The cannabis plant is so much more than something people ingest to make them feel. Rather, hemp contains myriad cannabinoids — some estimates put as many as 100 different cannabinoid compounds — and many non-cannabinoid chemicals as well. Now scientists are putting two of the most well-known cannabinoids, THC (tetrahydrocannabinol) and CBD (cannabidiol) to the test: could either compound offer a potential treatment for Covid-19?
What’s New – In a paper published this week in the journal Science Advances, researchers led by researchers from the University of Chicago show that CBD and one of its metabolites, 7-OH-CBD, SARS-CoV-2, the causative virus, prevents Covid-19, from infecting cells. In addition, the researchers also tested CBD and 7-OH-CBD to see if they could prevent Covid-19 infection in mice – and they do.
The metabolite 7-OH-CBD is of particular interest as this is a secondary chemical produced when CBD is broken down by the body. Also of note is the finding that THC taken with CBD interferes with the beneficial effects seen with CBD treatment alone.
“This essentially eliminates the possibility of marijuana serving as an effective source of antiviral CBD,” they write in the study.
But just as importantly, as the researchers write in the study, this is not a green light to start taking CBD gummies in hopes of preventing or curing a Covid-19 infection.
“We currently caution against the use of non-medical formulations, including edibles, inhalants, or topical agents, as preventive or treatment therapy,” the researchers write.
The study builds on work from a cell study published earlier this month that suggests two other cannabinoids, CBDA and CBGA, block certain variants of the SARS-CoV-2 virus from infecting cells by getting involved in a key step in the Infection intervene: the virus’ spike proteins ability to bind to the ACE2 receptor on the surface of cells.
Why it matters – This study is new evidence that cannabinoids may be an untapped source for treatments of Covid-19, but it also advances the still preliminary research by testing the hypothesis not only in cells but also in mice tests. Mouse models are often used as the first step in testing new drugs for human use.
Additionally, the new study offers an explanation as to why CBD can prevent an infection from spreading — it appears that after SARS-CoV-2 enters a cell, CBD impairs the virus’ ability to replicate, thereby preventing an infection from spreading with special needs. It also appears to alter the immune system’s inflammatory response. This is a different treatment tactic than preventing infection because it focuses on what happens after exposure.
“So far, only a few therapies have been identified that block SARS-CoV-2 replication and virus production,” the researchers write in the study.
“CBD acts early in the infection cycle, in a post-entry step,” they add.
In addition, CBD offers great potential as a treatment against emerging variants of the coronavirus, the researchers argue, because it prevents replication after SARS-CoV-2 enters a cell and doesn’t affect the binding ability of the spike protein in the first place to a cellular receptor.
“Other cannabinoids like THC might work counter Antiviral Efficacy of CBD.”
How they did it — First, the researchers tested doses of between 0 and 10 micromolar CBD in human lung cells in a dish. The researchers dosed the cells with CBD for two hours and then exposed the cells to SARS-CoV-2. After two days, they went back to see how well the infection had taken root in the cells — CBD had “strongly inhibited viral replication,” according to the paper. They then tested CBD in monkey kidney cells and found the same result. They applied the same test to the original coronavirus strain, as well as the alpha, beta and gamma variants, and the results held up.
They then looked at other cannabinoids that are typically consumed alongside CBD, since many people in the real world consume cannabis whole, not just its components. But CBD alone stood out, the researchers write, and oddly enough, THC actually appeared to inhibit CBD’s beneficial effects.
“Notably, from this group, only CBD was an effective agent, while these structurally closely related congeners, which share common biosynthetic pathways and constitute the residual biogenetic complexity of CBD purified from C. sativa, exhibited no or only very limited antiviral activity,” the researchers to write.
When they turned to CBD’s two main metabolites — secondary compounds that the body produces after ingesting CBD — 7-OH-CBD stood out as being just as therapeutic as CBD itself. Interestingly, CBD and 7-OH-CBD together are used to treat seizures used.
“CBD treatment clearly inhibited Viral replication.”
