The CBD boom is well ahead of science

A few months ago, a new showcase appeared in my small town of Oregon. His shelves were filled with tinctures, jars of balm, coffee beans, bath bombs and even beard oil. This motley collection shared a key ingredient: CBD.

Produced from the cannabis plant, CBD is the close cousin of the most famous component of marijuana – THC, which offers a vertiginous effect. CBD, or cannabidiol, has no intoxicating effects on the mind. Yet the molecule has captured people's attention in a profound way, sold as a cure for pain, anxiety, insomnia and other ailments – all without the slightest effect.

CBD Scientific, this neighborhood store, is far from the only one trying to sell to people the benefits of CBD, which is found in both marijuana and hemp, two versions of Cannabis sativa plant. CBD is appearing in pet foods, cafes and health and beauty facilities in major grocery stores. It is even brewed in beer. I left the shop with a $ 5 water bottle infused with "5,000,000 nanograms" of CBD.

Margaret Haney, a neurobiologist who runs the Marijuana Research Lab at Columbia University, says so far that the CBD's claimed health benefits come from people trying to sell CBD products. A gaping chasm separates the growing CBD market and the scientific evidence confirming it. While there is reason to be excited about the CBD, the science is not yet developed, says Haney.

Scientists still do not know all the targets affected by CBD in the human body, nor its possible effects. With the exception of tests in people with epilepsy, large studies comparing CBD to placebos are rare. Much of the existing research has been done with cells in the laboratory or in laboratory animals, with results that do not necessarily translate to humans.

And there is always a chance that for some people the magic of CBD does not come from the compound itself but from a strong placebo effect; people who expect good results are more likely to see benefits.

Researchers are entering the void, attracted by the first promising data. Small trials are underway on the effect of CBD on anxiety, pain, opioid addiction, depression, and other health issues. Funding for CBD studies by the National Institutes of Health increased from zero in 2014 to approximately $ 16 million in 2018.

"We are very interested in the CBD," said Susan Weiss, director of the extramural research division at the National Institute on Drug Abuse in Bethesda, Maryland. She nevertheless recommends caution to those wishing to try CBD. Due to lack of vigilance, there is no indication of most of these dyes, oils, gels and foods for sale online and in stores. "Many of the products that people take may not be what they think," she says.

Despite the risks and warnings, it seems reasonable to say that the collective fascination for the CBD will not fade away anytime soon. "People think it's good for everything," says Kent Hutchison, cognition neuroscientist at the University of Colorado Boulder. That can not be true, he says. "But I think it's going to be great for some things. We just need to understand what these things are. "

Mystery molecule

Every morning, Samantha Montanaro from Portland, Oregon, drops a tincture of CBD under her tongue. "I sort of test my own body with that," she says. "I find that it really helps with anxiety and stress."

Montanaro is not alone; CBD evidence is becoming easier to find. In 2016, Montanaro, now 35, co-founded Tokeativity, a global cannabis community for women. At the time, "the CBD was not even a thing," she says. But the first sparks of the CBD movement caught fire quickly. "It's pretty crazy to see how things have changed," she says. Some bull analysts predict that the CBD market in the United States will grow from hundreds of millions of dollars in 2018 to nearly 20 billion dollars in 2022.

Ziva Cooper leads the UCLA Cannabis Research Initiative and asks many questions about the CBD. His answers are always disappointing. "When I tell [people] we do not have a lot of evidence in people, they are actually surprised, "she says. Regarding the benefits of the CBD, "there is actually very little to keep our hat on".

The only exception is the rare forms of infantile epilepsy. The neurologist Elizabeth Thiele of the Massachusetts General Hospital in Boston had a young patient who had more than 100 seizures a day. After the failure of other treatments, the boy's parents started looking for a source of CBD oil, which they desperately wanted to try after learning the first promising results in animals. The family flew to England, so the boy could try the CBD formulation made by GW Pharmaceuticals. The results of the child, says Thiele, were remarkable. After a week of CDB, his daily crises had dropped to a single figure.

This result eventually led to clinical trials, one of which involved 171 people, mostly children, with Lennox-Gastaut syndrome, a rare and serious convulsive disorder. In addition to their usual medications, half of the participants received doses of CBD that were rigorously tested and standardized by the drug manufacturer. The other half received his regular treatment plus a placebo. After 14 weeks, people taking HBD found a median drop in monthly seizure frequency of about 44%; seizures among people who took the placebo fell by almost 22%. Thiele and his colleagues published these results in March 2018 in the journal Lancet.

