Friday, September 11, 2015

The stratospheric rise of medical marijuana

The stratospheric rise of medical marijuana as a possible recognized treatment for epilepsy, now underway, is an example of what can be achieved through the sharing of personal stories on the Internet and social media, according to a leading expert in the field.

Daniel Friedman, MD, New York University (NYU) Langone School of Medicine, is a coauthor a review article, "Cannabinoids in the Treatment of Epilepsy," published in the September 10 issue of The New England Journal of Medicine.

"It is a very interesting mix of science, politics, and social phenomena which has moved medical marijuana to the forefront of treatment for severe drug-resistant epilepsy," he commented to Medscape Medical News. "Two years ago the epilepsy community wasn't really seriously considering this as an option. But it has now really taken off."...

"This has come about because individuals have shared anecdotal experiences about its effectiveness in children with severe intractable epilepsy on the Internet and these have spread across the globe," he added. "Once it became 'out there,' families have been clamoring for access to the product and we have had to pay attention. That is why medical marijuana is being legalized and studies are finally being done."...

"It's very much 'watch this space' at the moment," Dr Friedman commented to Medscape Medical News. "There is emerging evidence on efficacy. The preclinical evidence is reasonably strong for cannabidiol, similar to that for a new pharmaceutical for epilepsy. The clinical data are still early. So far the studies have been small and methodologically flawed, but results are encouraging."...

"There are regulatory issues because these are all schedule I compounds they have many restrictions, so clinical trials have too many additional layers of regulatory bureaucracy," he said. "Then there is the issue of public perception: there is a disconnect between what we know about efficacy from scientific literature and what the public perceive the evidence to be. Many states have legalized medical marijuana for several conditions, including epilepsy, so there is the perception that it has been proven to work, but this is not the case. I worry about the high expectations — this could confound clinical trial results by leading to a very high placebo response."...

He also pointed out a problem with the variability in the regulation of cannabinoid products available. "In some states there is a high degree of regulation with external testing of products to verify the cannabidiol/THC content. But in other states, it is left to the individual dispensaries to stipulate the content and there is no external validation, so you can't be sure what you're getting," he said. "It's a bit like health supplements — a product may say it contains 1000 units of vitamin C but when tested it often has nowhere near this amount in it."...

Dr Friedman noted that other products derived from hemp are legally available on the Internet and are touted as having a high cannabinoid content, "but a recent FDA [Food and Drug Administration] analysis of some of these products found big discrepancies in this and some contained no cannabinoids at all."...

In their review, however, Dr Friedman and Dr Devinsky conclude, "Only double-blind, placebo-controlled, randomized clinical trials in which consistent preparations of one or more cannabinoids are used can provide reliable information on safety and efficacy.

"If randomized clinical trials show that specific cannabinoids are unsafe or ineffective, those preparations should not be available," they add. "If studies show that specific cannabinoids are safe and effective, those preparations should be approved and made readily available."

Friedman D, Devinsky O. Cannabinoids in the Treatment of Epilepsy. N Engl J
Med. 2015 Sep 10;373(11):1048-1058.

1 comment:

  1. Researchers are reporting further positive results using an investigational product containing pure cannabidiol (Epidiolex, GW Pharmaceuticals) in children with intractable epilepsy.

    Francis Filloux, MD, chief, Division of Pediatric Neurology, University of Utah, Salt Lake City, reported study results from his center, one of several across the country that participated in an expanded-access investigational new drug program launched by GW Pharmaceuticals.

    They found a reduction of the total number of seizures by a median of 38% at 3 months and 31% at 6 months.

    The findings were presented during the recent Child Neurology Society (CNS) 2015 Annual Meeting.

    The study included children and young adults who had drug-resistant epilepsy. Participants included those with Dravet syndrome, Lennox-Gastaut syndrome, early-onset epileptic encephalopathies of mixed type, intractable epilepsy of unknown cause, and structural lesions.

    These patients started on a cannabidiol (CBD) dose of 2 mg/kg per day, which was increased to a maximum tolerated dose or to 25 mg/kg per day.

    The product is a highly purified extract from the marijuana plant that is prepared in an oil-based liquid. Dr Filloux has been told by some older verbal patients that the taste can be somewhat offensive. It has no psychoactive properties, he noted...

    More than three quarters (77%) of the 22 remaining patients experienced fewer seizures after 6 months.

    Surprising Response

    One patient, a female young adult whom researchers believe has complex partial seizures secondary to brain toxicity from leukemia treatments, became seizure-free after the first dose.

    "That was surprising" because evidence suggests that children with Dravet syndrome might respond best to CBD, said Dr Filloux. "I was predicting that if anybody would respond that dramatically, it would probably be a patient with Dravet syndrome."

    A few patients with Dravet syndrome did experience a dramatic response, but only temporarily, he said.

    Even now, close to a year later, the patient with the almost immediate response continues to be seizure free, Dr Filloux told Medscape Medical News.

    With such a dramatic response, some experts were skeptical that the patient even had epilepsy, said Dr Filloux. "But there's absolutely no question that the patient had epileptic events because we had monitored her with video EEG [electroencephalographic] monitoring before the study started."

    Other sites, too, are reporting equally dramatic responses. "I think that 8% to 10% of patients have had 100% seizure control, so there is a small subset across all sites where similar benefits are being observed," said Dr Filloux.

    In addition to seizure control, parents of the Utah patients reported other benefits of the drug at 3 months, such as improved alertness (40%), greater sociability (40%), and decreased irritability (24%). Some parents also reported that their child had better sleep and a "burst" in developmental progress, said Dr Filloux.

    However, he stressed that the study was uncontrolled, symptoms were self-reported by families, and there has been a lot of news coverage of medical marijuana for the treatment of epilepsy.

    "Many parents had been avidly desirous of their child going on this cannabidiol because of what they had read in the lay press, so they were primed to believe this cannabidiol might be beneficial."

    On the other hand, he said, it's important to keep in mind that these children have "horrible epilepsy" and most have been on more than 10 medications for seizure without success. "Any improvement to that degree in this population that is sustained is a pretty dramatic response."

    The main adverse effects were mild diarrhea and appetite changes, which were expected. Seven serious adverse events occurred, but none were deemed related to the study drug.