Children with refractory epilepsy who took pharmaceutical cannabidiol (CBD) had higher serum CBD levels and better seizure control than those who took artisanal CBD, but they had more adverse side effects, preliminary results of a small study indicate.
Given the widespread use of artisanal CBD products, Nathan T. Cohen, MD, pediatric epilepsy fellow, Children's National Hospital, Washington, DC, and his colleagues wanted to know how these products differ from pharmaceutical grade CBD with respect to seizure control.
"One of the challenges or questions we have is whether there is any information that would guide us and suggest patients transition from artisanal to pharmaceutical grade CBD," Cohen, who is lead author of the study, told Medscape Medical News.
The findings were released February 27 in advance of being presented at the upcoming American Academy of Neurology (AAN) 2020 Annual Meeting in April. The study received no outside funding.
In addition to helping relieve anxiety and stress, CBD, one of many constituents of Cannabis sativa, or the marijuana plant, has antiseizure properties. The US Food and Drug Administration (FDA) has approved a pharmaceutical CBD (Epidiolex, GW Pharmaceuticals) for the management of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome.
This purified oral CBD prescription product does not contain tetrahydrocannabinol (THC), the component of marijuana that produces a "high."
Artisanal CBD, which has been around since the late 1970s, is manufactured using variable amounts of CBD and THC. Artisanal products, which typically come in the form of oils that are swallowed, are available in dispensaries and elsewhere, depending on the legal status in individual states.
These artisanal formulations are popular among patients with epilepsy and their families. On the basis of the advertising he sees, Cohen estimates there are at least 100 artisanal CBD products, but he was quick to stress he's not an expert on artisanal CBD.
He noted that some families are "searching for an alternative treatment" to help control their child's seizures, and if the seizure syndrome isn't LGS or Dravet, "then technically, they don't qualify for prescription-strength CBD," said Cohen.
The current study was a retrospective chart review and included patients with epilepsy who underwent treatment with artisanal or pharmaceutical CBD for whom serum CBD levels were available.
In addition to CBD levels, the researchers had information on patients' date of birth, gender, epilepsy diagnosis, artisanal or pharmaceutical CBD dose, seizure history, and side effects, among other things.
The analysis included 31 patients (48% female; mean age, about 10 years). Of these, 32% had LGS, 6% had Dravet, and the rest had other epilepsy syndromes.
Of the total, 22 patients participated in a pharmaceutical CBD expanded-access program. The remaining nine patients received artisanal CBD.
The mean serum CBD level was 30.1 ng/mL in the artisanal group and 124 ng/mL in the pharmaceutical group.
Cohen noted that artisanal products contain lower amounts of CBD because they're not purified, and they may contain other compounds derived from marijuana.
At the last follow-up, which was a median of 11.8 months, patients who took artisanal CBD had a 70% increase in overall seizures. Cohen pointed out that some of the hundreds of compounds in marijuana could be "pro-convulsant."
Some Seizure Free
The prescription CBD group experienced a 39% reduction in seizures. "Some of these kids had up to hundreds of seizures a day and went down to tens, and some kids became seizure free," said Cohen.
Because the study was "looking back in time," the investigators couldn't determine whether age, type of epilepsy, or other factors affected seizure control in the two groups, said Cohen. "One of the limitations of a retrospective study is that we're not able to control for those factors," he said.
Eleven patients ― all in the prescription CBD group ― reported adverse effects, including somnolence, emesis, diarrhea, and diminished appetite; six discontinued CBD because of side effects.
Cohen said he's not aware of any study that has compared artisanal products "head to head" with pharmaceutical grade CBD. "The whole point of this study was to ask the question, Is there a difference between the groups?, and these new data would suggest that there may be."
The results appear to support giving encouragement to patients to transition from artisanal to pharmaceutical CBD if appropriate. "Anytime you're giving your child a medication that has not been produced under the stringent guidelines that all pharmaceutical FDA-approved medications undergo, you don't know exactly what's in the product, and not knowing is a potential issue," said Cohen.
The findings need to be studied in a more controlled setting "to make sure they're valid," said Cohen. Because this is "a very hot topic," he's keen to see what further research his colleagues would be interested in pursuing.
Commenting for Medscape Medical News, Joseph Sirven, MD, a neurologist in Scottsdale, Arizona, said this is an important study.
"It highlights one of the most common questions that I receive almost on a daily basis in my neurology practice," he said.
Most people think that dispensary-based CBD is the same as prescription-based CBD, said Sirven. "Technically and theoretically, they certainly could be; however, what this study highlights is that in practice, they are not the same."
He stressed that prescription CBD has to meet certain quality standards. "That means that whatever the ingredient list states about the concentration of CBD in the product has to be within the product, which is why the FDA approved it. It is, in essence, a quality control issue."
A dispensary-based product does not need to meet such stringent standards and so "is subject to whatever the manufacturer chooses to put in the product," said Sirven.
The study received no outside funding. Cohen and Sirven report no relevant financial relationships.
American Academy of Neurology (AAN) 2020 Annual Meeting: Abstract 710.
Medscape Medical News © 2020
Cite this: Artisanal CBD May Provide Less Seizure Control Than Pharma CBD - Medscape - Mar 03, 2020.