The researchers found that the side effects were manageable. Diarrhea, drowsiness, lack of appetite, and vomiting were more likely to occur in people taking CBD than those who received placebo. In addition to the results of several other trials, these data were strong enough to prompt the US Food and Drug Administration to approve the CBD-based drug, Epidiolex, last June.

Despite rigorous testing on Epidiolex, there are still major gaps in knowledge about how the drug works in the treatment of epilepsy. Researchers do not know how the CBD tames crises. As the molecule originates from cannabis, the initial hypothesis was that CBD locks on the same chemical receptors as THC, one mainly in the brain and the other mainly on immune cells. It turns out, however, that the CBD does not seem to affect any of these receptors.

Instead, studies in rats and mice indicate two different targets. The first, called TRPV1, plays a role in the sensation of pain and perhaps also in epilepsy. The other, called GPR55, could alter the level of activity of nerve cells in the brain, which could explain the anti-epileptic power of CBD.

Scientists also do not know if the CBD continues to function year after year. For some Thiele patients, CBD still appears to be effective after five years of taking the drug, even allowing them to gradually reduce their other medications, she says. But data from another 92 patients, presented in December at the annual meeting of the American Epilepsy Society, suggests that the benefits of HBD may begin to fade after about seven months of treatment with this drug. About one-third of those participating in the study needed a dose increase after their doses of CBD became less effective, researchers at Sourasky Medical Center in Tel Aviv said.

Research on CBD and other ailments is well behind work on epilepsy. Early experiments, mostly on laboratory animals but in a small number of people, suggest that CBD could fight anxiety, relieve symptoms of schizophrenia and relieve pain.

One example: healthy men who took CBD before a stressful conversation were calmer than those who took a placebo, researchers reported in October Brazilian Journal of Psychiatry. But only the 15 men who received 300 mg doses were more relaxed. The 27 who took less or more CBD did not see any benefits. Other types of studies in human subjects and studies in mice and rats have also revealed anxiolytic effects. But most of these studies have focused on single doses of CBD, without routine use.

The first evidence of the CBD promise against schizophrenia comes from a trial of 88 people with the disease. After six weeks, people who received a large daily dose of CBD (1,000 milligrams a day) in addition to their usual medications had some improvement in symptoms compared to those receiving placebo. These findings suggest that CBD could be a new type of drug for schizophrenia, researchers wrote in March 2018 American Journal of Psychiatry.

Studies in laboratory animals suggest that CBD may help relieve chronic pain. A study published in 2017 in Pain showed that CBD could block the pain and nerve damage of osteoarthritis in rats. It is difficult to find reliable data for humans, but anecdotes abound. Kimberly Mauer, pain clinic clinician at Oregon Health & Science University in Portland, and her colleagues at the OHSU comprehensive pain center have seen a slight increase in the number of patients reporting taking CBD. Their experiences are mixed, she said: "About half of patients say they benefit, and about half said they did not notice anything."

No easy access

To answer the many outstanding questions about the effects of the CBD, scientists need access to the compound. But a complex network of US regulations makes it difficult. The CBD is subject to the rules of the FDA and the US Enforcement Drug Enforcement Administration. The CBD produced by the marijuana plant remains on the DEA's list of the most restrictive drug class, Schedule 1, alongside LSD, ecstasy and other drugs known to have no medical use accepted and a high potential for abuse. Restrictions on access to industrial hemp and, by extension, CBD from hemp were removed in the 2018 Farm Bill, which came into effect in December. However, regardless of where it comes from, the CBD is still subject to FDA regulations as well as all state-imposed regulations.

"As easy as the average person legally travels to buy recreational marijuana and consume it in many states, it's getting 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 getting the CBD she needs for her studies, Haney has to meticulously count each milligram. "I have a gun chest in a locked room in which I write with my fingerprints to store cannabidiol and marijuana."

With these restrictions, many scientists simply can not do the studies they want, says Hutchison. "All this is a little crazy. People can sell it everywhere, but it is very difficult for scientists to study its effects on humans. "

Hutchison and his colleagues have discovered a legal solution that does not require researchers to source CBD. The team avoids government-grown cannabis, which can be very different from the products in circulation, by testing the effects of the cannabis products actually used by people. To do this, the researchers created a mobile pharmacology lab called CannaVan. The invented Dodge contains equipment to study people after taking a product containing CBD (or THC) they bought themselves. Researchers are currently collecting data on the effects of CBD on anxiety and pain.

