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A new study shows that an FDA-approved, pharmaceutical-grade formulation of CBD has an antiviral effect in human lung cells and mice, and shows a significant negative association with COVID infection in human patients. 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 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

Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data

An interdisciplinary team of researchers from the University of Chicago has found evidence that cannabidiol (CBD), a product of the cannabis plant, can inhibit infection by SARS-CoV-2 in human cells and in mice.

The study, published on January 20, 2022, in Science Advances, found CBD showed a significant negative association with SARS-CoV-2 positive tests in a national sample of medical records of patients taking the FDA-approved drug for treating epilepsy. The researchers now say that clinical trials should be done to determine whether CBD could eventually be used as a preventative or early treatment for COVID-19. They caution, however, that the COVID-blocking effects of CBD come only from a high purity, specially formulated dose taken in specific situations. The study’s findings do not suggest that consuming commercially available products with CBD additives that vary in potency and quality can prevent COVID-19.

Scientists have been looking for new therapies for people infected by the coronavirus and emerging variants, especially those who lack access to vaccines, as the pandemic continues across the country and world and as breakthrough infections become more common.

CBD: An unexpected avenue for fighting COVID-19

The idea to test CBD as a potential COVID-19 therapeutic was serendipitous. “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.’ Surprisingly, it directly inhibited viral replication in lung cells,” said Marsha Rosner, PhD, Charles B. Huggins Professor in the Ben May Department of Cancer Research and a senior author of the study.

To see this effect, the researchers first treated human lung cells with a non-toxic dose of CBD for two hours before exposing the cells to SARS-CoV-2 and monitoring them for the virus and the viral spike protein. They found that, above a certain threshold concentration, CBD inhibited the virus’ ability to replicate. 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.

CBD did not affect the ability of SARS-CoV-2 to enter the cell. Instead, CBD was effective at blocking replication early in the infection cycle and six hours after the virus had already infected the cell.

Like all viruses, SARS-CoV-2 affects the host cell by hijacking its gene expression machinery to produce more copies of itself and its viral proteins. This effect can be observed by tracking virus-induced changes in cellular RNAs. High concentrations of CBD almost completely eradicated the expression of viral RNAs. It was a completely unexpected result.

“We just wanted to know if CBD would affect the immune system,” Rosner said. “No one in their right mind would have ever thought that it blocked viral replication, but that’s what it did.”

The researchers showed that the mechanism by which CBD blocks SARS-CoV-2 replication involves CBD activation of one of the host cell stress responses and generation of interferons, an antiviral cell protein.

Real world data: Patients taking CBD test positive for COVID-19 at lower rates

The researchers wanted scientific data to show that CBD prevents viral replication in live animals. The team showed pretreatment with CBD for one week prior to infection with SARS-CoV-2 suppressed infection both in the lung and the nasal passages of mice. “These results provide major support for a clinical trial of CBD in humans,” said Rosner.

And the success of CBD wasn’t limited to the laboratory: An 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 potential for CBD to treat patients recently exposed to or infected by SARS-CoV-2 does not precede the first lines of defense against COVID-19, which are to get vaccinated and follow existing public health guidelines for masking in indoor spaces and social distancing. But the published results offer a potential new therapeutic, something still needed as the pandemic rages on.

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“A clinical trial is necessary to determine whether CBD is really effective at preventing or suppressing SARS-CoV-2 infection, but we think this may have potential as a prophylactic treatment,” said Rosner. “Maybe you’re in a hot spot or you think you might have been exposed or you’ve just tested positive — that’s where we think CBD might have an effect.”

Not your dispensary’s CBD

The research team emphasized 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 plants, did not have the same power. In fact, combining CBD with equal amounts of THC actually reduced the efficacy of CBD.

“Going to your corner bakery and buying some CBD muffins or gummy bears probably won’t do anything,” said Rosner. “The commercially available CBD powder we looked at, which was off the shelf and something you could order online, was sometimes surprisingly of high purity but also of inconsistent quality. It is also hard to get into an oral solution that can be absorbed without the special, FDA-approved formulation,” Rosner said.

Furthermore, CBD use is not without potential risks. It appears to be extremely safe when consumed in food or drink, but methods of use such as vaping can have negative side effects, including potential damage to the heart and lungs. It’s also not well studied in certain populations, such as pregnant people, and so should be used only under the supervision of a physician and with caution.

While the study’s results are exciting, additional study is needed to determine the precise dosing of CBD that is effective at preventing SARS-CoV-2 infection in humans as well as its safety profile and any potential side effects.

“We are very eager to see some clinical trials on this subject get off the ground,” Rosner said. “Especially as we are seeing that the pandemic is still nowhere near the end — determining whether this generally safe, well-tolerated, and non-psychoactive cannabinoid might have anti-viral effects against COVID-19 is of critical importance.”

Rosner was also pleased that this research project was a case study in the power of scientific collaboration by bringing together a highly interdisciplinary group of researchers. Senior authors listed on the paper came from three different research universities and from departments as diverse as microbiology, molecular engineering, cancer biology and chemistry.

“This was truly a team-science effort, and that’s something that really excites me,” said Rosner. “From clinicians to David Meltzer’s group who did the patient analysis to virologists like Glenn Randall, and it goes on and on. This is the way science should be carried out.”

The study, “Cannabidiol Inhibits SARS-CoV-2 Replication through Induction of the Host ER Stress and Innate Immune Responses,” was supported by a BIG Vision grant from the University of Chicago, the National Institutes of Health (R01 GM121735, R01 CA184494, R01 AI137514, R01 AI127518, R01 AI134980, R01 CA219815, R35 GM119840, P30 CA014599), and the Harry B. and Leona M Helmsley Charitable Trust. Additional authors include Long Chi Nguyen, Dongbo Yang, Thomas J. Best, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Lydia Robinson-Mailman, Andrea Valdespino, Letícia Stock, Eva Suárez, Krysten A. Jones, Saara-Anne Azizi, James Michael Millis, Bryan C. Dickinson, Savaş Tay, Scott A. Oakes, and David O. Meltzer of the University of Chicago; Vlad Nicolaescu, Haley Gula, and Glenn Randall of UChicago and Argonne National Laboratory; Divayasha Saxena, Jon D. Gabbard, Jennifer K. Demarco, William E. Severson, Charles D. Anderson, and Kenneth E. Palmer of the University of Louisville; Shao-Nong Chen, Takashi Ohtsuki, John Brent Friesen, and Guido F. Pauli of the University of Illinois at Chicago; and the National COVID Cohort Collaborative Consortium.

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).

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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.”

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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.

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.

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