CBD and COVID-19

The most popular topic of research for 2020 is without a doubt the pandemic from COVID-19. During the last few months, there are more and more scientific articles and clinical studies about the coronavirus, but many of them create more questions than answers.

Some studies became quite popular even before they were peer-reviewed and officially published. Many of these publications were later retracted.

Nevertheless, there is an urgent need for new therapies and researchers from all over the world are investigating potential cures. One of the prevention strategies recently suggested by some researchers includes the well-known non-psychoactive compound of cannabis – Cannabidiol (CBD). In this article, we will take a deeper look at the evidence on CBD and its potential role as a preventive agent against COVID-19 and the various biologic systems it affects.

The Coronavirus Enters the Body via Specific Receptors

The coronavirus causing COVID-19 is named SARS-CoV-2. It uses two different receptors as entry points into human cells. The receptors are called angiotensin-converting enzyme II (ACE-2) and transmembrane protease serine 2 (TMPRSS-2). (1)

The ACE-2 are receptors are found in the lungs, heart, blood vessels, kidneys, intestines and other organs. (2, 3) This is why the infection affects mainly the lungs, but it is not limited there – there are atypical cases that present with diarrhea and severe cases with heart and kidney damage. ACE-2 receptors are also expressed in the mucosa of the oral cavity, especially the tongue, which is considered to be one of the main gateways for the entry of COVID-19. (4)

Inside the lungs, the coronavirus uses the ACE-2 receptor to enter a specific type of cells called “alveolar type II cells”. These are the most numerous cells in the alveoli. Alveoli are the tiny, balloon-shaped air sacs at the end of the respiratory tree where the gas exchange with the blood happens.

The alveolar type II cells produce a surfactant that prevents the collapse of the lungs by keeping the alveoli open, warding off fluid accumulation in the lungs and keeping the airways dry. (5) By attaching to the ACE-2 receptor, the virus enters and damages those cells. This can lead to a sudden drop in surfactant levels and a rapid respiratory collapse called ARDS (acute respiratory distress syndrome).

During this pandemic, it has been hypothesized by many authors that by modifying the expression of these receptors, it might reduce the risk and/or the severity of COVID-19.

CBD As a Possible Prevention Against COVID-19

In a recent study, Canadian scientists hypothesized that CBD might reduce the expression of ACE-2 receptors, which in return might inhibit the entry of the coronavirus inside the cells and reduce the risk of getting infected. (6) CBD is a phytocannabinoid naturally found in cannabis and this mechanism was proposed due to CBD’s anti-inflammatory and gene modulating properties. However, the article which makes these claims is still a preprint; it is not yet reviewed and approved by specialists in the field. Once it is peer-reviewed by experts and accepted it will be published in a scientific journal.

Furthermore, the study uses in vitro data only, the scientists used artificial human 3D models of oral, lung, and intestinal tissues. They also developed over 800 different extracts of Cannabis Sativa plant and identified 13 of them with high CBD levels which can modulate the ACE-2 expression in the 3D models, down-regulating the number of receptors expressed. According to the article, the other receptors used for entry by the coronavirus - TMPRSS2- were also down-regulated.

The researchers hypothesized that the extracts can be used as mouthwash products to reduce the expression of ACE-2 in the mouth and lower the risk of viral entry into the body. However, this is only a hypothesis that is yet unproven clinically. We need peer-reviewed trials in humans before we can make any claims that CBD can prevent COVID-19.

Another study has shown that various phytocompounds such as terpenes can have positive effects against the coronavirus which caused the SARS epidemic from 2002-2003. (7) Terpenes are the compounds that usually contribute to the odor of the plants. However, it is unclear if the specific terpenes from cannabis have similar anti-viral properties.

Besides, clinicians would strongly advise against smoking or vaping CBD-containing or any other products, due to the nature of COVID-19 and its pathology in the lungs. COVID-19 causes a respiratory condition that can seriously damage the lungs and one should avoid any potential risk of aggravating inflammation of the pulmonary endothelium.

How ACE-2 Regulation Affects COVID-19 Severity

Unfortunately, we have no information if CBD used by ingestion or inhalation, instead of locally as a mouthwash, is even safe for people with COVID-19.

Some medications have the opposite effect of CBD – they lead to the upregulation of ACE-2 receptors. These include some drugs classified as antihypertensive drugs such as ACE-inhibitors and Angiotensin Receptor Blockers (ARB) which are widely used by adults and the elderly. Due to the effects of these medications, there were concerns that these drugs might increase the severity and disease progression of COVID-19.

However, the role of ACE-2 in the body is to reduce the levels of the vasoconstrictor angiotensin-II (AT-II). Older studies have shown that AT-II might increase the risk of lung injury during infections and ACE-2 upregulation can have a protective role by lowering it. (8)

A systematic review and meta-analysis revealed a 34% reduction in the risk of pneumonia in patients when ACE inhibitors are used for the treatment of cardiovascular diseases. (9) This is why another study hypothesized the opposite – that maybe ACE-2 receptors are simply preoccupied with the virus during COVID-19 and they cannot lower the levels of angiotensin-II which could lead to lung damage. (10)

New studies reveal that, indeed, it might not be the upregulation of ACE-2, but their preoccupation with viral particles that increase the severity of COVID, and antihypertensive medication that upregulate ACE-2 have neutral or even favorable effects on COVID-19 patients.

The first study was published in JAMA and investigated 1178 patients with COVID-19. It concluded that ACEIs/ARBs are not associated with the severity or mortality of COVID-19. (11) Another study, published in Circulation Research which involved 188 COVID-9 patients taking ACEI/ARB and 940 without using ACEI/ARB reported lower mortality amongst the first group. (12)

These findings should be considered before using CBD systematically instead of locally in case of a present COVID-19 infection.

The Take-Home Message

Realistically, we have no evidence yet that CBD might prevent or reduce the risk of COVID-19 because the only scientific publication available is preliminary and still not peer-reviewed.

While the researchers' suggestions for CBD use is only as a mouthwash, we still lack any evidence on the effect and safety of CBD ingestion or inhalation during active COVID-19 infection.

Furthermore, people who smoke cannabis or tobacco might be at additional risk because COVID-19 is a respiratory infection that can result in permanent and severe lung damage. Smoking or vaping might increase pulmonary inflammation and the severity of the disease.

References:

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102627/
2. https://pubmed.ncbi.nlm.nih.gov/15141377/
3. https://pubmed.ncbi.nlm.nih.gov/10969042/
4. https://www.nature.com/articles/s41368-020-0074-x
5. https://www.sciencedirect.com/science/article/pii/S000527360000256X
6. https://www.preprints.org/manuscript/202004.0315/v1
7. https://pubmed.ncbi.nlm.nih.gov/17663539/
8. https://pubmed.ncbi.nlm.nih.gov/16001071/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394697/
10. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ddr.21656
11. https://jamanetwork.com/journals/jamacardiology/fullarticle/2765049
12. https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.317134