Early Studies Suggest CBD May Help Prevent COVID-19 Medical formulations of the compound cannabidiol — known as CBD — have shown promise as a way to prevent COVID-19. Medical formulations of It’s too early to tell whether CBD helps against Covid-19 — but researchers worry that won’t stop CBD makers. David Aronoff, MD, discusses an early study on CBD and on how to address interested patients
Early Studies Suggest CBD May Help Prevent COVID-19
Medical formulations of the compound cannabidiol — known as CBD — have shown promise as a way to prevent COVID-19.
Medical formulations of the compound cannabidiol — known as CBD — have shown promise as a way to prevent COVID-19.
What you need to know
Cannabidiol (CBD) is a cannabis compound with some medicinal properties. Unlike tetrahydrocannabinol (THC) — the main psychoactive component of cannabis — CBD does not produce a high or euphoria. The U.S. Food and Drug Administration (FDA) has approved one CBD-based medication to treat seizure disorders; other medications are in the development and testing pipeline.
Now some early studies show that CBD could help block infection with SARS-CoV-2, the virus that causes COVID-19.
What did the researchers do?
In a series of studies supported by the National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute (NCI), and the National Center for Advancing Translational Sciences, researchers tested the effects of CBD and other cannabis compounds on SARS-CoV-2. They looked at interactions between CBD and the virus in human lung cells and in mice. They also analyzed data from the National COVID Cohort Collaborative’s health records of volunteers who had been prescribed the CBD-based medication to help prevent seizures.
What did they learn?
In both the laboratory studies and the health records analyses, CBD seemed to have a protective effect against SARS-CoV-2. When the virus was introduced to human lung cells treated with CBD, it could not replicate and take hold as it usually does. Mice that were given therapeutic doses of CBD before being exposed to the virus were much less likely to develop COVID-19 than mice in the control group. And human patients who took the CBD-based medication were less likely to report a COVID-19 diagnosis than others, including people who had the same seizure disorders but had not been prescribed that medication.
Interestingly, out of more than 100 compounds in cannabis, only CBD showed this protective effect. In fact, when CBD was combined with THC, its ability to protect decreased.
What does this mean?
More research, including clinical trials, is needed, but these studies suggest that CBD might be a useful way of preventing COVID-19 in the future. The researchers caution that CBD is not a replacement for vaccination, masking, and social distancing. If anything, they write, CBD would be used along with these measures to prevent breakthrough infections.
The researchers also emphasize that the CBD used in their studies is different from the nonmedical products consumers might be familiar with. There is no evidence that taking over-the-counter CBD products can prevent or treat COVID-19 infection.
Where can I go to learn more?
NCI provides patient-friendly information about cannabis and its compounds.
The National Center for Complementary and Integrative Health has more information about cannabis and CBD.
N3C is a partnership among several NIH Institutes and Centers that aims to use COVID-19 clinical data to answer critical research questions.
It’s too early to tell whether CBD helps against Covid-19 — but researchers worry that won’t stop CBD makers
T he scientists stressed the caveats that early-stage research demands: the compounds they had studied showed hints — in cells in lab dishes and in animals — of being able to combat the coronavirus. Definite answers could only come from clinical trials.
But the compounds were CBD and other marijuana and hemp derivatives, so the news took off. Kimmel and Colbert cracked jokes. The studies received coverage in outlets from Fox News to The Daily Beast.
The latest hubbub is an example of both the promise of cannabinoids — components of cannabis — as potential therapies, but also the hype around them, which can far outpace the evidence that they work. It’s left researchers and consumer advocates scrambling to warn people that patients shouldn’t be turning to over-the-counter products or recreational marijuana in hopes that it might protect them from Covid-19.
“We don’t want people running out taking random cannabinoids,” said Marsha Rosner of the University of Chicago, the senior author of one of the new studies.
The research also presents a new challenge for the Food and Drug Administration, which is already struggling to police the rapidly growing CBD market. While the agency has said CBD makers can’t market their products as medical treatments without conducting a clinical trial and submitting an application to the agency, few companies have actually invested in conducting those trials. Instead, companies have tried to tiptoe around the FDA rules by selling their products as dietary supplements and making only modest claims. Experts fear that the FDA’s job will only get harder with the increased hype around cannabinoids and Covid-19.
