New Cannabis Plant Extracts Could Protect Against COVID-19

Canadian researchers conducted a study suggesting that the novel Cannabis sativa the extracts may decrease the levels of the host cell receptor that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) uses to gain viral entry into target tissues.

SARS-CoV-2 is the causative agent of the current 2019 coronavirus disease pandemic (COVID-19) which continues to sweep the world, threatening public health and the global economy.

The team – from the University of Lethbridge and Pathway Rx Inc., Lethbridge – has developed hundreds of C. sativa cultivars and tested 23 extracts in artificial 3D human models of oral, respiratory and intestinal tissue.

As recently reported in the newspaper Aging, 13 of the extracts down-regulated the expression of angiotensin converting enzyme 2 (ACE2) of the host cell receptor SARS-CoV-2.

“The downregulation observed in the expression of the ACE2 gene by several tested extracts of C. sativa cultivars is a new and crucial discovery, ”say the researchers.

“Although our most effective extracts require large-scale validation, our study is important for future analyzes of the effects of medical cannabis on COVID-19,” write Olga Kovalchuk and colleagues.

“Downregulation of ACE2 levels in gateway tissues may be a plausible strategy”

The ACE2 receptor that SARS-CoV-2 and other coronaviruses use to access host cells is expressed in a range of tissues, including the lungs, nasal mucosa, kidneys, and the gastrointestinal tract.

A recent study reported high levels of ACE2 expression in oral epithelial tissues and suggested that the oral cavity could be an important target for prevention strategies.

Numerous studies have also reported elevated levels of ACE2 expression in the lower respiratory tract of patients with chronic obstructive pulmonary disease (COPD). This group of patients is associated with increased susceptibility to COVID-19 and more serious illness.

“Downregulation of ACE2 levels in gateway tissues may therefore be a plausible strategy to decrease susceptibility to disease,” said Kovalchuk and colleagues.

Where is Cannabis sativa Come in?

C. sativa, especially cultivars rich in cannabidiol (CBD), have already been shown to alter gene expression and have anti-inflammatory and anti-cancer properties.

However, the effects of C. sativa on ACE2 expression is not known, the team says.

Working under a research license from Health Canada, the researchers developed more than 800 new C. sativa cultivars and extracts. They then used artificial 3D human models to test whether 23 of the CBD-rich extracts would alter the expression of ACE2 in the target tissues of COVID-19.

Since inflammation is an important component of viral disease, the researchers also looked at the effect of the extracts on ACE2 expression in 3D tissue models stimulated by inflammation.

Using 3D artificial human models of oral, respiratory and intestinal tissue, researchers identified 13 CBD-rich C. sativa extracts which significantly down-regulated the expression of ACE2.

Effects on tissues not stimulated by inflammation

In a model of airway tissues that had not been stimulated by inflammation, Western blot analysis identified six extracts that significantly down-regulated ACE2 expression and two extracts that slightly up-regulated on the rise his expression.

In an unstimulated oral tissue model, two extracts downregulated ACE2 expression, while three other extracts upregulated its expression.

Effects on tissues stimulated by inflammation

Next, the team examined a model of oral tissue that had been stimulated by treatment with inflammatory cytokines, tumor necrosis factor α (TNF-α) and interferon-γ (IFNγ).

RNA sequencing analysis showed that TNFα and IFNγ had upregulated mRNA levels of ACE2 in oral tissue. However, all C. sativa but an extract down-regulated the expression of this level of modified ACE2 mRNA.

Additionally, in a 3D intestinal tissue model stimulated by inflammation, two extracts significantly downregulated ACE2 mRNA levels and in a stimulated airway tissue model, all extracts attenuated the expression of ACE2 induced by TNFα and IFNγ.

“Using 3D artificial human models of oral, respiratory and intestinal tissue, we identified 13 C. sativa extracts that decrease ACE2 protein levels, ”the team writes.

What are the implications of the study?

Researchers say findings provide basis for further analyzes of effects C. sativa may have on the pathogenesis of COVID-19 and other viral diseases where the ACE2 receptor is used as a molecular gateway.

“If these results are further confirmed, these CBD-rich cannabis extracts can be used to develop prevention strategies aimed at lowering ACE2 levels in high-risk passage tissues,” they write.

“Extracts from our most successful CBD-rich novel C. sativa The lines, pending further investigation, may become a useful and safe addition to the prevention and treatment of COVID-19 as an adjunct therapy, ”the team concludes.