Cannabidiol can be “cautiously construed” as a moderately effective and appropriate treatment for children with severe epilepsy, according to two of Australia’s leading experts in the field.
However, cannabidiol (CBD) – which due to its comparative lack of psychotropic effects has become the most researched compound found in the Cannabis sativa plant – should be considered a third-line agent due to lack of long-term data, the existence of 25 established antiepileptic medications and the high cost of production.
“Cannabidiol is a medicine, not a miracle and should be managed as such … It is hoped that further investigation in class 1 trials and high level research is encouraged and continues, otherwise we may return to the days of snake oil,” conclude Dr John Lawson, paediatric neurologist at Sydney Children’s Hospital and Professor Ingrid Scheffer, paediatric neurologist and professor at the University of Melbourne, in a review article published in the British Journal of Pharmacology.
They find the best evidence for short-term efficacy and adverse events is contained in three recently published double-blind randomised controlled trials of the cannabidiol (CBD) extract formulation Epidiolex: a trial of 120 children (aged 2-18) with Dravet syndrome, and two trials involving 171 and 225 patients (age range 2-55) with Lennox-Gastaut syndrome, which showed significant median seizure frequency reductions of 17% to 23% respectively compared to placebo.
However they acknowledge that critics say the efficacy seen in the trials may be partly related to drug interactions such as with clobazam and that this secondary endpoint data had not been published.
“The implication here is that the CBD is merely increasing the available clobazam and its metabolites to achieve its anti-epileptic effect; an issue that still remains to be resolved,” they write.
The authors also note the long-term safety has not been established for cannabidiol, which they says was a mainstay in epilepsy treatment until the development of phenobarbital (1912) and phenytoin (1937).
The relevance of the well-known adverse health effects associated with recreational use of marijuana, such as psychosis, to pure CBD products “is very uncertain”, they add.
“A particular worry is the effect on children as little is known about the potential adverse side effects of CBD on brain development and behaviour,” they write, noting while there is little scientific evidence in this area, an animal study has shown CBD produces behavioural abnormalities in offspring, and other research found prenatal exposure in humans leads to higher rates of anxiety and depression in teens.