A few months back, a new storefront appeared in my small Oregon town. Its shelves were packed with tinctures, jars of salve, coffee beans, bath bombs — even beard oil. This motley collection shared a single star ingredient: CBD.
Produced by the cannabis plant, CBD is the straitlaced cousin of marijuanas more famous component — the THC that delivers a mind-swirling high. CBD, or cannabidiol, has no such intoxicating effects on the mind. Yet the molecule has captured peoples attention in a profound way, sold as a remedy for pain, anxiety, insomnia and other ailments — all without the high.
That neighborhood shop, CBD Scientific, is far from alone in its efforts to sell people on the benefits of CBD, which is found in both marijuana and hemp, two versions of the Cannabis sativa plant. CBD is popping up in products in pet stores, coffee shops and the health and beauty sections of mainstream grocery stores. Its even being brewed into beer. I left the shop with a $5 bottle of water infused with “5,000,000 nanograms” of CBD.
So far, messages of CBDs purported health benefits come from people trying to sell CBD products — not from scientists, says Margaret Haney, a neurobiologist who directs the Marijuana Research Laboratory at Columbia University. A gaping chasm separates the surging CBD market and the scientific evidence backing it. While there are reasons to be excited about CBD, the science just isnt there yet, Haney says.
U.S. sales of CBD-containing products are on the rise, and industry watchers expect a growing market in years to come. Epidiolex, an antiseizure drug made available in 2018, is the only prescription medication containing CBD. Sales figures beginning with 2018 are estimates.
U.S. CBD market growth and projections, 2014–2022
Source: New Frontier Data 2018, Hemp Business Journal
Scientists still dont know all of the targets CBD hits in the human body, nor what effects it may have, if any. With the exception of tests in people with rare forms of epilepsy, large studies that compare CBD with placebos in people are rare. Much of the existing research was done with cells in the lab or in lab animals, with results that dont necessarily translate to people.
And theres always the chance that for some people, CBDs magic is made not by the compound itself but by a powerful placebo effect; people who expect good outcomes are more likely to see benefits.
Researchers are stepping into the void, lured by promising early data. Small trials are under way looking at the effect of CBD on anxiety, pain, opioid addiction, depression and other health problems. National Institutes of Health funding for CBD studies went from zero in 2014 to an estimated $16 million in 2018.
“Were very interested in CBD,” says Susan Weiss, director of the Division of Extramural Research at the National Institute on Drug Abuse in Bethesda, Md. Still, she urges caution to people eager to try CBD. Because of lax oversight, theres no telling whats inside many of those tinctures, oils, rubs and foods for sale online and in stores. “A lot of the products that people are taking may not be what they think,” she says.
Despite the risks and warnings, it seems safe to say that the collective fascination with CBD isnt going to wear off anytime soon. “People think its great for everything,” says cognitive neuroscientist Kent Hutchison of the University of Colorado Boulder. That cant possibly be true, he says. “But I do think its going to be great for some things. We just need to figure out what those things are.”
Each morning, Samantha Montanaro of Portland, Ore., drops a CBD tincture under her tongue. “Im kind of testing out my own body with this,” she says. “Im finding that it really helps with anxiety and stress.”
Montanaro isnt alone; CBD testimonials are increasingly easy to find. In 2016, Montanaro, now 35, cofounded Tokeativity, a global cannabis community for women. Back then, “CBD wasnt even a thing,” she says. But the first sparks of the CBD movement caught fire fast. “Its been pretty crazy to watch how things have evolved,” she says. Some bullish analysts predict that the CBD market in the United States will balloon from hundreds of millions of dollars in 2018 to almost $20 billion by 2022.
Ziva Cooper directs UCLAs Cannabis Research Initiative and fields a lot of questions about CBD. Her answers invariably disappoint. “When I tell [people] we dont have very much evidence in people, theyre actually surprised,” she says. When it comes to CBDs benefits, “theres actually very little out there to hang our hats on.”
The one exception is for rare forms of childhood epilepsy. Neurologist Elizabeth Thiele of Massachusetts General Hospital in Boston had a young patient who was having over 100 seizures a day. After other treatments had failed, the boys parents began searching for a source of CBD oil, which they desperately wanted to try after learning about promising early results in animals. The family flew to England, so the boy could try the CBD formulation made by GW Pharmaceuticals. The childs results, Thiele says, were remarkable. After a week of CBD, his daily seizures had fallen to single digits.
That result ultimately led to clinical trials, one of which included 171 people, mostly children, with Lennox-Gastaut syndrome, a rare and severe seizure disorder. In addition to their normal medication, half of the participants got doses of CBD that were rigorously tested and standardized by the drugs maker. The other half received their regular treatment plus a placebo. After 14 weeks, the people taking CBD saw a median drop in monthly seizure frequency of about 44 percent; seizures in people who took the placebo dropped almost 22 percent. Thiele and her colleagues published those results in March 2018 in the Lancet.
Side effects were manageable, the researchers found. Diarrhea, sleepiness, poor appetite and vomiting were more likely to occur in the people who took CBD than in those who got the placebo. Along with results from several other trials, those data were strong enough to prompt the U.S. Food and Drug Administration to approve the CBD drug, called Epidiolex, last June.
