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As CBD skyrockets in popularity, scientists scramble to understand how it’s metabolized

Everything from bacon consumption to kidney function can skew cannabidiol dosing.

In November of 2017, scientists at a subsidiary of Artelo Biosciences in Manchester, UK, tasked an intern with compiling any scientific study published on the body’s absorption, distribution and metabolism of cannabidiol. The company hoped to treat stroke with the compound, which is derived from the cannabis plant and commonly known as CBD, and this background research was crucial.

When the intern returned with all the literature she could find, it was a short stack: only a couple of dozen papers. The scientists were stunned. They’d expected more from a molecule receiving so much attention from the biomedical world and consumers. As they surveyed the scant literature, they wondered: is this all there is?

The desire for more information about how CBD acts in the body is growing as various companies pursue it in drug development. It’s only in the last decade that the first CBD drugs have been approved: Sativex for multiple sclerosis symptoms, in multiple countries; and Epidiolex for certain kinds of epilepsy in children, in the United States. GW Pharmaceuticals, the maker of both medications, expects European Union approval for Epidiolex soon. Beyond that, there are dozens of ongoing clinical trials for conditions ranging from schizophrenia to Crohn’s disease to graft-versus-host disease—not to mention the appearance of CBD in consumer products ranging from oils to coffee to tampons.

“CBD is exploding in popularity,” says Nick Jikomes, a neuroscientist and principal research scientist at the cannabis information site Leafly, in Seattle. “It seems that every corner store you walk into is selling a CBD something or other.” In the United States alone, a recent Gallup poll found 14% of Americans use CBD products, and the CBD market is projected to top $20 billion per year by 2024, according to one analysis.

CBD could, potentially, treat such a wide variety of conditions because it binds to various receptors in the body, particularly in the endocannabinoid system, which is involved in pain, mood, metabolism, reproduction, and more. These receptors are found in the nervous system, as well as many other tissues, including heart, liver and immune cells. CBD can cause side effects such as nausea, fatigue and irritability, but doesn’t make people feel high.

Considering that people have used cannabis for millennia, scientists still know surprisingly little about how CBD, often the second most prevalent active compound in the plant, is absorbed and metabolized by the body. “Unfortunately,” Jikomes adds, “we don’t have the information we would like to have about dosing.”

The lack of reliable data on dosing means that some clinical trials might fail not because CBD doesn’t help, but because they didn’t use the right amount. Other trials may land on a dose that’s OK, but doesn’t maximize benefit while minimizing side effects.

Many patients aren’t waiting around for more information on dosing. They are eager to try CBD products for many different ailments and going to their physicians for guidance. But in a recent review, physicians noted that many clinicians don’t know how much CBD to prescribe, especially if they venture beyond well-understood indications such as epilepsy and psychosis4.

It would help if doctors had formulas to predict a starting dose for a given individual with a particular condition, says Jennifer Martin, a pharmacologist and physician at the University of Newcastle in Australia. For many other medications, such as antibiotics, doctors and pharmacists can enter a patient’s characteristics—such as age, sex, or kidney function—into such equations to receive a suggested dosage. This can be particularly helpful if trials haven’t offered up dosing data for every possible patient group, such as people of certain races, Martin says. She is working on such formulas for CBD and THC, another prominent cannabis compound that is responsible for marijuana’s higbut also has medical benefits.

CBD’s behavior makes it tricky to understand. It may bind to different cell receptors in the endocannabinoid system and beyond—including receptors in the serotonin, opioid and dopamine systems6. And where it binds depends on the dose, Jikomes says. At different concentrations, “it can essentially behave as a different drug,” he says. So, more isn’t necessarily better. In fact, in one study, antianxiety effects peaked after a 300-milligram dose; 900 milligrams proved less effective7.

Another complication: CBD is oil-soluble. The amount of drug absorbed into the bloodstream increases if it’s taken with food or infused into oils. GW reported in its 2018 study that plasma concentrations more than quadrupled when the liquid medicine was taken with a high-fat meal including fried eggs and bacon, compared to the medicine alone. CBD can also be absorbed by the body’s fat stores and released later.

All of this means that the ideal prescription will vary by many factors, including but not limited to sex, weight and medical conditions. In the case of the Sativex mouth spray, new users start with one spritz in the evening and slowly work up to an effective dose, with a maximum of 12 sprays daily. Sativex also contains THC, so patients can feel when they’ve had too much. With Epidiolex, kids start at 5 milligrams per kilogram body weight per day, but can go as high as 20 milligrams if needed to reduce seizures.

Whatever the indication, the best approach is to start with a low dose and raise it slowly over up to two weeks, says Ethan Russo of Vashon, Washington, director of research and development for the International Cannabis and Cannabinoids Institute in Prague.

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Posted on: September 11 2019

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