Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
Our results suggest that CBD can block SARS-CoV-2 infection at early stages of infection, and CBD administration is associated with a lower risk of SARS-CoV-2 infection in humans. Furthermore, the active compound in patients is likely to be 7-OH-CBD, the same metabolite implicated in CBD treatment of epilepsy. The substantial reduction in SARS-CoV-2 infection risk of approximately an order of magnitude in patients who took FDA-approved CBD highlights the potential efficacy of this drug in combating SARS-CoV-2 infection. Finally, the ability of CBD to inhibit replication of MHV raises the possibility that CBD may have efficacy against new pathogenic viruses arising in the future.
One mechanism contributing to the antiviral activity of CBD is the induction of the interferon pathway both directly and indirectly following activation of the host immune response to the viral pathogen. In fact, interferons have been tested clinically as potential treatments for COVID-19 (21). Importantly, CBD also suppresses cytokine activation in response to viral infection, reducing the likelihood of immune cell recruitment and subsequent cytokine storms within the lungs and other affected tissues. These results complement previous findings suggesting that CBD suppresses cytokine production in recruited immune cells such as macrophages (22). Thus, CBD has to 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.
CBD has a number of advantages as a potential preventative agent against SARS-CoV-2. CBD is widely available without restricted access if the content of THC is <0.3%. There are multiple means of ingestion, including potential for inhalation and nasal delivery. CBD blocks viral replication after entry into cells and, thus, is likely to be effective against viral variants with mutant spike proteins. Unlike drugs such as remdesivir or antiviral antibodies, CBD administration does not require injection in hospital settings. Finally, CBD is associated with only minor side effects (15).
However, several issues require close examination before CBD can be considered or even explored as a therapeutic for COVID-19 (11). Although many CBD formulations are available on the market, they vary vastly in quality, the amount of CBD, and their pharmacokinetic properties after oral administration, which are mostly unknown. CBD is quite hydrophobic and forms large micellar structures that are trapped and broken down in the liver, thereby limiting the amount of drug available to other tissues after oral administration. The inactive carriers have a significant impact on clinically obtainable concentrations. As CBD is widely sold as a preparation in an edible oil, we analyzed flavored commercial hemp oils and found a CBD content of only 0.30% in a representative sample (fig. S12). The purity of CBD and, in particular, the composition of the materials labelled as CBD are also important, especially in light of our findings suggesting that other cannabinoids such as THC might act to counter CBD antiviral efficacy. This essentially eliminates the feasibility of marijuana serving as an effective source of antiviral CBD, in addition to issues related to its legal status. Finally, other means of CBD administration such as vaping and smoking raise concerns about potential lung damage.
Future studies to explore the optimal means of CBD delivery to patients along with clinical trials will be needed to fully test the promise of CBD as a therapeutic to block SARS-CoV-2 infection. As the clearance rates for CBD in plasma are substantially lower in humans than mice, we would suggest moving to clinical trials rather than doing preclinical studies in animal models (15). 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 necessary human in vivo concentration and optimal route and formulation remain to be defined. We strongly caution against the urge to take CBD in presently available formulations as a preventative or treatment therapy at this time, especially without the knowledge of a rigorous randomized clinical trial with this natural product (23).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987002/