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Madeline Colli is the Associate Editor for Cannabis Patient Care and Cannabis Science and Technology magazines at MJH Life Sciences.
Recently, researchers performed a study which discovered that a cannabis plant compound inhibited COVID-19 infection in human lung cells.
Researchers in the US recently conducted a study which disclosed that a cannabis plant compound inhibited infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human lung cells. SARS-CoV-2 is the virus that causes COVID-19, threatening global health and world economies (1,2). Marsha Rosner, PhD (3), and other colleagues from the University of Chicago (Chicago, Illinois) discovered that cannabidiol (CBD) and its metabolite 7-OH-CBD potently blocked SARS-CoV-2 replication in lung epithelial cells.
Through the combination of CBD and 7-OH-CBD, the expression of certain genes within the viral cells were inhibited and changes in gene expression within the lung cells that resulted from the presence of COVID-19 were reversed (4). Thus, CBD and 7-OH-CBD serve in both protective and therapeutic roles. CBD was also found to have the ability to block viral ribonucleic acid (RNA), including the coding for the spike protein, which is the tool the virus uses to enter our cells. “This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection,” said Rosner and the team (1).
Even with recently approved vaccines being rolled out in many countries, the virus continues to spread rapidly, heightened by more-transmissible variants such as the B.1.1.7 variant. Rosner and her colleagues say that this highlights the need for alternative approaches, especially among populations with limited access to vaccines. Few therapies to date have been identified as being able to block SARS-CoV-2 replication and viral reproduction.
Primarily, the SARS-CoV-2 virus enters host cells through the binding of a surface viral protein—called spike protein— to the human host cell receptor angiotensin-converting enzyme 2 (ACE2). From there, the viral genome is then translated into two large polypeptides that are severed by the viral proteases main protease (MPro) and papain-like protease (PLPro) to produce the proteins necessary for viral replication, assembly, and budding (1).
To analyze the effect of CBD on SARS-CoV-2 replication, the researchers pretreated A549 human lung carcinoma cells expressing ACE-2 (A549-ACE2) with 0-10 μM CBD for 2 hours before infecting them with SARS-CoV-2. Evaluation of the cells 48 hours later expressed CBD had potently inhibited viral replication in the cells. When CBD was assessed to possibly prevent proteolytic cleavage by MPro and PLPro, it was observed that CBD had no effect on the activity of either protease. This revelation led the team to hypothesize that CBD targets host cell processes. Consistent with their hypothesis, RNA sequencing of infected A549-ACE2 cells treated with CBD for 24 hours showed significant suppression of SARS-CoV-2-induced changes in gene expression. CBD was shown to have effectively eliminated viral RNA expression, which included RNA coding for the spike protein. It was also found that both SARS-CoV-2 and CBD triggered significant changes in cellular gene expression, such as the expression of several transcription factors. Further analysis of host cell RNA expressed that the virus-induced changes were almost completely reversed, though rather than the cells returning to a normal cell state, the CBD plus virus-infected cells resembled those treated with CBD alone.
Another critical finding researchers discovered was that CBD had “effectively reversed” the triggering of a hyperinflammatory response, also known as a “cytokine storm” which is brought on by the presence of the virus, restoring cells not to a previral level of inflation, but a state as if the cells had been treated with only CBD. A study completed near the end of 2020 by the Dental College of Georgia (DCG) (Augusta, Georgia) and the Medical College of Georgia (Augusta, Georgia) also had similar findings to the team from the University of Chicago (5). Cytokine storms have been one of the principal causes of death resulting from a COVID-19 infection. CBD was identified in reducing damage in the lungs spurred by cytokine storms caused from COVID-19 by normalizing levels of apelin, a peptide known to reduce inflammation, decreasing physical lung damage associated with adult respiratory distress syndrome (ARDS), and improving oxygen levels. During a COVID-19 infection, these apelin levels were seen to be at very low levels. Rosner and her team stated that “CBD has the potential not only to act as an antiviral agent at early stages of infection but also to protect the host against an overactive immune system at later stages,” (1).
During the University of Chicago’s study, a range if other cannabinoids were also tested, but by the end of the trial, CBD was the only cannabinoid found to have any effect at all on COVID-19-infected cells. Limited-to-no antiviral activity was exhibited by the other cannabinoids investigated. CBD is often consumed as part of a Cannabis Sativa extract, which is also what led the team to consider investigating other cannabinoids with closely related structures to see if they would reveal similar or stronger results. The team hopes that CBD will continue to be investigated as a potential COVID-19 treatment following the research from their article about the study, which is currently under peer-review. “We advocate carefully designed placebo-controlled clinical trials with known concentrations and highly-characterized formulations in order to define CBD’s role in preventing and treating early SARS-CoV-2 infection,” the authors stated (4). Even with these impressive scientific breakthroughs, more is still needed to be researched on the medicinal properties of the cannabis plant and how it can be used to fight the global coronavirus pandemic.