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.
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.