Putting Charlotte’s Web to the (clinical) test

There’s a lot to get excited about with Charlotte’s Web, the cannabis oil featured on this week’s “TechKnow” that appears to drastically reduce, or even stop entirely, massive and debilitating seizures in kids with severe epilepsy. But even setting aside the obvious controversy — should parents be treating their children with medical marijuana? — there’s still a lot that’s not yet known.

Even though Jesse Stanley, whose dispensary developed Charlotte’s Web, has a waiting list of thousands of families eager to get access to the drugs, he understands that federal distribution and wider acceptance are still a work in progress.

“There's a lot of people that will not accept the medicine unless there's been studies on it,” Stanley says.

“I’m one of those people,” replies “TechKnow” contributor and molecular neuroscientist Crystal Dilworth.

While Dilworth says there’s a clear compassionate-use argument for the Colorado families using Charlotte’s Web — most showed little to no progress with traditional, Western pharmaceuticals — any larger use of this or similar treatments raises some big questions.

#1: WHERE’S THE RESEARCH?

Though the Stanley brothers pride themselves on consistent production standards and closely monitor the drug’s impact with families, as well as using blood tests to determine and adjust dosing amounts, Charlotte’s Web has not been a part of any FDA-approved studies.

“The pipeline that we use to approve drugs is there for a reason,” Dilworth says. “First we worry about whether we can keep cells in a dish alive when treated with the drug, and then whole organisms — animals — and then once we’re able to model those results in an animal population, that’s when we tentatively move forward with small human studies. Then larger human studies. What they’re doing here is working backwards, starting with human trials. They have not given Charlotte’s Web to rats.”

According to Dr. Maria Cilio, a professor of neurology and pediatrics at the University of California, San Francisco, who is working with GW Pharmaceuticals on the first clinical trial of CBD, “The use of CBDs have been going on for many years. We don't have enough data in order to say whether this drug is safe or effective. The only thing (a review of earlier studies could prove) was that a range of 200 to 300 mg per day for adults was safe. The American Epilepsy Society said they cannot recommend the use of this product in the treatment of epilepsy. They didn't say no — just we don't have enough data, we can't recommend.”

#2: HOW DO YOU PROVE CBD IS THE MAGIC INGREDIENT?

“We assume that because Charlotte’s Web is so high in cannabidiol, or CBD, that it is what is causing the change in seizures,” Dilworth says, but the process used by the Stanley brothers doesn’t isolate pure CBD or account for the impact of other ingredients used in making the oil, such as the food-grade alcohol or olive oil. “You can’t really make the statements about what’s working if you don’t know for sure.”

The GW Pharmaceuticals trials seen in “TechKnow” are not testing Charlotte’s Web. “It's not a preparation, it's a pharmacological compound,” says Cilio. “Pure CBD is only obtainable in the lab. There is always a small percentage of THC in the artisanal preparation, including Charlotte's Web.”

The Stanley brothers are concerned that if pure CBD trials aren’t successful, it could be confused with poor results for Charlotte’s Web. But, Dilworth says, “If the GW single-compound study doesn’t produce positive results, it is entirely possible that Charlotte's Web extract is special because it contains a certain ratio of other molecules that are necessary for seizure cessation. It is not uncommon for multiple compounds to act synergistically to exert a unique physiological effect — neuroscientists call this ‘potentiation.’ CBD could still be the important molecule, but it might need help from others to be fully effective — and the scientist in me thinks that would be so cool.”

#3: WHAT’S THE LONG-TERM IMPACT OF MEDICAL MARIJUANA IN KIDS?

While marijuana is considered very safe, there’s plenty about the long-term toxicity of cannabis products — especially when used by children — that’s unknown.

“Cannabinoids are fat-soluble,” Dilworth says, “so they stay in your body a long time. What if your body starts to break it down and stores other parts of the compound? We don’t know how children metabolize this. They metabolize milk differently than adults do, so this could be different, too. Pediatric application opens a whole new can of worms.”

In the GW trial, Cilio says, “we are monitoring the child very frequently. If the child is drowsy, we want to see if there are changes in the liver function, if the drug might impact the liver or the kidney. We don't expect to see adverse events — otherwise I wouldn't try this drug in young children — but we are there with eyes wide open with any change for any side effect related to this treatment.”

To learn more about medical marijuana and Charlotte's Web, watch "TechKnow," Sunday 7:30ET/4:30PT.