A groundbreaking new study out of two Oregon universities has identified an unusual naturally-occuring substance as a promising tool to prevent COVID-19 infections: cannabis.
Published in the peer-reviewed Journal of Natural Products, the study identified three cannabis compounds—non-psychoactive precursors found in the plant before it’s converted into the stuff that gets you high—as being notably effective at blocking the entry of SARS-COV-2 into human cells by glomming onto the virus’s spike protein. The study is an early sign that cannabis could be an effective tool in the arsenal of global coronavirus responses; but with piecemeal laws and pushback from federal agencies, the future of cannabis in COVID-19 treatment remains unknown.
Here, Dr. Richard van Breemen, first author on the study and professor of medicinal chemistry at the Linus Pauling Institute at Oregon State University, tells Motherboard about his findings, the public response to the study, the legal challenges he encountered in this research, and why cannabis-derived gummies might just be an important public health intervention.
Motherboard: Your paper is really making the rounds—congratulations! Can you walk me through your key findings?
Dr. Richard van Breemen: Our interest has always been in discovering natural products that have medicinal value. With COVID, we thought we'd go about trying to find natural products that can stop the virus from infecting cells or inhibit their ability to replicate and go on to infect other individuals. We decided to attack the virus at the starting point, where it enters the cell. That's the exact same point at which antibodies attack the virus.
We asked the question: “Could small molecules from nature, like from plants, have the same ability to stop the virus from infecting a cell if they had an ability to bind to the surface of the virus and specifically to the spike protein of the virus, which is what's making contact with the human cell and enabling it to infect the cell?”
Initially, when we proposed this to the National Institutes of Health (NIH) back in 2020, one of the reviewers said, no one’s made the proof of principle that this can work. So they didn't give me the money. We did it anyway, and we've established this principle that small molecules including natural products, in this case from hemp, have the ability to stop the virus from infecting human cells.
We were looking at black cohosh, and red clover and licorice, and we added hemp, and we discovered three compounds in hemp that had this high ability to bind to the spike protein. And we even determined that some of them bind to sites on that spike protein and synergistically they can have a bigger effect than if one is using one compound at a time instead of the mixture. So we think the mixture of cannabidiolic acid (CBD-A), cannabigerolic acid (CBG-A), and tetrahydrocannabinolic acid (THC-A) would be more effective than any one of them alone. So this speaks to the idea that the supplement, containing a complex extract of a plant, sometimes is better than monotherapy in the traditional drug approach, where you purify it and use only one compound at a time.
I did see in the study that, crucially, you couldn't really test THC-A in the ways that you wanted to, because it's a controlled substance, and you just weren't able to get your hands on enough of it to test it. Is that right?
That is correct. We screened extracts of hemp, and there are traces of THC-A in these extracts. And so we identified it, but we weren't allowed, actually due to campus rules. We weren't allowed to purify it and even test it alone, because it can be converted to THC. If one heats it, the acid group can be removed and chemically it transforms into a psychoactive substance, but THC-A alone is not psychoactive.
Neither CBD-A nor CBG-A are psychoactive, right? So what we're looking at is a little more complicated than smoking weed to prevent COVID-19 infection. What we're talking about is something that would be orally ingested. What do you envision for that?
I envision oral administration in the form of a dietary supplement like a pill or an oil or a gummy, something like that. We all know that if we get exposed, we go to meet a friend and the friend tells us later they've tested positive for COVID. Then, we're all worried about getting sick. That's the time I would recommend taking a supplement that has the capability of preventing infection. But I don't advocate these particular compounds as a treatment or cure for someone who's hospitalized and severely ill. I think we need combinations of therapies that might include drugs that stop the virus at other points in its lifecycle for that, but as a weakly active, but nevertheless, I think effective prevention measure. I think this is a good place to use this dietary supplement. I think it can help keep people healthy.
This study has made waves on the internet, and it could contribute to public perception that recreationally smoking marijuana would have the same effect on COVID-19 prevention as ingesting an oral supplement, like you describe.
