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cbd and viruses

“Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2,” the researchers wrote in an abstract of the study.

CBGA and CBDA prevented infection from the virus that causes Covid-19 by binding to its . [+] characteristic spike protein.

The Making Of New York’s $150 Million ‘Cannabis Campus’

Although further research is needed, van Breemen noted that study shows the cannabinoids could be developed into drugs to prevent or treat Covid-19.

The Feds Are Coming For Delta-8 THC

Compounds in cannabis can prevent infection by the virus that causes Covid-19, according to research . [+] published this week.

But if a clinical trial of the compound as a preventative for coronavirus infections is successful, “due to the fact that NT-VRL terpenes are also found in cannabis strains, it can be estimated that cannabis evaporation will also have some effectiveness,” says Eyal.

Terpenes have shown the potential to treat a wide variety of viral infections in many in vitro studies, and research released by Eybna last year found that NT-VRL combined with cannabidiol (CBD) showed promise as a treatment for the severe inflammatory response seen in many Covid-19 patients known as a cytokine storm.

Portrait of Female Doctor Holding CBD Oil Drops.

The Feds Are Coming For Delta-8 THC

When asked in a virtual interview if the potential for NT-VRL inhalation to be used as a preventative for coronavirus infections suggests that smoking or vaping cannabis could have a similar effect, Eybna CEO and co-founder Nadav Eyal notes that it “is important to be careful to not jump to conclusions of this kind.”

A combination of compounds found in cannabis showed the potential to treat or even prevent coronavirus infections in human lung cells, according to recently published research. The study, “In Vitro Evaluation of the Activity of Terpenes and Cannabidiol against Human Coronavirus E229,” was published by the peer-reviewed journal Life on March 29.

The Making Of New York’s $150 Million ‘Cannabis Campus’

Additional research was conducted by Eybna and pre-clinical contract research organization Pharmaseed to evaluate the antiviral properties of NT-VRL with and without CBD against the human coronavirus strain HCoV-229E. Although not the strain of coronavirus that causes Covid-19 (SARS-CoV-2), the less virulent HCoV-229E is associated with various respiratory illnesses ranging from the common cold to severe pneumonia and is considered a good alternative for preliminary research.

Cannabis technology firm Eybna is studying the effectiveness of a proprietary terpene formulation . [+] and CBD in the prevention and treatment of coronavirus infections.

Cbd and viruses

National Institutes of Health grant R01 AI137514 (G.R.)

CBD could be acting to block viral entry to host cells or at later steps following infection. As CBD was shown to decrease ACE2 expression in some epithelial cells including A549 ( 16 ), we first determined whether CBD suppressed the SARS-CoV-2 receptor in our A549-ACE2 overexpressing cells. No decrease in ACE2 expression was observed ( Fig. 3A ). Furthermore, analysis of lentiviruses pseudotyped with either the SARS-CoV-2 spike protein or the VSV glycoprotein ( 17 ) showed that antibody to the spike protein effectively blocked viral infection of the SARS-CoV-2, but not VSV-G expressing viruses. However, 10 μM CBD only partially inhibited cell entry by spike-expressing virus, suggesting that other mechanisms were largely responsible for its antiviral effects ( Fig. 3B , and figs. S3 A and B). By contrast, antibodies to the spike protein effectively blocked viral infection of the SARS-CoV-2 but not VSV-G expressing viruses. Consistent with this, CBD was also effective at inhibiting SARS-CoV-2 spike protein expression in host cells even 2 hours after infection in the presence of antibodies to the spike protein to prevent reinfection during this time period ( Fig. 3C , ​ ,D). D ). To assess whether CBD might be preventing viral protein processing by the viral proteases Mpro or PLpro, we assayed their activity in vitro (fig. S4). CBD did not affect the activity of either protease, raising the possibility that CBD targets host cell processes.