Beware of the buyer

The FDA rules state that CBD can not be added legally to food and sold across the borders of a state, sold as a dietary supplement or sold with disease treatment claims. But aside from sending warning letters, the FDA has so far let the market fend for itself. (Some local health authorities, however, are beginning to be flexible, warning New York restaurants, for example, not to use the CBD on the menu.)

All in all, no one really knows what's between bottles, drinks and coffee shops for sale. A study published in 2017 in JAMA gives an idea of ​​the problem. Researchers commissioned and tested 84 products sold online in 2016 as products containing CBD. Of these, only 26 were accurately labeled (containing CBD at less than 10% of the amount claimed); 36 products had more CBD than their labels say; and 22 products had less. The researchers also found THC in 18 of the 84 samples.

Sophie Cloyd is a 30-year-old director of CBD, Ablis of Bend, Oregon. She is pregnant too. I recently met her in a ski lodge, where she offered drinks and described dyes, oils and lotions. CBD, she says, helped her manage this pregnancy, her second. She was prescribed the anti-nausea drug Zofran early in her pregnancy, but "research on Zofran has made me more afraid than lack of research on CBD," she says.

Ablis, which makes soft drinks and other CBD-based products, is currently getting purified CBD from Colorado, says Cloyd. When the CBD arrives, the company sends it to an independent lab to confirm that it has the appropriate amount of CBD, pesticides, and THC. But not all CBD sellers are testing their products.

An unexpected dose of THC may not be enough to elevate the user, but it could still be a problem, as reported more and more reports. To relieve his pain caused by psoriatic arthritis, a school bus driver from Beaverton, Oregon, was taking a daily dose of CBD oil. In early 2018, he failed a periodic drug testing test with high levels of THC, which led him to lose his job, reported the Portland news channel KATU. Even in appearance, small amounts of THC can accumulate in the body during repeated use.

A product may contain even worse surprises. Between December 2017 and January 2018, for example, 52 people became ill in Utah with symptoms such as hallucinations, vomiting and seizures, after taking what they thought was a CBD. It turned out that the products, often labeled "Yolo CBD oil," contained a synthetic cannabinoid and poisoned them.

Even though product labels were always accurate, people have no idea of ​​the correct dose of CBD (assuming the right dose is effective). "You see it being marketed at doses like 10 milligrams," says Hutchison. "Well, 10 milligrams probably do not do anything." By comparison, people who participated in an Epidiolex study took 20 milligrams per kilogram of body weight. To reach this daily dose, I would need 254 bottles of CBD water of 5 million nanograms that I bought at a cost of $ 1,270.

Haney makes the same point: "You do not get anything that looks like an effective dose when you add CBD to your coffee, or you buy a mint containing a little CBD," she says.

CBD products are even less known as you rub on your skin. Scientists do not know that CBD in creams, oils and ointments is actually present in the body. "I'm not convinced that everything you scrub with CBD goes through," says Haney.

The problem lies in the fact that most uses of the CBD are not supported by science, says Haney. "I'm not against the CBD," she says. In fact, she is about to begin a study on CBD to treat nerve pain due to chemotherapy in cancer patients. "But I do not like the marketers determining what it's used for or not."

The hype is not new, says Mauer, OSHU's pain doctor. Consumers are trying many things before the science is definitive – keto diets, for example, or vitamin D supplements (SN: 2/2/19, p. 16). And even if it turns out that the chemical is not working, the placebo effect may be enough to reduce the symptoms.

So far, science on the CBD is not advanced enough to intervene in one way or another. But judging by the number of studies and clinical trials underway, this emerging field of research is growing rapidly, seeking to quickly bridge the gap between science and what people want to know.

This boom in research has its heart in Montanaro. Her message to the scientific community: "I would encourage curiosity," she says. "I'm not a doctor or a scientist, but I certainly know my own body," and she says the CBD is helping her. From his point of view, science is lagging behind.

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This story appears in the March 30, 2019 issue of Scientific news with the title, "The attractiveness of the CBD: people are looking for health benefits despite the lack of evidence."