Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response

Nguyen, Long Chi; Yang, Dongbo; Nicolaescu, Vlad; Best, Thomas J.; Ohtsuki, Takashi; Chen, Shao-Nong; Friesen, J. Brent; Drayman, Nir; Mohamed, Adil; Dann, Christopher; Silva, Diane; Gula, Haley; Jones, Krysten A.; Millis, J. Michael; Dickinson, Bryan C.; Tay, SavaÅŸ; Oakes, Scott A.; Pauli, Guido F.; Meltzer, David O.; Randall, Glenn; Rosner, Marsha Rich

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.