Pharmaceutical CBD bests artisanal CBD in pediatric epilepsy syndromes

By Andrew D. Bowser

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While some parents have opted to try store-bought formulations of cannabidiol (CBD) as a treatment for children with epilepsy, there’s been little, if any, data to show how these artisanal formulations stack up, but one recent study now suggests the pharmaceutical version leads to higher blood concentrations of the compound and an improvement in seizure control.

The pharmaceutical-grade CBD (Epidiolex, Greenwich Biosciences) was associated with adverse events that included somnolence, emesis, decreased appetite, and diarrhea in the retrospective, 31-patient study, which included children with Lennox-Gastaut syndrome (LGS), Dravet syndrome, and other rare pediatric epilepsy syndromes. However, seizure control improved by nearly 40% in the prescription CBD group, compared with a decrease in seizure control in those children who received artisanal CBD preparations, according to researcher Nathan T. Cohen, MD, from Children’s National Hospital in Washington.

There is “clearly a difference” between the pharmaceutical and artisanal CBD groups, according to Dr. Cohen, though he cautioned that larger trials done under more controlled conditions would be needed to make more sweeping conclusions about the relative benefits of the two approaches.

Nevertheless, the findings do support the use of prescription CBD as another option in the armamentarium of treatments available to fight pediatric epilepsy syndromes, the researcher said in an interview.

“Even though it’s a small retrospective study, it is giving us information that helps us to frame that discussion with the families. It is more evidence to help families decide on the medication options that are best for their child,” Dr. Cohen said of the study, which was accepted as an abstract for the now-canceled 2020 American Academy of Neurology annual meeting and is planned to be submitted for publication in a peer-reviewed journal.

The pharmaceutical version of CBD, approved by the Food and Drug Administration in June 2018 for both LGS and Dravet syndrome, is relatively late to the game: Artisanal formulations have been around in some form since the late 1970s, and with more states allowing their sale, more parents of children with these syndromes are considering them as a treatment option, Dr. Cohen said.

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In 2020, CBD is fully legal for purchase in 33 states and Washington, D.C., legal with restrictions in 14 states, and completely illegal in only 3 states (Idaho, South Dakota, and Nebraska), according to World Population Review.

Dr. Cohen said he and his colleagues make it a practice to encourage parents to transition their child from artisanal to pharmaceutical CBD whenever appropriate. Artisanal CBD preparations are produced by any number of manufacturing techniques, and therefore contain varying amount of CBD or tetrahydrocannabinol (THC).

“What we would say to a family is that, when you use an artisanal or nonregulated product, even though they advertise a certain CBD concentration, it’s not necessarily subject to the same standards,” he said. “You don’t know what other types of compounds might be in there because they’re not subject to these regulations.”

There have been a few published studies looking at specific artisanal CBD preparations, though the results are mixed, and according to Dr. Cohen, there do not appear to be any studies that have specifically looked at the relative efficacy of artisanal CBD preparations versus that of prescription CBD.

In one 2013 report, researchers in the department of neurology at Stanford (Calif.) University surveyed parents participating in a Facebook group dedicated to sharing information on the use of cannabidiol-enriched cannabis to treat childhood epilepsy. Perhaps not surprisingly, 16 of 19 parents (84%) said this approach reduced their child’s seizure frequency.

Even though it’s a small retrospective study, it is giving us information that helps us to frame that discussion with the families. It is more evidence to help families decide on the medication options that are best for their child.

Most of those parents had used extracts they bought from a dispensary or direct from a medical cannabis grower. Those extracts are often inaccurately labeled, may have highly variable levels of CBD and THC, and could contain fungus, pesticides, or other contaminants that could lead to organ damage, according to the report, which appeared in Epilepsy & Behavior. Moreover, while CBD has a proven anticonvulsant effect, the data on THC is unclear, and in some cases, it has had a proconvulsive effect, according to the report authors.

A few more recent studies have looked at artisanal CBD preparations, including a retrospective analysis from researchers at Vanderbilt University, Nashville, Tenn., that indicated that adding CBD oil resulted in a 50% or greater reduction in seizures for 39% of pediatric epilepsy patients, with 10% becoming seizure free. By contrast, a recent prospective, observational study by researchers at the University of Colorado at Denver, Aurora, found that, in children with epilepsy, oral cannabis extract had a response rate on par with the placebo arm in randomized trials of CBD, with 14% of patients stopping oral cannabis extract because of an increase in seizure frequency.

Another recent prospective, open-label study from researchers in Rome found that an artisanal medical CBD oil had acceptable safety and a 50% or greater improvement in seizure frequency for about 40% of patients with developmental and epileptic encephalopathy, suggesting that randomized, placebo-controlled trials of the oil might be warranted.

In the present study by Dr. Cohen and colleagues, the investigators sought to confirm their hypothesis that treatment with pharmaceutical CBD would lead to higher serum levels of the compound than artisanal CBD. They included 22 patients participating in an expanded-access program for pharmaceutical CBD and 9 patients who received artisanal CBD. About half of the patients (48%) were female, and the mean age was 10.1 years. About one-third (32%) had LGS, while 6% had Dravet syndrome, and the rest (62%) had other epilepsy syndromes.

They found that the mean serum CBD level was indeed higher in the pharmaceutical group, at 124 ng/mL versus 30.1 ng/mL in the artisanal group, according to their report. With a median follow-up of 11.8 months, 39% of the prescription CBD group had a reduction in overall seizures, while by contrast, 70% in the artisanal CBD group had an increase in overall seizures. Adverse effects including somnolence, emesis, diarrhea, and decreased appetite were reported in 11 patients, all in the pharmaceutical CBD group, and of those, 6 discontinued treatment because of side effects.

Given the widespread use of these products, whenever possible, I think it’s good for physicians to point families back toward whatever evidence, although limited, may help them make the safest decision.

“Ultimately, this is a smaller-scale, retrospective study that provides some evidence that suggests that there may be a difference in efficacy between the use of pharmaceutical-grade CBD and artisanal CBD,” Dr. Cohen said in the interview. “Given the widespread use of these products, whenever possible, I think it’s good for physicians to point families back toward whatever evidence, although limited, may help them make the safest decision.”

Dr. Cohen and coauthors reported that they had no disclosures related to the research.

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