CBD Versus COVID-19: Are Cannabis Compounds the Cure-All?
CBD Versus COVID-19: Are Cannabis Compounds the Cure-All?
By Kyra Loew
The spread of the COVID-19 pandemic and the rapid rate of mutations impel the search for alternative treatments and an adjuvant to the vaccine. As variants continue to emerge and evade immunity, researchers look to the multifaceted properties of cannabis in hopes of a new drug discovery.
A recent study published in peer-reviewed journal Science Advances by Long Chi Nguyen and 32 other researchers at University of Chicago and University of Louisville reports that high-purity cannabidiol (CBD) and its metabolite inhibit SARS-CoV-2 replication in human lung epithelial cells.
“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,” the study reports.
Before we understand how CBD affects these metabolic processes, let’s briefly examine how the COVID-19 virus infects the body.
SARS-CoV-2 infects host cells by binding to ACE2 receptors through its spike proteins, which are covered in glycans (sugar molecules) that disguise the virus from immune detection. Once fused with the healthy cell, it remodels the internal membrane network and hijacks the mRNA genome, encoding proteins for viral replication. Finally, the host enzyme furin snips at an essential site of five amino acids on the spike proteins, priming further invasion of human cells.
Findings suggest that CBD not only acts in the early phase of preventing infection, but may have a secondary effect on viral protein processing including reversal of viral RNA changes.
Nguyen et al. (2022) conducted in vitro testing that involved treating human lung and monkey kidney cells with high concentrations of CBD for two hours before infecting them with SARS-CoV-2. After 48 hours, they monitored spike protein expression and observed that non-toxic levels of CBD effectively inhibited SARS-CoV-2 replication. This assay included both the original SARS-CoV-2 strain (the cause of COVID-19) and its variants (α, β, and γ); the effects were comparable.
Moreover, while CBD only weakly prevented viral entry, researchers found that CBD was very effective (~95–99%) at inhibiting SARS-CoV-2 spike protein expression at two to six hours following infection, and partially effective (~60%) up to 15 hours after infection. These findings suggest that CBD not only acts in the early phase of preventing infection, but may have a secondary effect on viral protein processing.
The team further backed these suspicions by treating infected cells with CBD for 24 hours and discovered a significant suppression and near complete reversal of viral changes in the host cell RNA. “Together these results suggest that CBD acts to prevent viral protein translation and associated cellular changes.”
A potential mechanism for CBD’s degradation of viral RNA is activation of the interferon signaling pathway. Interferons are cell proteins that act as a primary line of defense against viral infection and replication by signaling the presence of a pathogen. CBD thus suppresses the “cytokine storm” that can be induced at later stages of infection.
The analysis also revealed a significant negative association between CBD and positive COVID tests amongst a cohort of 93,000 patients.
“10% tested positive overall, but only 5.7% of the ~400 who had any cannabinoid in their medical record tested positive. Patients taking CBD versus other cannabinoids had an even lower rate of testing positive (1.2% in 85 CBD patients versus 7.1% in 113 patients taking other cannabinoids).”
As CBD is often extracted within a full-spectrum solution, meaning it contains other cannabinoids such as THC, this study sought to determine if its congenerics could also inhibit Covid-19 replication. However, only CBD and its metabolite (7-OH-CBD–a CBD) displayed potent antiviral effects within a therapeutic range, while the presence of THC attenuated CBD efficacy (1:1).
This finding is interesting as cannabinoids tend to enhance each other’s curative effects, a phenomenon known as the “entourage effect.” But it’s important to note that researchers could not properly test high levels of THC as marijuana remains a controlled substance.
Studies revealed a significant negative association between positive COVID tests and taking prescribed CBD.
In addition to these in vitro testings, the team discovered that a national sample of 1,212 patients taking a prescribed 100mg/ml of oral CBD at the time of their first COVID-19 test reported fewer positive test results than control groups who did not take CBD. This negative association proved even more significant amongst a subgroup of 531 patients, revealing that only 4.9% of patients administered CBD tested positive compared to the 9% in the control group.
These results underscore the potential of high purity, specifically-formulated doses of CBD—rather than commercially available products with CBD additives that vary in quality—to be used as a prophylactic treatment.
Another recent study published in the Journal of Natural Products led by Richard van Breeman and a team of researchers from Oregon State University found cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA—the raw, acidic precursors of CBD and CBG found in hemp—to be equally effective in binding to spike proteins and inhibiting viral entry in human epithelial cells.
These two acidic ligands displayed high binding affinities to the original SARS-CoV-2 and its variants, with CBGA ranked slightly stronger than THCA and CBDA.
“Our infection inhibition assay results clearly indicate that CBDA and CBGA are both able to block cell entry by SARS-CoV-2. The concentrations needed to block infection by 50% of viruses is high but might be clinically achievable,” the study asserts.
These findings highlight support for running clinical trials on cannabinoids in treating or shortening the course of COVID-19 infections.
As van Breeman said in an interview with Vice News, “I think we need combinations of therapies that might include drugs that stop the virus at other points in its lifecycle, but as a weakly active, but nevertheless, effective prevention measure. I think this is a good place to use this dietary supplement.”
It’s important to note that these tests have not yet been conducted in the human body, which involves other complex processes and factors, such as digestion, oxidation, and immune responses, that may yield results that differ from those found in a petri dish. In addition, these studies used high-purity CBD in high amounts typically only found in the FDA-approved Epidiolex solution, rather than commercially available products with CBD additives, where qualities can vary.
While these findings are interesting and help elucidate potential treatments, we advise against viewing CBD as a panacea that replaces other treatments such as the vaccine. For now we acknowledge the potential of these findings as they gateway into clinical trials.
Sources
Carleton, Audrey. “A Q&A With the Scientist Who Discovered Cannabis Can Prevent Covid-19.” VICE, 12 Jan. 2022, https://www.vice.com/en/article/bvn7gd/the-scientist-who-discovered-cannabis-can-prevent-covid-19.
Grandvaux, Nathalie et al. “The interferon antiviral response: from viral invasion to evasion.” Current opinion in infectious diseases vol. 15,3 (2002): 259-67. doi:10.1097/00001432-200206000-00008
https://pubmed.ncbi.nlm.nih.gov/12015460/
Nguyen, Long Chi et al. “Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response.” bioRxiv : the preprint server for biology 2021.03.10.432967. 10 Mar. 2021, doi:10.1101/2021.03.10.432967. Preprint. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987002/
Scudellari, Megan. “How the Coronavirus Infects Cells - and Why Delta Is so Dangerous.” Nature News, Nature Publishing Group, 28 July 2021, https://www.nature.com/articles/d41586-021-02039-y.
van Breemen, Richard B et al. “Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants.” Journal of natural products vol. 85,1 (2022): 176-184. doi:10.1021/acs.jnatprod.1c00946. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768006/
