In a first, scientists show marijuana component cannabidiol reduces seizures for some with epilepsy

STAT/May 24, 2017/Andrew Joseph

For the first time, scientists have demonstrated that a component of cannabis reduces seizures in children with a rare form of epilepsy, marking a significant step in efforts to use marijuana and its derivatives to treat serious medical conditions.

The company that sponsored the Phase 3 trial, GW Pharmaceuticals, had already announced some of the results, but researchers said the full peer-reviewed study, published Wednesday in the New England Journal of Medicine, validated the importance of the research. They also pointed out that the drug, cannabidiol, helped some patients more than others and was associated with a range of sometimes severe side effects, a significant finding because some families have been treating their children on their own in states where recreational marijuana use is legal.

“We now have solid, rigorous scientific evidence that in this specific syndrome, cannabidiol is effective at reducing seizures,” said Dr. Orrin Devinsky, a neurologist at New York University Langone Medical Center and an author of the new study. But, he added, “This is not a panacea.”

Cannabidiol, which GW has branded as Epidiolex, is a non-hallucinogenic component of marijuana that can be purified and administered in oil.

For the trial, researchers enrolled 120 children from 2 to 18 years old with Dravet syndrome, a rare genetic form of epilepsy that kills up to 20 percent of patients by the time they are 20. There are no drugs approved specifically for Dravet.

During the study, the patients stayed on their normal treatment regimen, and half of them also received cannabidiol while the remainder were given a placebo. Over a 14-week treatment period, the median number of convulsive seizures in the cannabidiol group decreased from 12.4 to 5.9 per month; for the placebo group, the number went from 14.9 to 14.1.

In the cannabidiol group, 43 percent of patients had their number of seizures cut in half or more, compared with 27 percent in the placebo group. And 5 percent of patients taking cannabidiol saw their seizures disappear, compared with none in the placebo group.

Common side effects seen in the cannabidiol group included vomiting, fatigue, fever, drowsiness, and diarrhea. Eight patients in the group withdrew from the trial because of the severity of the side effects.

In an editorial published with the study, Dr. Samuel Berkovic of the University of Melbourne called the trial “welcome” and “the beginning of solid evidence for the use of cannabinoids in epilepsy.” But he noted that it needs to be replicated and that other studies will be required to know if cannabinoids — the different components of cannabis — can help with other forms of epilepsy and to treat adults.

As desperate families have sought to treat their children with cannabis or cannabidiol on their own, experts have cautioned that it can be risky. Researchers don’t know, for example, how cannabidiol will interact with other medications, and they know even less about how adding THC — a hallucinogenic cannabinoid — to the mix might affect children with epileptic syndromes. They also don’t know the long-term effects of taking cannabidiol.

“We just have to be humble,” Devinsky said. “People have jumped to the idea that cannabis-based products are natural and therefore they work well, and all these anecdotes support that. There’s a lot of belief, and not a lot of science.”

The latest study was a randomized, double-blind, placebo-controlled trial, considered the gold standard form of research. Experts say that these types of trials are the only way to determine if cannabinoids are truly effective at treating diseases.

“The data to me are persuasive,” said Dr. Igor Grant, of the Center for Medicinal Cannabis Research at the University of California, San Diego, who was not involved with the study. “They do show that not everyone gets well, and that’s an important point. But there were substantially better outcomes in the cannabidiol group.”

GW has also announced the results of two Phase 3 trials for cannabidiol in another form of epilepsy called Lennox-Gastaut syndrome, the full data from which have not been published. The company plans to ask the Food and Drug Administration this year to approve Epidiolex for both syndromes.

“We do see it as profoundly important that patients suffering from these difficult-to-treat conditions have access to an FDA-approved medication, which is manufactured to the standards that medicines are meant to be manufactured to, where the safety profile is well-characterized, and where the dosing is well understood,” GW CEO Justin Gover said in an interview.

An FDA approval of Epidiolex could also lead to a change in US drug policy. Cannabis is classified as a Schedule I drug, defined as having a high potential for abuse and no medical value. But an approval would signify that cannabis — or at least cannabidiol — does have a medical use.

The Drug Enforcement Administration could reschedule only cannabidiol and leave cannabis generally at Schedule I. But some scientists who complain that the scheduling makes valid research on cannabis burdensome — they have to get special approval and meet security protocols to study cannabis — hope that the potential of cannabidiol as a medicine could push the DEA to reschedule cannabis itself.

For now, researchers are not sure why some children saw better responses to cannabidiol than others, or even how the drug reduces seizures. But they said this study will likely lead to others exploring those questions and if cannabidiol or other cannabinoids can help with other conditions.

“It’s really a welcome development that they had a well-controlled trial, it’s a big step forward,” said Ivan Soltesz, a neuroscientist at Stanford University, who was not involved with the study. But, he said, “it’s a little bit of a mystery about how it actually works.”

