Can CBD fight COVID-19? A new study published in Science Advances reports evidence that cannabidiol, a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in It’s too early to tell whether CBD helps against Covid-19 — but researchers worry that won’t stop CBD makers.
Can CBD fight COVID-19?
A new study published in Science Advances reports evidence that cannabidiol, a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in mice. SARS-CoV-2 is the virus that causes COVID-19.
The study, co-authored by researchers from the University of Illinois Chicago and the University of Chicago, found that pharmaceutical-grade cannabidiol showed a significant negative association with SARS-CoV-2 replication.
A new study co-authored by UIC researchers reports evidence that pure, pharmaceutical-grade CBD can inhibit SARS-CoV-2 replication. (Photo: Elsa Olofsson/Unsplash).
To study the effect of cannabidiol, commonly called CBD, the researchers first treated human lung cells with a non-toxic dose of CBD for two hours. Then they exposed the cells to SARS-CoV-2 and monitored them for the virus and the viral spike protein, which binds to human cells. While CBD did not affect the ability of SARS-CoV-2 to enter cells, the researchers observed that when above a certain threshold concentration, CBD inhibited the virus’s ability to replicate early in the infection cycle — approximately six hours after the virus had already infected the cell. Further investigation found that CBD had the same effect in two other types of cells and for three variants of SARS-CoV-2 in addition to the original strain.
The researchers also studied the effect of CBD on viral replication in animals. The team showed that pretreatment with CBD for one week prior to infection suppressed infection both in the lung and the nasal passages of mice.
Guido Pauli, the Norman R. Farnsworth professor of pharmacognosy and director of the Pharmacognosy Institute at the UIC College of Pharmacy, and his team were responsible for ensuring the integrity and purity of CBD and related products, enabling them to determine the compounds with valid therapeutic potential and identify the lead compound tested in the experiments.
“To truly understand the medicinal potential of a natural product, we not only need to verify the active compound and how it is derived from the plant source but also that we can extract and prepare the compound in a reliable way,” Pauli said. “When it comes to something like CBD, this is even trickier because of the widespread availability of products whose quality is essentially unregulated and practically impossible to determine without knowledge of and access to reliable laboratory testing.”
Pauli and his team have extensive experience studying biologically active natural products and their therapeutic potential.
A recent study led by Pauli on the essential medicinal chemistry of cannabidiol provided evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims generally lack a rigorous scientific foundation. In another previous publication, the UIC team reported a process to analyze, characterize and, if possible, prepare pure CBD compounds from the range of widely available products called CBD Oils, which Pauli points out may contain many other things than the declared cannabinoid.
“The products that are commercially or readily available with CBD labels or ingredients are not nearly regulated in the same way as medical drugs,” Pauli said. “Buyers can really have no idea what is in those products, which may or may not contain CBD, and if they do, CBD might be present in largely different amounts and along with many other ingredients.
“It’s critical to understand that the CBD materials evaluated in this study were high-quality, pharmaceutical-grade, high-purity CBD,” he said.
The success of CBD as published in the Science Advances publication wasn’t limited to the laboratory. A retrospective analysis of 1,212 patients from the National COVID Cohort Collaborative revealed that patients taking a medically prescribed oral solution of CBD for the treatment of epilepsy tested positive for COVID-19 at significantly lower rates than a sample of matched patients from similar demographic backgrounds who were not taking CBD.
The researchers reported that the COVID-blocking effects of CBD were confined strictly to high purity, high concentrations of CBD. Closely related cannabinoids such as CBDA, CBDV and THC, the psychoactive element enriched in marijuana (not hemp) plants, did not have the same power. Combining pure CBD with equal amounts of THC in fact drastically reduced the efficacy of CBD.
“While I believe strongly in the therapeutic potential of many natural products and am confident the results of this study provide a promising avenue for further research into CBD to mitigate the harm of COVID-19, the last thing I want to see is people running to a local dispensary. Until we have obtained clinical evidence, it is premature and will likely have no benefit, or could even potentially cause harm in some cases,” Pauli said.
The idea to test CBD as a potential COVID-19 therapeutic was serendipitous, according to a news release on the study from the University of Chicago.
“CBD has anti-inflammatory effects, so we thought that maybe it would stop the second phase of COVID infection involving the immune system, the so-called ‘cytokine storm,’” said Marsha Rosner, professor of cancer research at the University of Chicago and a senior author of the study. “We just wanted to know if CBD would affect the immune system. No one in their right mind would have ever thought that it blocked viral replication, but that’s what it did.”
The study, “Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses,” was supported by grants from the National Institutes of Health (R01 GM121735, R01 CA184494, R01 AI137514, R01 AI127518, R01 AI134980, R01 CA219815, R35 GM119840, P30 CA014599), the University of Chicago, and the Harry B. and Leona M Helmsley Charitable Trust.
Additional authors include Shao-Nong Chen, Takashi Ohtsuki and John Brent Friesen of UIC; Long Chi Nguyen, Dongbo Yang, Thomas Best, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Lydia Robinson-Mailman, Andrea Valdespino, Letícia Stock, Eva Suárez, Krysten Jones, Saara-Anne Azizi, James Michael Millis, Bryan Dickinson, Savas Tay, Scott Oakes, and David Meltzer of the University of Chicago; Vlad Nicolaescu, Haley Gula, and Glenn Randall of the University of Chicago and Argonne National Laboratory; Divayasha Saxena, Jon Gabbard, Jennifer Demarco, William Severson, Charles Anderson, and Kenneth Palmer of the University of Louisville; and the National COVID Cohort Collaborative Consortium.
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.”
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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.”
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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.
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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.
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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.
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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.