The cannabis plant is so much more than something humans ingest to feel some type of way. Rather, hemp contains myriad cannabinoids — some estimates peg the number at 100 different cannabinoid compounds — and many non-cannabinoid chemicals, too. 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 investigators at the University of Chicago reveal that CBD and one of its metabolites, 7-OH-CBD, prevents SARS-CoV-2, the virus that causes Covid-19, from infecting cells. Further, the researchers also tested CBD and 7-OH-CBD to see whether they could prevent Covid-19 infection in mice — and they do.
The metabolite 7-OH-CBD is particularly interesting, as this is a secondary chemical made when CBD is broken down by the body. Also of note is a finding that THC, taken with CBD, hampers the beneficial effects seen with CBD treatment alone.
“This essentially eliminates the feasibility 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 the hope of preventing or curing a Covid-19 infection.
“We caution against use of non-medical formulations including edibles, inhalants, or topicals as a preventative or treatment therapy at the present time,” the researchers write.
The study builds on the work of a cell study published earlier this month suggesting two other cannabinoids, CBDA and CBGA, prevent certain variants of the SARS-CoV-2 virus from infecting cells by interfering with a key step of infection: The virus spike protein’s ability to bind to the ACE2 receptor on the surface of cells.
Why it matters — This study is fresh 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 only in cells but in mice. Mice models are often used as a first step in testing out new medications for use in humans.
Further, the new study offers an explanation for why CBD may 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, thereby hampering an infection’s spread. It also appears to alter the immune system’s inflammatory response. This is a different treatment tactic than preventing infection from happening at all, as it is focused on what happens after exposure.
“To date, few therapies have been identified that 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 step,” they add.
Further, CBD offers great potential as a treatment against yet-to-emerge variants of the coronavirus, the researchers argue, 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 might act to counter CBD antiviral efficacy.”
How they did it — First, the researchers tested doses of between 0 and 10 micromolars of CBD in human lung cells in a dish. The researchers dosed the cells for two hours with CBD, and then they exposed the cells to SARS-CoV-2. After two days, they went back to see how well the infection had taken hold in the cells — CBD had “potently inhibited viral replication,” according to the paper. 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 held.
They then looked at other cannabinoids typically consumed along with CBD, because many people in the real world consume cannabis as a whole, not only its constituent parts. But CBD alone stood out, the researchers write, and curiously, THC appeared to actually inhibit CBD’s beneficial effects.
“Remarkably, of this group, only CBD was a potent agent, while no or very limited antiviral activity was exhibited by these structurally closely related congeners that share biosynthesis pathways and form the biogenetically determined residual complexity of CBD purified from C. sativa,” the researchers write.
When they turned to CBD’s two main metabolites — secondary compounds produced by the body after ingesting CBD — 7-OH-CBD stood out as being as therapeutic as CBD itself. Interestingly, CBD and 7-OH-CBD are used together to treat seizures.
“CBD treatment significantly inhibited viral replication.”
By looking closely at how CBD changed gene expression in both the virus and in cells post-infection, the researchers found the cannabinoid alters gene expression in the spike protein, as well as changing the body’s immune response to the attack mounted by the virus and the stress it puts on 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 viral induction of cytokines that can lead to the deadly cytokine storm at later stages of infection,” the researchers write.
They then tested the hypothesis in mice, which they injected twice a day with CBD for a week, and then they exposed the mice to SARS-CoV-2 by letting them breathe in the virus. After the exposure, they kept injecting the mice with CBD for four more days.
“CBD treatment significantly inhibited viral replication in 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 outcomes, so mice treated with a dose of 20 mg/kg of CBD fared well, but mice treated with 80 mg/kg of CBD fared even better.
If you’re thinking what we’re thinking — what has all this got to do with humans — then know that these researchers are wondering that, too. So they went and looked at people who receive CBD as a prescription medication for seizures.
Specifically, they looked at 1,212 people’s medical records who received prescriptions of CBD 100 mg/mL to treat seizures. The group had a significantly lower infection rate (6.2 percent) than a comparison group of people who do not receive such prescriptions (8.9 percent) included in this study.
What’s 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 indicate CBD may have significant potential as a therapeutic for Covid-19, and may even help to protect against infection happening 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’s findings show “further research into the potential of CBD to combat SARS-CoV-2 infection, such as validation in other large, multi-site electronic health record datasets or prospective experimental designs,” is needed the researchers say.
In other words, the researchers want to see bigger analyses building off their own tentative dive into analyzing people’s health records to see if there is an association between CBD prescriptions and Covid-19 infection rates.
Further, the researchers caution that the CBD you can buy commercially is likely not pure and of differing quality — so it is hard to say what they might do as far as Covid-19 goes, if anything.
“Although many CBD and CBD-containing products are available on the market, they vary vastly in quality, CBD content, and their pharmacokinetic properties after oral administration, which are mostly unknown,” the researchers state. “Other cannabinoids such as THC might act to counter CBD antiviral efficacy.”
The ultimate test of CBD for treating Covid-19 will be large, randomized, controlled clinical trials, however. And the researchers still can’t say what dose of CBD might have any therapeutic effect in humans.
“We advocate carefully designed placebo-controlled clinical trials with known concentrations and highly-characterized formulations in order to define CBD’s role in preventing and treating early SARS-CoV-2 infection,” the researchers write.
“We strongly caution against the temptation to take CBD in presently available formulations including edibles, inhalants or topicals as a preventative or treatment therapy at this time, especially without the knowledge of a rigorous randomized clinical trial with this natural product.”
Abstract: The spread of SARS-CoV-2 and 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, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.