Mind & Matter is a monthly column by Nick Jikomes, PhD, Leafly’s Director of Science and Innovation.
Cannabidiol (CBD) is a non-intoxicating cannabinoid famous for its ability to treat epilepsy. While that remains its only “official” (FDA-approved) use in humans, it has been associated with a wide variety of medical benefits ranging from anti-anxiety to anti-addiction effects. Most CBD studies have been preclinical experiments, which point to the possibility of therapeutic use for humans but don’t prove it.
The latest wave of CBD hype comes from studies suggesting it may act as an antiviral drug against SARS-CoV-2. This could be game-changing if true. CBD is widely available and safe for consumption even at high doses (assuming it’s lab-tested and high in purity).
But how compelling is the latest research?
Peer-reviewed doesn’t mean perfect
Multiple studies have been published in the past year suggesting that CBD or other cannabinoids have antiviral properties against SARS-CoV-2, the virus that causes COVID. But just because research is published in a peer-reviewed journal doesn’t mean its conclusions are rock solid. With a little prodding, any good scientist will tell you that a large percentage of papers are poor quality.
The most compelling recent study suggesting CBD could be an anti-COVID drug was conducted by a large team of scientists led by biochemist Dr. Marsha Rosner at the University of Chicago. To understand exactly what the study found, what it means, and what comes next, I spoke to Dr. Rosner and we broke the study down piece by piece.
Petri dish experiments: Is CBD antiviral?
Basic science often involves in vitro experiments, such as cells growing in a glass dish. These studies are simpler and cheaper to conduct compared to animal or human experiments. They also make it easier to understand the microscopic details of what’s going on. That’s where this study started: putting CBD onto human lung cells growing in a dish and measuring SARS-CoV-2 infection rates.
The basic result was that CBD inhibited SARS-CoV-2 replication–when cells were exposed to the virus in the presence of CBD, fewer of them tested positive for infection. This was true for CBD from four different sources—two commercial CBD makers and two chemical supply companies—all of which were confirmed to be high purity (~98%). This antiviral effect was observed against four different strains of SARS-CoV-2.
Do other cannabinoids have anti-Covid effects?
They tested several other cannabinoids, finding that only one of them, 7-OH-CBD (“seven hydroxy CBD”), had a clear antiviral effect. 7-OH-CBD is the metabolite of CBD, the product of your body breaking down CBD. Other cannabinoids, including THC, did not show a clear antiviral effect. In fact, they tested a 1:1 CBD/THC mixture that contained the same amount of CBD as in the CBD-only experiments, finding it had a weaker antiviral effect compared to CBD on its own. This suggests THC somehow interferes with CBD’s antiviral effect. This implies that products containing more than trace THC levels are unlikely to deter SARS-CoV-2, even if the antiviral CBD effect is seen in future clinical trials.
Understanding the mechanism at work
Using human cells growing in a dish, scientists can figure out the specific details of how a drug achieves its effects—in other words, they can uncover the mechanism. In this case, they determined that CBD was not preventing SARS-CoV-2 from entering a cell. Instead, CBD interfered with what the virus did once inside the cell.
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Under normal conditions, the virus gets into a cell and hijacks its replication machinery. The virus does this, in part, by altering gene expression. It causes some genes to turn “on” and some to turn “off” to trick the cell into making virus particles. CBD was itself capable of changing gene expression, in ways that interfered with the virus’s ability to do so. This rendered the virus less capable of making copies of itself.
One significant observation researchers made was that CBD exerted an antiviral effect even when introduced to cells several hours after SARS-CoV-2 exposure. If CBD is proven effective in clinical trials, this hints at the possibility it might be useful even when ingested after exposure to the virus.
Next step: Trying it on mice
Experiments that look promising in a dish often don’t pan out in animals. The next step was to test CBD in rodents.
Scientists took special mice engineered to have lung cells capable of being infected by SARS-CoV-2, similar to the way the virus infects human lung tissue. They exposed these mice to SARS-CoV-2 with and without several days of CBD treatment leading up to the exposure. CBD significantly reduced the amount of viral particles detected in lung tissue.
The effect was dose-dependent: The higher the CBD dose, the fewer the viral particles detected.
Then looking at human medical records
Human clinical trials are used to prove cause-and-effect, but they require lots of time and money to execute. To get a sense of whether CBD use is at least correlated with lower rates of COVID in humans, the team analyzed a large database of medical records. They looked for patients who had been taking prescription CBD (the FDA-approved medicine Epidiolex), which is used to treat seizures. Such patients take large daily doses of CBD. Would they have lower rates of COVID?
