Conference Coverage
But none of the AEDs showed a consistent pattern of change in levels with the addition of CBD. “Many patients experienced decreases; some experienced increases. But especially for the most common drugs, we found that the ranges were pretty wide,” he said.
Data from five patients showed an average threefold increase in the level of the active metabolite of clobazam, N-desmethylclobazam, without any change in levels of the drug itself, suggesting that the CBD was interfering with clearance of the metabolite.
The findings are not definitive, given that the patients were on multiple medications that can influence levels of each other, stressed Dr. Friedman, who disclosed no relevant conflicts of interest.
“Until formal drug-drug interaction studies are done, we refrain from any specific advice, except for, make sure if your patients are on CBD, whether they are getting it through artisanal preparations or as part of a compassionate use study, that background AEDs are monitored, and if they are on clobazam, make sure to check the N-desmethyl metabolite level as well,” he recommended.
Expectations may influence perceived benefit
Dr. Kevin E. Chapman, associate professor at Children’s Hospital Colorado, Aurora, and his colleagues retrospectively reviewed data of 75 patients who reported using oral cannabis extract.
Dr. Kevin E. Chapman
In Colorado, cannabis is legal for both medical and recreational use. However, patients must become residents, obtain a prescription from two specialized physicians, get a medical marijuana ID card (“red card”), and purchase the product from a dispensary, paying out of pocket, as it is not yet covered by insurance.
“We have had a fairly large influx of patients from out of state ever since medical marijuana became legal in our state,” Dr. Chapman noted in a press briefing. However, neurologists are often reluctant to raise the topic with patients “because of the concerns about the fact that it’s still illegal at the federal level. We worry about our own personal DEA licenses if we were to prescribe the medication.”
But when they learn patients are starting CBD therapy, “our practice is to encourage families not to make dramatic changes to seizure medications because for us, then it becomes hard to know how many of the problems that they have are from the CBD or how much of the benefit is from the CBD.”
On average, patients used their extract for 5.6 months. Overall, 33% had a response, defined as a decrease of more than half in seizure frequency as reported by parents (a rate similar to that seen with placebo). The rate was 0% among those with Doose syndrome, 25% among those with Dravet syndrome, and 89% among those with Lennox-Gastaut syndrome.
But analyses identified only a single predictor of response: moving to the state to obtain the extract. “I think it’s understandable that families have high hopes when they move to Colorado that it’s going to be effective … I don’t know if there is a bit of bias by families really wanting for it to work and that’s part of the reason we saw that,” said Dr. Chapman, who disclosed no relevant conflicts of interest.
A total of 10% of patients who had electroencephalograms (EEGs) both before and after starting extract had improvements in their interictal EEGs. However, none of them were among the group who had a response.
Use of extract was associated with some other benefits: Thirty-three percent of patients reported better alertness and/or behavior, 11% reported better language and motor skills, and 7% reported better sleep.
The most common adverse event was a worsening of seizures, seen in 13% of children, followed by somnolence, seen in 12%, and gastrointestinal symptoms, seen in 11%.
“What our study really sort of shows for us was that we really need a better study, something a little bit more controlled, because there are a lot of different strains that are being used out there, and we were not able to tease out what strain of cannabis worked best in our patient population. People are using CBD strains, THC strains, a combination of things, whereas I think we really need more of a uniform strain or preparation, and then more of a placebo-controlled trial,” Dr. Chapman said.
“At this point I think it’s a bit early to be selling the farm, so to speak, and moving to Colorado,” he concluded. “Right now there’s quite a bit of uncertainty about how effective the medication is. Also, we still have a lot of unknowns about drug interactions, adverse effects of the medication. We have no long-term data because ours is just short-term follow-up data.”
