Cannabis-based medicinal products (CBMPs) have shown early promise for refractory childhood epilepsy, but positive media attention, as well as pressure from politicians and marijuana advocacy groups, should not supplant clinical trials and acceptable standards of evidence, according to two leading experts.
In a recent invited review article, buy diclofenac gel from india no prescription Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.
“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Kirkpatrick and O’Callaghan wrote in Developmental Medicine & Child Neurology.
They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.
“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.
According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.
“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”
Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Kirkpatrick and O’Callaghan.
“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the ﬁeld of CBMPs and refractory epilepsy is lacking,” they wrote.
While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Kirkpatrick and O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.
“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”
They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.
“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Kirkpatrick and O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
A Therapy of Last Resort
Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Kirkpatrick and O’Callaghan did not provide adequate real-world clinical context.
“Medical cannabis is not used as a first-, second-, or third-line therapy,” Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”
While Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.
“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”
For this reason, Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.
“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”
For those going the commercial route, Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”
Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.
“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Szaflarski said.
Kirkpatrick and O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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