Jason White, who chairs the World Health Organization Expert Committee on Drug Dependence, told me he believes CBD will prove efficacious for a broader range of seizure types, that it likely has some anti-psychotic efficacy, and that it may help improve the quality of life among those who suffer from Parkinson’s disease. In studies, CBD has been found to treat certain types of seizures, has benefited schizophrenia patients with psychotic symptoms in two of three RCTS, and has improved activities of daily life and sleep in Parkinson’s patients in early trials.
Does it, though? The question of what pure CBD (without THC) has been proven to treat is genuinely difficult to answer. Much of the peer-reviewed research looks at CBD as a medicinal drug or includes cannabis in the study. In a review of 79 randomized clinical trials (RCTS) of cannabinoids for the below indications, the authors found moderate-quality evidence for cannabinoid use for the treatment of chronic pain and spasticity, and only low quality evidence for improvements in vomiting resulting from chemotherapy, weight gain in HIV infection, sleep disorders and Tourette syndrome. But the study was limited because it included multiple cannabinoids that were evaluated at different doses by different routes, with many products containing THC.
I visited three stores in the San Diego area. At the Golden State Greens shop, the supervisor, Jake C. told me his customers use CBD primarily for stress, anxiety, insomnia and pain, including several cancer patients who found that the product helped them sleep and perhaps regain some weight they’d lost while undergoing treatments. Shawn McManigal, owner of the Injoi CBD store in La Jolla, said a 92-year-old customer of his stopped taking his constipating pain medications after realizing that CBD gummies relieved the pain and allowed him to rest. “I’m not saying this is a miracle cure,” McManigal told me, “but there is science behind it and it really proves what it does.”
As for potential users, “low and slow” was the refrain from the CBD store managers with whom I spoke. With CBD tincture, for example, McManigal recommended placing a half of vial of oil under the tongue—the equivalent of 17 milligrams in his formulation—and waiting 45 minutes to an hour. “If you don’t feel the effect of being more relaxed, use more,” he said.
According to a WHO report, CBD is generally well-tolerated with a good safety profile, and in humans it exhibits no effects that would indicate potential for abuse or dependence. The side effects are generally mild and may include sleepiness, diarrhea, mood changes, etc., but concerns exist of potential liver injury, medication interactions, and male fertility issues. White said there is little known about the effects of sustained and/or cumulative use of CBD, or its use in special populations like adolescents, the elderly and pregnant women.
CBD’s popularity has skyrocketed because of its purported therapeutic benefits, along with a low potential for abuse. There’s also plenty of it, and it’s profitable. According to Julian Wright, Founder of Science and Recreation, farmers can make $60,000 per acre to produce hemp high in CBD, versus $750 per acre in hemp sold for fiber. The commercial market for CBD, meanwhile, is projected to rise from an estimated $500 million in 2018 to $1.8 billion by 2022.
But as the days passed, I began to glimpse the other side of the conversation. In the end, I spent quality time with the supervisors of three CBD stores in my area, and each had inspiring stories to share of customers who alleviated their aches, overcame chronic pain, reduced stress, had a good night’s sleep or got a semblance of their lives back. They told me stories like that of Lorraine, who had been bucked off a horse, broke some vertebrae, was ridden with chronic pain, yet experienced such dramatic improvement with CBD that after a month, she rode her horse 400 miles through the south of Spain.
Even though humans have been using cannabis for thousands of years, the products available today are not the cannabis that has traditionally been consumed. After cannabis was prohibited at the federal level in 1970 by the US Controlled Substances Act, illicit growers were incentivized to breed strains that had higher amounts of THC, so they could increase their profits without needing larger growing spaces. What they didn’t know was that by driving up THC content, they were dramatically reducing the CBD content. In 1995, after decades of surreptitious breeding, the ratio of THC to CBD was
Right now, the most significant side effect of CBD we’ve seen is its interaction with other drugs. CBD impacts how the human liver breaks down other drugs, which means it can elevate the blood levels of other prescription medications that people are taking — and thus increase the risk of experiencing their side effects. And women who are pregnant or who are expecting to be should be aware of this: We don’t know if CBD is safe for the fetus during pregnancy.
Is CBD a cure-all — or snake oil? Jeffrey Chen, executive director of the UCLA Cannabis Research Initiative, explains the science behind the cannabis product.
So where does this leave us? Unfortunately, outside of certain rare pediatric seizure disorders, we scientists do not have solid data on whether CBD can truly help the conditions that consumers are flocking to it for — conditions like insomnia, depression and pain. And even if it did, we still need to figure out the right dose and delivery form. Plus, CBD is not without side effects. Here’s the advice that I give to my friends and family: If you’re using CBD (or thinking about using it), please research products and talk to your doctor so they can monitor you for side effects and interactions with any other drugs you take.
While CBD appears to be generally safe, it still has side effects. In children suffering from severe epilepsy, high doses of CBD have caused reactions such as sleepiness, vomiting and diarrhea. However, we don’t know if this necessarily applies to adults using CBD because these children were very sick and on many medications, and the equivalent dose for an average 154-pound adult would be a whopping 1400 mg/day. And while CBD use in the short term (from weeks to months) has been shown to be safe, we have no data on what side effects might be present with chronic use (from months to years).
15:1, and by 2014 the ratio had jumped to
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.
When Martin searched the literature for CBD dose-guidance equations for a recent review, she, like Millar, came up short. She couldn’t find even one paper that met her criteria: intravenous dosing and reporting of individual patient bloodstream concentrations. In contrast, 12 studies were available for THC, which has a longer clinical history.
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."
Dearth of data
The team went further in a second article, analyzing the doses used in 35 clinical studies. The papers were a “mixed bag,” notes study co-author Andrew Yates, a consultant at Artelo Biosciences. The conditions under study included anxiety, diabetes, chronic pain and more. Doses ranged from less than 1 to 50 milligrams per kilogram body weight per day, but no study reported CBD plasma concentrations. About two-thirds of the studies reported CBD to be associated with improved outcomes.
Another issue is that CBD is a botanical, from a plant that makes more than 100 compounds that come only from cannabis, called cannabinoids, plus other potentially bioactive molecules such as terpenoids. Cannabis extracts available over the counter contain varying amounts of CBD itself, along with other compounds. Indeed, some over-the-counter products, upon testing, turn out to have no CBD at all. Even if some CBD is present, it’s probably not enough to have an effect, says Hazekamp. “People are massively underdosing themselves.”
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.
In November of 2017, scientists at a subsidiary of Artelo Biosciences in Manchester, U.K., 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.