To be as rigorous as possible, they took the records of Epidiolex patients (531 in total) and compared them to a matched cohort of patients who were chosen to be as similar as possible to the Epidiolex group across a number of factors (i.e. similar age, sex, etc.) but who were not taking Epidiolex. The result: Patients who had been taking Epidiolex were half as likely to have tested positive for COVID.
Again, this is just a correlation, and could be explained by unknown variables that couldn’t be controlled for. But together with the previous results, it tells us that clinical trials are worth a shot.
Dosage remains an important question
An important question to ask is how much CBD is being used in these experiments. For humans taking prescription CBD (Epidiolex), the dose is typically hundredsof milligrams per day, well above what you will get from most store-bought CBD products. In the rodent experiments, researchers gave mice either 20 or 80 milligrams per kilogram of their weight, injecting them with lab-grade CBD twice daily. Roughly speaking, that would be like a 150-pound person taking either ~200 or ~1300 mg CBD doses twice per day.
Mega doses of store-bought CBD like that are not practical, or affordable, for most people. When you buy store-bought CBD products, such as gummies, they are often 5-10 mg each. And due to CBD’s low oral bioavailability—your body only uses a fraction of any CBD you swallow—we might even be talking about larger doses still. CBD tinctures often contain hundreds or thousands of milligrams of CBD per bottle. However, these products are more costly and no one buys them expecting to down one or two whole bottles per day.
Even so, we know that CBD is widely available and safe to consume even at very large doses. So although we don’t yet have the clinical data proving high-dose CBD has anti-COVID effects in humans, is there any harm in boosting your daily dose of store-bought CBD to help prevent an infection?
Maybe so, maybe not. There are a number of factors to consider.
So does the purity of the CBD
A major problem in the CBD and cannabis industries is the purity and reliability of consumer products.
Even though products in most state-licensed cannabis stores must be lab tested, we know there are ways for companies to game those requirements. And most CBD products are sold outside the state-licensed cannabis system, which means they’re not required to conduct any testing at all.
There are plenty of examples of branded CBD and cannabis products that are either far less potent than advertised, or even contain harmful contaminants even though they “passed” testing requirements.
So: Will this work in humans?
While these results are intriguing, we know that experiments that look promising in preclinical work often fail in human trials. There are many reasons for this, but a lot of it simply boils down to the fact that rodents and humans are just not the same.
Rosner’s team is in the process of launching a small pilot study in humans to get some preliminary clinical data. The results should arrive later in 2022, and could determine whether larger, more expensive clinical trials get funded.
Given that CBD is already widely available and is not owned by a single drug company, where is the funding for this clinical research coming from?
Seeking support for further research
The National Institutes of Health (NIH) is the largest source of research funding in the US. Given the public health crisis we have all been immersed in for the past two years, I was surprised to learn that NIH has not provided any support for Rosner’s CBD work so far. As she told me, they want to see positive results from smaller human pilot studies before funding larger trials.
Given that prescription CBD in the form of Epidiolex is already a commercial success, Rosner approached the maker of Epidiolex (GW Pharma, recently acquired by Jazz Pharmaceuticals for $7.2 billion) about collaborating on CBD clinical trials.
“We have tried to approach the company that makes Epidiolex,” she said. “We’ve actually had a lot of conversations with GW Pharmaceuticals. But somewhere in the middle of our study they got taken over by Jazz Pharmaceuticals, and [since then] they have not seemed to have any interest in pursuing this.”
When I asked why there was no interest in pursuing this research, Rosner simply told me, “We can all speculate.”
Very promising, but not a vaccine replacement
It will be interesting to see what comes of this pilot study testing CBD in human patients infected with SARS-CoV-2.
If the trials show positive results, CBD will become one of several drugs already shown or purported to have anti-COVID properties. Some of these drugs are on patent, and others are generic. There has been significant controversy about how different potential antivirals have been studied or promoted based on their profit-generating potential.
In the end, Rosner cautions against making too big a leap too early. “We are not suggesting that CBD should replace vaccines,” she said. “Vaccines are not perfect, we all know this. We get breakthrough infections. But at the moment vaccines are the best way we have of protecting ourselves. I would think of CBD as a tool in the toolbox—another tool that we have—but not a replacement for what exists.”