The active compounds we've discovered in hemp are cannabidiolic acid, CBD-A, CBG-A, and THC-A. ‘A’ stands for an acid group, a carboxylic acid — this group can be removed upon treatment. So if these hemp products containing these compounds are smoked or vaped, the heat exposure could cause the chemical decomposition or conversion of CBD-A to CBD, CBG-A to CBG, and THC-A to THC. So, we know that CBD, CBG and THC are not active against the virus. So, we would recommend in favor of an oral administration of these compounds instead of smoking them, inhaling them from vaping.
So, just to be clear: Smoking these compounds would not have the same effect on COVID-19 infection risk as ingesting them orally?
We certainly expect it would have a reduced effect. I haven't done the experiments to see how rapidly this conversion takes place and what the temperature limits are. But we do know that the cannabidiolic acid is unstable in heat.
Another study out of the University of Waterloo, in Ontario, Canada, offered evidence that ingesting CBD, as opposed to CBD-A, could “prime” the immune system for COVID-19 protection. Do you have any thoughts on this finding?
I've not had a chance to read that one yet. But there have been reports that some of the other connected cannabinoids like CBD certainly have anti-inflammatory activity. And of course, for COVID patients who are suffering what they call a “cytokine storm,” which is an immune response that causes a lot of inflammation, any therapeutic treatment that reduces that inflammation is a good thing. So, I'm sure the CBD would be beneficial in that respect.
You mentioned some pushback from the NIH in terms of funding. Can you talk to me a little bit more about the legal framework for cannabis-based medicine or research around cannabis. Have you come up against any other roadblocks like that, in your work broadly and with this study in particular?
There's always legal issues when the federal government makes one rule and the states make another rule. We are seeing that every year the rules are changing governing how one can use hemp and have constituents for research or even personal use. At the moment, the Department of Agriculture is allowing hemp cultivation. We have a research center at the Oregon State University that's focused on helping develop products of all kinds, whether for building purposes for fiber for agricultural use to feed livestock, or for medicinal value and so forth. My group is interested in the medicinal aspects of hemp. There is one drug, cannabidiol, CBD product approved for the treatment of juvenile epilepsy. It's a complex plant. I think there will be other drugs that will eventually be discovered and developed from hemp. And perhaps we've just found some.
Do you think that federal legalization could be sort of a new frontier and research in this realm?
Absolutely, yes. Hemp is an unusual plant in the sense that it has several unique classes of compounds not found elsewhere in nature. It's rich in compounds that have bioavailability. Often, we’ll do research on a plant and find compounds that, in a lab setting, seem to be effective and a mechanism that could be beneficial for health. But then when doing a human study, we find maybe they're not as active because they don't reach the bloodstream if given in pill form. Hemp is different. We know that many constituents of hemp are active. We know that they’re active when given in oral, when given by inhalation, and given by transdermal patches and so forth. So, hemp is unusually rich in compounds with known biological activity, and they're able to reach the human bloodstream and have effects. And they have a high degree of safety!
Looking forward, do you have any thoughts on how you hope to see your findings contribute to scientific understanding of cannabis and COVID? And federal response to the pandemic and emerging variants?
In answer to one of my grant reviews, we have established the principle that small molecules can prevent viral infection. So that, I believe, is an important sort of basic science discovery. Secondly, we found compounds in hemp that have, at least in cell culture with live virus, the ability to stop cells from being infected. I would love to see a follow up study where we start developing what the oral dose ought to be. How can we maintain how many doses per day and what level do we need to help prevent viral infection or transmission? And I think we have a product that should be safe to use eventually. I can envision hemp extracts being used to help people stay healthy and help stop them getting sick from COVID.
Have you had the chance to check out any of the responses to your research on the internet, or, crucially, the memes that have been circulating about it?
I'm doing my best to keep up with messages as they come in. I've really not had a chance to check the response on the internet yet. So, I'm really delighted that our work is getting attention. I'm glad people are viewing it as important. We, of course, hoped it would be viewed that way. We're very thankful everybody likes it.
Thank you so much for your time. Is there anything else you’d like to add?
I'm just going to keep my fingers crossed that my next NIH grant proposal gets funded.