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It’s too early to tell whether CBD helps against Covid-19 — but researchers worry that won’t stop CBD makers. Compounds in cannabis can prevent infection from the virus that causes Covid-19 by blocking its entry into cells, according to a study published this week by researchers affiliated with Oregon State University.

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.

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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.

Study Finds Cannabis Compounds Prevent Infection By Covid-19 Virus

Compounds in cannabis can prevent infection from the virus that causes Covid-19 by blocking its entry into cells, according to a study published this week by researchers affiliated with Oregon State University. A report on the research, “Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants,” was published online on Monday by the Journal of Natural Products.

The researchers found that two cannabinoid acids commonly found in hemp varietals of cannabis, cannabigerolic acid, or CBGA, and cannabidiolic acid, also known as CBDA, can bind to the spike protein of SARS-CoV-2, the virus that causes Covid-19. By binding to the spike protein, the compounds can prevent the virus from entering cells and causing infection, potentially offering new avenues to prevent and treat the disease.

Compounds in cannabis can prevent infection by the virus that causes Covid-19, according to research . [+] published this week.

“Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2,” the researchers wrote in an abstract of the study.

The study was led by Richard van Breemen, a researcher with Oregon State’s Global Hemp Innovation Center in the College of Pharmacy and Linus Pauling Institute, in collaboration with scientists at the Oregon Health & Science University. Van Breeman said that the cannabinoids studied are common and readily available.

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“These cannabinoid acids are abundant in hemp and in many hemp extracts,” van Breemen said, as quoted by local media. “They are not controlled substances like THC, the psychoactive ingredient in marijuana, and have a good safety profile in humans.”

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Cannabinoids Effective Against New Variants

Van Breemen added that CBDA and CBGA blocked the action of emerging variants of the virus that causes Covid-19, saying that “our research showed the hemp compounds were equally effective against variants of SARS-CoV-2, including variant B.1.1.7, which was first detected in the United Kingdom, and variant B.1.351, first detected in South Africa.”

CBGA and CBDA prevented infection from the virus that causes Covid-19 by binding to its . [+] characteristic spike protein.

The spike protein is the same part of the virus target by Covid-19 vaccines and antibody therapies. In addition to the spike protein, SARS-CoV-2 has three more structural proteins as well as 16 nonstructural proteins and several compounds van Breemen characterized as “accessory” proteins, all of which are potential targets for drugs developed to prevent Covid-19.

“Any part of the infection and replication cycle is a potential target for antiviral intervention, and the connection of the spike protein’s receptor binding domain to the human cell surface receptor ACE2 is a critical step in that cycle,” van Breeman said. “That means cell entry inhibitors, like the acids from hemp, could be used to prevent SARS-CoV-2 infection and also to shorten infections by preventing virus particles from infecting human cells. They bind to the spike proteins so those proteins can’t bind to the ACE2 enzyme, which is abundant on the outer membrane of endothelial cells in the lungs and other organs.”

Although further research is needed, van Breemen noted that study shows the cannabinoids could be developed into drugs to prevent or treat Covid-19.

“These compounds can be taken orally and have a long history of safe use in humans,” van Breemen noted. “They have the potential to prevent as well as treat infection by SARS-CoV-2. CBDA and CBGA are produced by the hemp plant as precursors to CBD and CBG, which are familiar to many consumers. However, they are different from the acids and are not contained in hemp products.”

Van Breeman also noted that the research showed the cannabinoids were effective against new variants of the virus, which he said are “one of the primary concerns” in the pandemic for health officials and clinicians.

“These variants are well known for evading antibodies against early lineage SARS-CoV-2, which is obviously concerning given that current vaccination strategies rely on the early lineage spike protein as an antigen,” said van Breemen. “Our data show CBDA and CBGA are effective against the two variants we looked at, and we hope that trend will extend to other existing and future variants.”

The researcher added that “resistant variants could still arise amid widespread use of cannabinoids but that the combination of vaccination and CBDA/CBGA treatment should make for a much more challenging environment for SARS-CoV-2.”

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