In this article, we will take a look at the antiviral effects of CBD in relation to the COVID-19 virus.
First things first:
While CBD has anti-viral properties and several studies show that CBD could inhibit Covid-19 infection, there’s no clinical evidence showing that CBD can treat, cure, or prevent COVID-19.
Clinical trials are needed to truly determine the effects of CBD on Covid-19 infection in humans.
The researchers in all CBD and COVID-19-related studies caution against proposing any type of cannabis extract as a potential treatment for COVID-19.
That being said, the focus of this article is several studies recently published in various scientific journals that looked at the effects of CBD on COVID-19 infection.
Table of contents:
CBD Inhibits Covid-19 Replication and Promotes the Host Innate Immune Response
Has Anti-Inflammatory Effects in COVID-19-Related Inflammation in Lung Epithelial Cells
Assessment of Antiviral Potencies of Cannabinoids Against SARS-CoV-2
Before we take a deeper dive into these studies, let’s examine CBD’s antiviral and anti-inflammatory properties.
CBD’s Antiviral Effects
Although there’s some scientific evidence that CBD has anti-viral effects, this evidence is limited and highly circumstantial.
What does antiviral mean?
Antiviral effects can be direct or indirect.
The direct part of antiviral effects is related to a compound’s ability to stop the virus from replicating in cells.
The indirect part of antiviral effects is related to the consequences of the actual infection. A viral infection can lead to a strong inflammatory response by the human immune system. This inflammatory response can be so strong that it causes organ failure or even death.
In the case of such a strong inflammatory response within the context of a virus infection, any compound that reduces this inflammatory response has indirect antiviral effects.
Interestingly, at least three studies found that CBD may have both direct and indirect antiviral effects when it comes to COVID-19 infection.
Study 1: CBD Inhibits Covid-19 Replication and Promotes the Host Innate Immune Response
This study looked at the effects of CBD on COVID-19 replication and the immune system’s inflammatory response (1).
Interestingly, the study found that CBD and its active metabolite, 7-OH-CBD:
- Can block COVID-19 infection at early stages of infection, and;
- CBD administration is associated with a lower risk of Covid-19 infection in humans.
Several mechanisms of action are thought to be responsible for CBD’s anti-viral effects within the context of Covid-19.
Interferons
The first one is related to CBD’s stimulation of the interferon pathway.
Interferons are a group of proteins that can battle viruses. They interfere with the viral replication process by stopping the release of viruses from infected cells.
Covid-19 infection suppresses the release and signaling of interferons.
Without going into the biomolecular specifics, CBD stimulates and normalizes interferon signaling in various ways.
Interesting note: interferons have been clinically tested as potential treatments for COVID-19.
Cytokines
Another way CBD may reduce severe symptoms caused by COVID-19 is by reversing the release of pro-inflammatory cytokines.
Cytokines are a class of pro- or anti-inflammatory proteins released by cells that serve a variety of functions. They are vital in the body’s immune response. Cytokine signaling can be triggered and increased with infections that are created by viruses, bacteria, and parasites.
An inflammatory response by the immune system is a perfectly normal response to infections. In the case of an infection, the body then releases pro-inflammatory cytokines and helps the body’s recovery process.
However:
When the immune system overacts to the infection with cytokine signaling and releases significantly more pro-inflammatory cytokines than it should, a ‘cytokine storm’ can occur.
In the case of cytokine storms, the immune system produces a much too strong inflammatory response to the infection. A cytokine storm can in the worst cases lead to death.
It’s thought that COVID-19, in the later stages of infection, can induce such a cytokine storm.
This study showed that CBD can reverse COVID-19-induced cytokine release that in turn is caused by changes in host gene expression.
While the exact mechanism of action responsible for this effect needs further research, in a different study (2), it’s hypothesized that CBD acts as an ‘inverse agonist’ of the Cannabinoid 2 receptor (CB2).
This means CBD can block the activation of the CB2 receptor. Preventing the activation of the CB2 receptor, in turn, has been shown to inhibit immune cell migration. The inhibition of immune cell migration, in turn, is associated with anti-inflammatory effects.
