from a rigorously designed randomized, placebo-controlled clinical trial. The study team is completing the current trial and planning a larger international clinical trial in children with drug-resistant epilepsy.