By closely examining how CBD altered gene expression both in the virus and in cells after infection, the researchers found that the cannabinoid altered gene expression in the spike protein and also the body’s immune response to attack by the virus and the virus alters the stress it exerts on the cells. Encouragingly, CBD appears to help the body avoid the “cytokine storm,” a dangerous biological cascade linked to poorer health outcomes in people infected with Covid-19.
“CBD effectively reversed viral induction of cytokines, which can lead to a deadly cytokine storm in later stages of infection,” the researchers write.
They then tested the hypothesis on mice, which they injected with CBD twice a day for a week, and then exposed the mice to SARS-CoV-2 by letting them breathe the virus. After exposure, they injected the mice with CBD for four more days.
Medical marijuana has many uses, but smoking cannabis is unlikely to protect against Covid-19, this new study suggests. picture alliance/picture alliance/Getty Images
“CBD treatment significantly inhibited viral replication in the lungs and turbinates on day 5 post-infection, in a dose-dependent manner,” the researchers report. Dose dependent here means, importantly, that the more CBD the mice received, the better the results, so mice treated with a dose of 20 mg/kg CBD performed well, but mice treated with 80 mg/kg CBD performed well. kg of CBD treated performed even better.
If you think what we think – what all this has to do with humans – you know these researchers are wondering the same thing. So they went and looked at people getting CBD as a prescription drug for seizures.
Specifically, they examined the medical records of 1,212 people who were prescribed CBD 100mg/ml to treat seizures. The group had a significantly lower infection rate (6.2 percent) than a comparison group of people included in this study who did not receive such prescriptions (8.9 percent).
What comes next – This study is still preliminary, and the researchers are very careful to point out that people should not take CBD products and expect to be protected from Covid-19 based on these results alone. However, the results suggest that CBD has significant potential as a therapeutic for Covid-19 and may even help protect against infection.
“Our results suggest that CBD and its metabolite 7-OH-CBD can block SARS-CoV-2 infection in early and even later stages of infection,” the researchers conclude.
Taken together, the study results indicate that “further research on the potential of CBD to combat SARS-CoV-2 infection, such as Validation in other large multi-site electronic health datasets or prospective experimental designs,” the researchers say.
In other words, the researchers want to see larger analyzes that build on their own preliminary dive into analyzing people’s health records to see if there’s a link between CBD prescriptions and Covid-19 infection rates.
Additionally, the researchers warn that the CBD you can buy commercially is likely to be impure and of variable quality – so it’s hard to say what, if anything, they might be doing about Covid-19.
“Although many CBD and CBD-containing products are available on the market, they vary greatly in quality, CBD content, and their pharmacokinetic properties after oral administration, which are largely unknown,” the researchers note. “Other cannabinoids such as THC may counteract the antiviral efficacy of CBD.”
However, the ultimate test of CBD for treating Covid-19 will be large, randomized, controlled clinical trials. And researchers still can’t say what dose of CBD might have a therapeutic effect in humans.
“We encourage carefully designed, placebo-controlled clinical trials with known concentrations and highly characterized formulations to define the role of CBD in the prevention and treatment of early SARS-CoV-2 infection,” the researchers write.
“We strongly caution against the temptation to take CBD in currently available formulations, including edibles, inhalants, or topicals, as a preventive or treatment therapy at this time, particularly without knowledge of a rigorous randomized clinical trial of this natural product.”
Abstract: The spread of SARS-CoV-2 and the ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, effectively block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many of the effects of SARS-CoV-2 on host gene transcription. CBD partially inhibits SARS-CoV-2 replication by upregulating the stress response of the host IRE1α-RNase of the endoplasmic reticulum (ER) and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/mL oral solution according to medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative for early-stage SARS-CoV-2 infection and merits future clinical trials. We currently caution against the use of non-medicated formulations, including edibles, inhalants, or topical agents, as preventative or treatment therapy.
source https://www.bisayanews.com/2022/01/23/scientists-discover-cbd-and-not-thc-may-prevent-covid-19-infection-in-cells/
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