The cannabis plant is so much more than something humans ingest to feel one way or another. On the contrary, hemp contains a myriad of cannabinoids – some estimates put the number at 100 different cannabinoid compounds – and many non-cannabinoid chemicals as well. Today, scientists are testing two of the best-known cannabinoids, THC (tetrahydrocannabinol) and CBD (cannabidiol): Could either of these compounds offer a potential treatment for Covid? -19?
What’s up – In an article published this week in the journal Scientists progress, researchers led by investigators from the University of Chicago reveal that CBD and one of its metabolites, 7-OH-CBD, prevent SARS-CoV-2, the virus that causes Covid-19, from infect cells. Additionally, the researchers also tested CBD and 7-OH-CBD to see if they could prevent Covid-19 infection in mice – and they do.
Of particular interest is the 7-OH-CBD metabolite, as it is a secondary chemical made when CBD is broken down by the body. Also of note is a 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 equally important, 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 caution against the use of non-medical formulations, including edibles, inhalants, or topicals as preventative or therapeutic therapy at this time,” the researchers write.
The study builds on the work of a cell study published earlier this month suggesting that two other cannabinoids, CBDA and CBGA, prevent certain variants of the SARS-CoV-2 virus from infecting cells by interfering with a key step in infection: the virus’s spike protein ability to bind to the ACE2 receptor on the cell surface.
Why is it important – This study is new evidence that cannabinoids may be an untapped source of treatments for Covid-19, but it also takes the research, which is still preliminary, further by testing the hypothesis not just in cells but in mice. Mouse models are often used as the first step in testing new drugs for use in humans.
Additionally, the new study offers an explanation of why CBD can prevent an infection from taking hold – it appears that after SARS-CoV-2 enters a cell, CBD interferes with the virus’s ability to replicate, thus hindering the spread of an infection. It also appears to modify the inflammatory response of the immune system. This is a different treatment tactic than infection prevention because it focuses on what happens after exposure.
“To date, few therapies have been identified to block SARS-CoV-2 replication and viral production,” the researchers write in the study.
“CBD acts early in the infection cycle, in a post-entry stage,” they add.
Additionally, CBD offers great potential as a treatment for yet-to-emerge variants of the coronavirus, researchers say, because it works to prevent replication after SARS-CoV-2 enters a cell, not to interfere with the spike protein’s ability to bind. to a cellular receptor in the first place.
“Other cannabinoids such as THC may act to counter Antiviral efficacy of CBD.
How they did — First, the researchers tested doses between 0 and 10 micromolar of CBD in human lung cells in a dish. The researchers dosed the cells for two hours with CBD, then they exposed the cells to SARS-CoV-2. After two days, they returned to see how well the infection had taken hold in the cells – the CBD had “potently inhibited viral replication”, according to the article. They then tested CBD in monkey kidney cells, finding 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 still hold.
They then looked at other cannabinoids commonly consumed with CBD, as many people in the real world consume cannabis as a whole, not just its components. But only CBD stood out, the researchers write, and curiously, THC actually seems to inhibit the beneficial effects of CBD.
“Remarkably, of this group, only CBD was a potent agent, whereas no antiviral or very limited activity was exhibited by these structurally closely related congeners that share biosynthetic pathways and form the biogenetically determined residual complexity of CBD. purified from C. sativa”, write the researchers.
When they looked at the two main metabolites of CBD – secondary compounds produced by the body after ingesting CBD – 7-OH-CBD was found to be as therapeutic as CBD itself. Interestingly, CBD and 7-OH-CBD are used together to treat seizures.
“CBD treatment significantly inhibited viral replication.
Looking closely at how CBD altered gene expression both in the virus and in cells after infection, the researchers found that the cannabinoid alters gene expression in the spike protein, as well as the body’s immune response to the mounting attack by the virus and the stress it places on the cells. Encouragingly, CBD appears to help the body avoid the “cytokine storm,” a dangerous biological cascade associated with poorer health outcomes in people infected with Covid-19.
“CBD effectively reversed the viral induction of cytokines that can lead to the lethal cytokine storm at later stages of infection,” the researchers write.
They then tested the hypothesis in mice, injecting them with CBD twice daily for a week, then exposing the mice to SARS-CoV-2 by letting them breathe in the virus. After the exposure, they continued to inject the mice with CBD for another four days.
“CBD treatment significantly inhibited viral replication in the lungs and nasal turbinates at day 5 post-infection in a dose-dependent manner,” the researchers report. Dose dependent, importantly, here means that the more CBD the mice received, the better their results were, so mice treated with a dose of 20 mg/kg CBD did well, but mice treated with 80 mg/kg of CBD performed even better. .
If you think about what we think – what does all this have to do with humans – then know that these researchers are wondering that too. So they went to people who were receiving CBD as a prescription medication for seizures.
Specifically, they reviewed the medical records of 1,212 people who received prescriptions for CBD 100 mg/mL to treat seizures. The group had a significantly lower infection rate (6.2%) than a comparison group of people who do not receive such prescriptions (8.9%) included in this study.
And after – This study is still preliminary, and the researchers are 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 indicate that CBD may have significant potential as a therapeutic for Covid-19, and may even help protect against the infection that occurs in the first place.
“Our results suggest that CBD and its metabolite 7-OH-CBD can block SARS-CoV-2 infection at early and even later stages of infection,” the researchers conclude.
Taken together, the study results show that “further research into the potential of CBD to fight SARS-CoV-2 infection, such as validation in other large health record datasets multi-site electronics or forward-looking experimental designs,” are needed, according to the researchers.
In other words, the researchers want to see larger analyzes build on their own tentative dive into analyzing people’s health records to see if there’s an association between CBD prescriptions and levels of Covid-19 infection.
Additionally, the researchers warn that the CBD you can buy commercially is likely not pure and of different quality – so it’s hard to say what they might do in regards to Covid-19, if any. .
“Although many CBD and CBD-containing products are available on the market, their quality, CBD content and pharmacokinetic properties after oral administration, which are mostly unknown, vary considerably,” the researchers state. “Other cannabinoids such as THC may act to counter the antiviral efficacy of CBD.”
The ultimate test of CBD for the treatment of Covid-19, however, 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 advocate 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 preventative or therapeutic therapy at this time, especially without the knowledge of a rigorous randomized clinical trial with this natural product.”
Summary: The spread of SARS-CoV-2 and the ongoing COVID-19 pandemic highlight the need for new treatments. Here we report that cannabidiol (CBD) inhibits SARS-CoV-2 infection in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently 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 host’s endoplasmic reticulum (ER) IRE1α RNase stress response 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 tests for SARS-CoV-2. This study highlights CBD as a potential preventive agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against the use of non-medical formulations, including edible, inhaled, or topical products, as a preventative treatment or treatment at this time.