“These kinds of studies are what these companies look for to promote their products — that’s the scary part,” said Jeanette Contreras, director of health policy at the National Consumers League, which runs a campaign called Consumers for Safe CBD. “This gives them more fuel to make false claims about their products.”
Related: The FDA is finalizing its long-awaited rules for CBD
R osner and her team were initially skeptical that CBD could have any potential effect for Covid-19. They thought that if there was going to be any benefit, it might be in the late-stage illness that occurs when the immune response to the virus goes into hyperdrive.
But then they found something that surprised them: While CBD couldn’t block the virus from entering human epithelial cells in lab dishes, it prevented the pathogen from hijacking the cell’s internal Xerox machines to make copies of itself. It also lowered viral levels in infected mice.
Rosner and her team’s paper was published in Science Advances this month, soon after researchers in Oregon reported in the Journal of Natural Products that two chemicals found in hemp, CBGA and CBDA, could bind to the virus’ spike protein and thus prevent it from infecting cells in lab dishes.
Together, the two studies earned attention for the suggestion that cannabinoids might have a role to play in the pandemic.
But since the work was published, Rosner has been trying to inject caveats and nuances into the discussion around CBD for Covid.
As she emphasizes: experiments in mice and cells in lab dishes regularly seem like breakthroughs, whether for Covid-19 or just about any other ailment. But only rarely do they go on to demonstrate any actual effectiveness in human trials.
Outside researchers also noted that the two papers reported sometimes opposing results for how cannabinoids interacted with the coronavirus, indicating that any potential effect needs to be further studied.
“These are the seeds of our knowledge related to how cannabinoids might interact with the SARS-Cov-2 virus,” said Ziva Cooper, the director of the UCLA Cannabis Research Initiative. “We have a long way to go.”
Related: A spate of new class-action lawsuits threaten the CBD industry. Will they force Washington to act?
T he new studies are adding to the FDA’s existing CBD headache, too.
The agency has already grappled with companies trying to use early research into CBD and Covid-19 to promote their products — it has sent 13 official warning letters demanding that companies stop selling their CBD products as Covid-19 treatments.
Some of those companies did not explicitly call their products cures, but instead included outside research on their websites that could lead consumers to believe CBD was a proven treatment for Covid-19, STAT found when it reviewed the FDA’s warning letters. Other companies explicitly noted that their product was not a treatment for Covid-19 but suggested, for example, that “ the best thing you can do is boost your immune system.”
This has been a long-running issue with CBD, which the FDA regulates the same way it does other prescription drugs. That means anything with CBD in it must go through the agency’s rigorous approval process if companies want to suggest it can treat or cure anything at all.
Few companies have been willing to invest the time and effort needed to actually get a CBD drug through the regulatory odyssey. Instead, most market their products as dietary supplements in hopes that the FDA will not crack down on their individual products.
Related: The company behind the first-ever CBD-based drug is now eyeing everything from multiple sclerosis to autism
Research is hard for other reasons, too. Just a few years ago, researching cannabidiol was heavily restricted because of marijauna’s legal status, and the trials are still hard to conduct — one researcher called the system a “nightmare.”
That means there’s hardly any infrastructure or investment into actually testing whether CBD has an impact on Covid-19.
In fact, there’s still not much late-stage clinical research into whether CBD really does much of anything at all.
“The status quo is challenging,” said Lowell Schiller, the former co-lead of the FDA’s CBD working group. “When we see potentially promising research coming out of the laboratory setting, where are the dollars coming from to do the kind of rigorous clinical research that we need to genuinely understand whether there’s a there there ?”
It’s an open question whether new trials looking at cannabinoids and Covid will take off. Scientists have hypothesized that CBD or other cannabinoids might have some role to play against Covid-19 for much of the pandemic, but a STAT review of clinicaltrials.gov identified just seven trials that have tested CBD as a therapy for Covid-19, the majority of which are early-stage studies that would not produce the type of results necessary to conclude whether CBD can help combat the pandemic.
Rosner said she and her colleagues have been in touch with various companies about clinical trials, but so far, nothing’s set up. “Our hope is we can get some traction in the near future,” she said.
Related: These four companies are betting big on CBD-based prescription drugs
Richard van Breemen, a professor of medicinal chemistry at Oregon State University and one of the scientists involved with the other paper, told the Boston Globe this month that he expected data from clinical trials later this year. He did not respond to a question from STAT about whether clinical trials based on his team’s research had started or when they might.