Associations between reported cannabinoid medication use and COVID-19 test results among adults tested at the University of Chicago Medicine (total n=93,565). P*: p-values of percent positivity of the specified patient population compared to percent positivity of all patients (10% COVID-19 positive among 93,565 patients). Middle right: 85 patients took CBD before their COVID test date. Upper right: 82 of the 85 patients took FDA-approved CBD (Epidiolex ® ) and were matched to 82 of the 93,167 patients (Matched Controls) with a nearest neighbor propensity score model that scored patients according to their demographics and their recorded diagnoses and medications from the two years before their COVID-19 test. P-values were calculated using Fisher’s exact test two-sided.

(A) A549 cells with ACE2 overexpression (A549-ACE2) were treated with indicated doses of CBD, KPT-9274, or URMC-099 followed by infection with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. EC50 values are indicated. (B) The 1 H qNMR spectra of CBD from a reference material and CBD samples from three different suppliers A, B, and C. (C) A549-ACE2 cells were treated with indicated doses of CBD from three different suppliers followed by infection with SARS-CoV-2 at an MOI of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. EC50 values are indicated.

Funding:

The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARSCoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. 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.

CBD is rapidly metabolized in the liver and gut into two main metabolites, 7-carboxy-cannabidiol (7-COOH-CBD) and 7-hydroxy-cannabidiol (7-OH-CBD). Although the levels of 7-COOH-CBD are 40-fold higher than 7-OH-CBD in human plasma, 7-OHCBD is the active ingredient for the treatment of epilepsy ( 14 ). Like CBD but unlike the other cannabinoids, 7-OH-CBD effectively inhibited SARS-CoV-2 replication in A549-ACE2 cells (EC50 3.6 μM; Fig. 2C ) and was non-toxic to cells (fig. S2H). Analysis of blood plasma levels in healthy patients taking FDA-approved CBD (Epidiolex ® ) shows a maximal concentration (Cmax) for CBD in the nM range whereas 7-OH-CBD had a Cmax in the μM range, similar to that observed in cultured cells ( 15 ). These results suggest that CBD itself is not present at the levels needed to effectively inhibit SARS-CoV-2 in people. By contrast, the plasma concentrations of its metabolite 7-OH-CBD, whose Cmax can be increased several-fold by co-administration of CBD with a high-fat meal, are sufficient to potentially inhibit SARS-CoV-2 infection in humans ( 15 ).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), a pandemic that has overtaken the world during the past year. SARS-CoV-2, related to severe acute respiratory syndrome-related coronavirus (SARS-CoV), is the seventh species of coronavirus known to infect people. These coronaviruses, which include SARS-CoV, 229E, NL63, OC43, HKU1, and MERS-CoV cause a range of symptoms from the common cold to more severe pathologies ( 1 ). Despite recent vaccine availability, SARS-CoV-2 is still spreading rapidly ( 2 ), highlighting the need for alternative treatments, especially for populations with limited access to vaccines. To date, few therapies have been identified that block SARS-CoV-2 replication and viral production.

DISCUSSION

(A) Immunoblots of ACE2 protein expression from A549-ACE2 cell lysates either untreated or treated with vehicle or CBD at indicated doses (n=3). Blots were probed with antibodies against ACE2 and tubulin. ACE2 protein expression levels were normalized to the tubulin signal within each sample. ACE2 expression levels were plotted relative to untreated samples. Expression levels were compared to vehicle by one-way ANOVA. (B) 293T-ACE2 cells were infected by spike or VSV-G pseudovirus for 72 hours with the indicated doses of CBD treatment, and the percentage of infected cells plotted. (C) A549-ACE2 cells were either pre-treated or not with 10 μM CBD for 2 hours, then infected with SARS-CoV-2 at an MOI of 0.5 for 2 hours. Cells were then treated with 10 μM CBD or DMSO for 16 hours with the spike neutralizing antibody to prevent reinfection. Spike positive cells were quantified and normalized to the virus-infected only sample. (D) Validation of neutralizing antibody efficacy. 400 pfu of SARS-CoV-2 virus was incubated with or without 100 μM of neutralizing antibody for 1 hour. A549-ACE2 cells were treated with the mixture for 16 hours and Spike positive cells were quantified.

National Institutes of Health grant R01 AI134980 (G.R.)