CBD Users Have a Statistically Lower Chance to Contract COVID-19
This study also analyzed 93000 patients tested for COVID-19 at the University of Chicago Medical Center and whether they had any cannabinoids in their medical records. 400 Patients had one or more cannabinoids in their medical records.
Out of all patients, 10% tested positive for COVID-19.
Out of these 400 patients with a history of using cannabinoids, only 5.7% tested positive for COVID-19.
Out of these 400 patients, there were 85 CBD users. Out of these 85 CBD users, only 1.2% tested positive for COVID-19.
But correlation does not mean causation, and the researchers rightfully note that other factors like age, race, or pre-existing conditions could explain this variance.
To do a more objective test, before any COVID-19 testing, the researchers matched 82 patients who were prescribed Epidiolex (an FDA-approved CBD solution) to patients with no cannabinoid use but had similar other characteristics like:
- Demographics;
- Pre-existing conditions, and;
- Medication records in the past two years.
In the follow-up period, out of the patients that weren’t prescribed any cannabinoids 12.2% tested positive for COVID-19.
Out of the patients that were prescribed the FDA-approved CBD solution, only 1.2% of the patients tested positive for COVID-19.
Again, correlation doesn’t mean causation, but these findings are interesting nonetheless.
Study 2: CBD Has Anti-Inflammatory Effects in COVID-19-Related Inflammation in Lung Epithelial Cells
This study looked at the effects of CBD on lung epithelial cells in the context of COVID-19 related lung inflammation (3).
By now, you know that COVID-19 can induce a strong inflammatory response by the host’s immune system. As a reaction to the COVID-19 infection, the host’s immune system releases pro-inflammatory cytokines.
This study tested three different CBD-containing extracts and a pharmaceutical drug:
- One extract containing CBD, CBG, THCV, and multiple terpenes (CBD-extract 1);
- One extract containing only cannabinoids CBD, CBG, and THCV (CBD-extract 2), and;
- One extract containing only CBD;
- Dexamethasone (a drug that decreases your immune system’s response to various diseases).
The researchers looked at what effects these ‘medicines’ had on various inflammatory markers.
They found that all CBD extracts reduced the following pro-inflammatory cytokine levels in a lung epithelial (A549) cell line:
- IL-8;
- IL-6;
- CCL2, and;
- CCL7.
In the case of CCl2 and CCl7 cytokines, dexamethasone was more effective in reducing their expression than the CBD extracts.
The Renin-Angiotensin System and ACE2 Receptors
The renin-angiotensin system (RAS) is a hormonal system involved in various cardiovascular functions.
Patients with severe symptoms of COVID-19 are shown to have a disrupted renin-angiotensin system.
The ACE2 receptor is part of the renin-angiotensin system. Patients with severe symptoms of COVID-19 show that their ACE2 receptor can be upregulated 199-fold. It’s hypothesized that this ACE2 upregulation is one of the leading factors leading to a disrupted renin-angiotensin system in COVID-19 patients.
The terpene-rich CBD extract, and to a lesser extent the terpene-free CBD extract and dexamethasone significantly reduced ACE2 expression in cells.
The researchers caution that the advantages and disadvantages of this reduction in ACE2 expression are currently disputed and caution against using CBD extracts for these purposes until further research shows the exact effects.
Macrophages
The researchers also looked at what effects both CBD extracts had on cytokine expression in macrophages.
Macrophages are a type of white blood cell that has an important role in your body’s immune system. They fight microorganisms and clean dead cells for example.
The dysfunction of these macrophages is one of the abnormal characteristics in some severe COVID-19 patients.
The study found that both CBD-extract 1 and CBD-extract 2, and to a lesser extent the CBD-only extract as well, increased the effectiveness of macrophages (white blood cells).
The researchers hypothesize that this increased effectiveness of macrophages caused by the CBD-extracts may lead to an improved clearance of respiratory viruses, which could be especially effective in the first phase of the immune response to COVID-19.
Although they caution that macrophages themselves can be infected by the virus and the advantages and disadvantages of increasing macrophage activity should be considered carefully.