Not all clinical trials are created equally, either — a fact that has dogged scientists’ efforts to test potential Covid-19 treatments. Going back to the heady days of hydroxychloroquine mania, dozens of trials of different treatments were launched based on preclinical hope, but they were ultimately too small or too poorly designed to come up with definite answers. The pileup of unhelpful U.S. clinical trials stands in stark contrast to something like the Recovery trial out of the United Kingdom, where a cohesive strategy and a national health system led to clear findings about treatments like dexamethasone (which worked) and convalescent plasma (which didn’t).
“It’s not just, is there a clinical trial, but what kind of clinical trial?” Rosner said, adding that her team was hoping to conduct a rigorous trial.
Trending Now: Pfizer isn’t sharing Covid vaccines with researchers for next-gen studies
In the meantime: Rosner is urging consumers not to go buy CBD to try to prevent Covid-19. For one, it’s not clear the products available at convenience stories contain pure CBD, or at what levels. The clinical trial Rosner envisions would test a pharmaceutical-grade CBD — something like the FDA-approved Epidiolex, an epilepsy treatment.
There’s another reason why people shouldn’t smoke marijuana or pop an edible and think it might be helping protect them from Covid-19, Rosner added: While her team reported an effect from CBD, the scientists found that the added presence of THC — the component of marijuana that makes people high — counteracted whatever benefits CBD may provide.
“The last thing we would like to see is for someone to say, ‘I’m going to go out and take CBD,’ and say, ‘I’m not going to get vaccinated, I’m not going to get boosted, I’m going to take off my mask,’” she said.
So, Your Patient Just Asked About CBD for COVID-19?
— David Aronoff, MD, discusses an early study on CBD and on how to address interested patients
by Emily Hutto, Associate Video Producer January 28, 2022
In this video, David Aronoff, MD, chair of the department of medicine at Indiana University School of Medicine in Indianapolis, discusses a recent study testing cannabidiol (CBD) against COVID-19 in the lab and in mice, and how to guide patients seeking treatment for COVID-19.
The following is a transcript of his remarks:
If a patient were to come to me and ask about the use of CBD oil to prevent COVID-19 or reduce the severity of it, I would say that right now, that approach is not ready for prime time. There are other, better ways that we know are safe and very effective to prevent COVID-19 and reduce the severity if someone gets ill. So wear your mask, socially distance, get vaccinated, and if you get symptomatically ill with COVID, let a healthcare professional know, because you may be eligible for things like monoclonal antibodies or new medications like Paxlovid [nirmatrelvir/ritonavir] or repurposed medicines like fluvoxamine [Luvox]. But it’s really important to engage with a licensed healthcare professional if you’re sick with COVID-19.
These investigators thought that there may be some anti-inflammatory effects of CBD, and that might be useful to suppress some of the inflammation that can occur in patients who have COVID-19. But the investigators found a surprising result, which is that CBD and one of its active metabolites didn’t really have too much of an effect on the inflammatory response of the epithelial cells they were studying. But rather, and curiously, the CBD seemed to block the replication of the SARS CoV-2 virus in the respiratory epithelial cells.
This really led the investigators to dig deeper into trying to understand whether the effect they were seeing was specific to CBD or could be found in other compounds that may be also identified in marijuana and to try to drill down on mechanisms through which CBD could be limiting SARS CoV-2 replications in epithelial cells.
And finally, based on what they found in vitro, they wanted to know if there were any correlates of this compound being used in humans that may show some promise for reducing the risk of COVID-19 and even went as far as doing an interventional study in mice to look at the impact of CBD on reducing the severity of SARS COVID-2 infection in a mouse model.
While this study is really interesting and promising, we don’t yet have data in humans that show that we can use CBD oil in therapeutic ways to prevent COVID-19 or reduce the severity of COVID-19. And really what we need is an actual randomized placebo-controlled, double-blind study, which is now regularly being done to look at therapeutic and preventive strategies for COVID-19. Right now, the best we can say about CBD oil is that it’s a promising idea. But until we have properly controlled studies, we don’t actually know how effective or not this is in humans.
Even the human component of the study that was just published, although it was retrospective, which has its limitations, it was looking at essentially medical-grade CBD oil used in the treatment of people who have severe seizure disorders. So we really don’t know how commercially-available, easy-to-get CBD preparations might perform in protecting people from COVID-19.
Emily Hutto is an Associate Video Producer & Editor for MedPage Today. She is based in Manhattan.