Mexico Begins Importing Medical Marijuana As Views on Therapeutic Cannabis Evolve

Mexico Begins Importing Medical Marijuana As Views on Therapeutic Cannabis Evolve

LA Weekly/December 23, 2016/Alicia Lazano

HempMeds, a subsidiary of Medical Marijuana Inc., has formed the first cannabis-based export partnership to Mexico, Brazil, Paraguay, Argentina and Chile with its export of Real Scientific Hemp Oil and its THC-free counterpart, Real Scientific Hemp Oil-X. The plants for these treatments are grown in northern European microclimates and claim to be free of pesticides and herbicides.

The California-based company’s partnership with Mexico — an ally of particular interest thanks to cultural and historical ties that date back centuries — was solidified earlier this year when Cofepris, the Mexican health department, approved the country’s first permit allowing the import of hemp-based CBD oil across its border. The announcement came after years of intense pressure on Mexican authorities from medical marijuana allies and advocates pleading on behalf of two families with children who have severe forms of epilepsy. Recently, Mexico also eased up on its no-THC stance and passed the country’s first medical marijuana legislation. Many in Mexico see the move as a step toward eventually legalizing pot in a nation drowning in drug violence.

“Despite the terrible cartel violence, the regulatory authority in Mexico saw the potential for CBD,” says Stuart Titus, CEO of Medical Marijuana Inc. “Today we remain the only legal, cannabis-based products allowed into the country.”

The road to Mexico’s evolving stance on marijuana begins with Alina Maldonado Montes de Oca, a young girl from the small town of San Andres Tuxtla in the state of Veracruz. She had her first seizure when she was just an infant. They increased almost immediately, peaking at 25 to 40 small attacks per day, with grand mal seizures striking up to twice per week. Doctors found that she had hypoxia, an oxygen deficiency to certain parts of the body, which affected her brain development and caused both epilepsy and infantile cerebral palsy. Maldonado was treated with 14 different kinds of medication, each one with an array of painful side effects, including liver damage and gastritis.

Eventually Maldonado’s father came across a similar case in the United States that was treated successfully by CBD. Cannabidiol has been gaining traction stateside as an alternative to harsh drugs after several American studies showed that it can drastically reduce the number of seizures in small children with Lennox-Gastaut (LGS) and Dravet syndromes.

But in Mexico, cannabis-based treatment is viewed with suspicion and remains highly taboo. So when the Maldonado family discovered that another Mexican family had a child with the same kind of disorder, the two families combined their efforts and participated in a series of congressional hearings in Mexico City in January. On Feb. 1, 2016, they were rewarded when Cofepris granted permits for the little girls to receive CBD treatments from abroad.

“We are very humbled to have this opportunity,” Titus says. “Our products seem to work when traditional medications haven’t been able to control these seizures.”

Conditional permits for CBD are not unprecedented — a Mexican judge sanctioned similar treatments last year to a third girl — but the medication is strictly regulated. All imports must be free of tetrahydrocannabinol (THC) and contain no psychoactive properties. In other words, they cannot get patients stoned. Brazil has a similar arrangement with Medical Marijuana Inc., whose hemp oil was first allowed in the country in 2014 on a case-by-case basis for the treatment of chronic pain, epilepsy and Parkinson’s disease.

“We helped educate the government [in Brazil] and, going further, the government saw this product actually helped control these seizure disorders. Since there wasn’t a good pharmaceutical medication, the regulatory officials declared it would be inhumane to keep these products from the patients,” Titus says.

HempMeds now is treating approximately 1,500 families with epileptic children in Brazil, comprising approximately 40 percent of juvenile patients, Titus adds. Brazilian authorities also have approved the import of marijuana-based treatment for a woman with Zika virus.

The idea that cannabis-based products are making their way into countries historically tied to drug trafficking is an irony not at all lost on Titus, who traded in a career on Wall Street to become first a physical therapist and now the CEO of the U.S.’ first publicly traded marijuana company.

“Here we’ve developed a reverse cannabis pipeline,” Titus says. “But it’s been very interesting — even some of the elite people in Mexico are underground cannabis connoisseurs. They all love the best American-grown cannabis.”

Part of the allure in spreading operations throughout Latin America is the region’s cultural connection to alternative medicine. Unlike the United States, where big pharmaceutical companies largely determine which treatments are in vogue, doctors south of the border regularly prescribe homeopathic cures to their patients. That marijuana comes mired with a bad reputation is just one more obstacle to overcome in a global economy already becoming more weed-friendly.

“It’s been years that we’ve been fighting for acknowledgment and approval and recognition of the medical and therapeutic uses of cannabis, and today we finally have something,” said Lisa Sanchez, director of drug policy for Mexico Unido Contra la Delincuencia, a group working to curb crime.

Titus first came across medicinal marijuana while treating athletes recovering from sports injuries in North Carolina. Since then, he has been increasingly interested in alternative medicine and botanical solutions. He says “Latin America’s connection to nature” is something we in the north should seek to emulate. “All modern medicines came from plants,” he says. “We’ve moved away from that and now only look at synthetic medicine. It’s a shame.”