Current Series: Aes 2018 Highlights

Trevor Resnick, MD: Cannabidiol is a derivative of cannabis, and we don’t really know the mechanism of action of cannabidiol. It may be linked to the G-receptor protein. We don’t know. Nevertheless, it has been demonstrated to be effective in patients with Lennox-Gastaut syndrome and in patients with Dravet syndrome. And it’s actually approved for seizures associated with those 2 syndromes. And I think it’s approved above 2 years of age. And the effectiveness of cannabidiol was gratifying in those 2 syndromes, and it’s approved for those 2 syndromes.

It does cause [adverse] effects, and the major [adverse] effects are fatigue, sleepiness, [and] diarrhea. And another, not specifically [an adverse] effect, but it does have interaction with some medications that are commonly used for both those syndromes.

There was a study looking at tolerance with cannabidiol in those 2 syndromes. And they defined tolerance as 30% of the patients needing a change in their dose. And based upon that definition and a mean dose of 12 mg/kg, they found that tolerance did exist in a significant number of the patients in that study. Interestingly, in the other study that we were discussing earlier relating to the approval of cannabidiol in Dravet syndrome and Lennox-Gastaut syndrome, there was an open-label extension looking at how those patients in the study did if they were maintained on cannabidiol subsequent to the study.

And in that study, there was no demonstrated tolerance. And I think the reason for that, and there may be other reasons as well, but I think the reason for that is that the mean dose in the open-label extension for cannabidiol was 20-something, 23 mg/kg, whereas the mean dose in the study that demonstrated tolerance was 12 mg/kg. So because it was a lower dose, there was a greater likelihood that there would be a need to increase the dose. And in fact, in that tolerance study, when they did increase the dose, about 50% of the patients did well. So I think it was more an issue of dosing rather than true tolerance.