One interesting note is that although the terpene-free CBD extract influenced the functional programming of macrophages improving how they get activated (macrophage polarization), it didn’t stimulate the actual killing and removal of invading pathogens like viruses by the macrophages (phagocytosis activity).
The terpene-rich CBD extract did improve the actual killing and removal of invading pathogens like viruses by the macrophages.
In the second phase of the immune response to COVID-19 (the immune system failed to eliminate the virus), macrophages have a major pro-inflammatory role by releasing pro-inflammatory cytokines.
Interestingly, the CBD extract containing terpenes (CBD-extract 1), substantially increased pro-inflammatory cytokine expression in macrophages. The terpene-free CBD extract (CBD-extract 2) had a much less significant pro-inflammatory effect in macrophages.
It seems that either the terpenes or the interaction between cannabinoids and terpenes produce a pro-inflammatory effect in macrophages in the second phase of COVID-19 infection.
The researchers again caution that based on their study results a cannabis-based treatment of COVID-19 in the second phase of the infection may lead to a worsening of the ‘cytokine storm’. Therefore, no such treatment should be given before it’s exactly clear what combination of cannabinoids and/or terpenes prevents such a worsening.
Study 3: Assessment of Antiviral Potencies of Cannabinoids Against SARS-CoV-2
This study looked at antiviral effects of various cannabinoids against COVID-19 (4), including:
- CBD;
- CBDA;
- THC;
- THCA, and;
- CBN.
The researchers found that especially CBD and THC bind to and inhibit the SARS-CoV-2 Mpro enzyme. SARS-CoV-2 Mpro is a protease enzyme and plays a critical role in the replication process of the COVID-19 virus.
They also found that both CBD and THC increase anti-inflammatory cytokines and reduce pro-inflammatory cytokines levels in lung cells.
When compared to the reference drugs:
- Lopinavir,
- Chloroquine, and,
- Remdesivir,
They observed that both CBD and THC had more potent antiviral effects against COVID-19.
The researchers hypothesize that both CBD and THC’s anti-inflammatory effects within the context of COVID-19 are related to their activation of the CB2 receptor.
Conclusion
Currently, there’s no scientific evidence suggesting that CBD can treat, cure or prevent COVID-19.
However, some evidence is suggesting that CBD may:
- Reduce pro-inflammatory cytokine levels and thus reduce the immune system’s inflammatory response to the infection;
- Increase anti-inflammatory cytokine levels and thus reduce the immune system’s inflammatory response to the infection;
- Block the SARS-CoV-2 Mpro protease enzyme that plays an important role in the virus replication process;
- Increase the effectiveness of macrophages (a type of white blood cells) in fighting off the virus;
- Decrease ACE2 expression in cells. Upregulated ACE2 expression has a key role in the disruption of the renin-angiotensin system (involved in various cardiovascular functions);
- Increase interferon signaling. Interferons are proteins that block the replication process of a virus.
Further research should point out whether CBD has any potential role in the treatment or prevention of COVID-19, whether that’s alone or combined with other drugs and/or compounds.
What’s Next…
Go to our CBD Hub to learn more about CBD-related topics.
Scientific References:
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Nguyen, L. C., Yang, D., Nicolaescu, V., Best, T. J., Ohtsuki, T., Chen, S. N., . . . Rosner, M. R. (2021). Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response. COVID-19 SARS-CoV-2 Preprints from MedRxiv and BioRxiv. Published. https://doi.org/10.1101/2021.03.10.432967
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Raj, V., Park, J. G., Cho, K. H., Choi, P., Kim, T., Ham, J., & Lee, J. (2021). Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches. International Journal of Biological Macromolecules, 168, 474–485. https://doi.org/10.1016/j.ijbiomac.2020.12.020
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Anil, S. M., Shalev, N., Vinayaka, A. C., Nadarajan, S., Namdar, D., Belausov, E., . . . Koltai, H. (2021). Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-81049-2
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Raj, V., Park, J. G., Cho, K. H., Choi, P., Kim, T., Ham, J., & Lee, J. (2021b). Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches. International Journal of Biological Macromolecules, 168, 474–485. https://doi.org/10.1016/j.ijbiomac.2020.12.020