In people with severe forms of epilepsy, CBD plus normal treatment (dark green bar) curbed seizures to a greater extent than did a placebo coupled with normal treatment (light green bar), one trial showed.
Reduction in seizure frequency during treatment
Source: E.A. Thiele et al/The Lancet 2018
Despite rigorous testing of Epidiolex, big gaps in knowledge on how the drug works in epilepsy remain. Researchers dont know how CBD tames seizures. Because the molecule comes from cannabis, the early assumption was that CBD latches onto the same chemical receptors that THC connects to, one primarily in the brain and one mainly on immune cells. It turns out, however, that CBD doesnt seem to hit either of those receptors.
Instead, studies in rats and mice point to two different targets. One, called TRPV1, is known to play a role in pain sensation and maybe epilepsy, too. The other, called GPR55, might change the activity level of nerve cells in the brain, a feat that may be behind CBDs antiseizure power.
Scientists also dont know whether CBD keeps working year after year. For some of Thieles patients, CBD seems to still be effective after five years of taking the drug, even allowing them to taper off some of their other medications, she says. But data from 92 other patients, presented in December at the American Epilepsy Societys annual meeting, suggest that CBDs benefits can start to fade after about seven months on the drug. About a third of the people in the study needed a dose increase after their CBD doses became less effective, researchers from Tel Aviv Sourasky Medical Center reported.
Research on CBD and other ailments lags way behind the epilepsy work. Early experiments, mostly on lab animals but some in small numbers of people, suggest that CBD might fight anxiety, ease schizophrenia symptoms and address pain.
One example: Healthy men who took CBD before a stressful public speaking task were calmer than those who took a placebo, researchers reported in October in the Brazilian Journal of Psychiatry. But only the 15 men who received doses of 300 milligrams were more relaxed. The 27 who took less or more CBD didnt see benefits. Other types of studies with people, and studies of mice and rats, have turned up antianxiety effects, too. But most of these studies looked at single doses of CBD, not consistent use.
Early evidence of CBDs promise against schizophrenia comes from a trial of 88 people with the disorder. After six weeks, people who had received a big daily dose of CBD (1,000 milligrams a day) in addition to their normal medication had more improvements in certain symptoms when compared with people who received a placebo. Those results hint that CBD might be a new type of drug for schizophrenia, researchers wrote in March 2018 in the American Journal of Psychiatry.
Studies in lab animals suggest that CBD may help relieve chronic pain. A study appearing in 2017 in Pain found that CBD could block osteoarthritis pain and nerve damage in rats. Hard data for humans are harder to find, but anecdotes abound. Pain clinician Kimberly Mauer of Oregon Health & Science University in Portland and colleagues at the OHSU Comprehensive Pain Center have seen an uptick in patients who say theyre taking CBD. Their experiences are mixed, she says: “About half the patients say they get some benefit, and about half say they didnt notice anything.”
No easy access[hhmc]
To answer the many outstanding questions about CBDs effects, scientists need access to the compound. But a complex web of U.S. regulations makes that difficult. CBD is subject to rules from both the FDA and the U.S. Drug Enforcement Administration. CBD produced by the marijuana plant remains on the DEAs list of the most restrictive class of drugs, Schedule 1, alongside LSD, ecstasy and other drugs deemed to have no accepted medical use and high potential for abuse. Access restrictions on industrial hemp, and by extension, the CBD that comes from hemp, were eliminated in the 2018 Farm Bill, signed into law in December. However, regardless of its provenance, CBD is still subject to FDA regulations, as well as any regulations imposed by states.
A tale of two plants[hhmc]
Walther Otto Müller/Wikimedia Commons
“As easy as its gotten for the average person to go legally to buy recreational marijuana and consume it in many states, its gotten harder for scientists,” says Haney at Columbia. One of the few approved sources of CBD is a government-sanctioned cannabis facility at the University of Mississippi in Oxford. After she gets the CBD she needs for her studies, Haney is required to meticulously account for every milligram. “I have a gun safe in a locked room that I get into with my fingerprints to store both cannabidiol and marijuana.”
With those restrictions, many scientists just cant do the studies they want, Hutchison says. “The whole thing is a little bit crazy. People can sell it everywhere, but its very difficult for scientists to study its effects in humans.”
Hutchison and colleagues have figured out a legal work-around that doesnt require researchers to obtain supplies of CBD. The team is avoiding the government-grown cannabis, which can be quite different from the products in circulation, by testing the effects of the cannabis products that people are actually using. To do this, the researchers created a mobile pharmacology lab they call the CannaVan. The tricked-out Dodge contains equipment to study people after theyve taken a product containing CBD (or THC) that they bought themselves. The researchers are currently collecting data on CBDs effects on anxiety and pain.
FDA rules say that CBD cannot be legally added to food and sold across state lines, sold as a dietary supplement or marketed with claims of treating diseases. But aside from sending some warning letters, the FDA has, so far, let the marketplace run uninhibited. (Some local health authorities, however, are beginning to flex their might, warning restaurants in New York City, for instance, to take CBD off the menu.)
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