Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ongoing coronavirus disease 2019 (COVID-19) pandemic underscores the need for new treatments. Here, we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1 alpha ribonuclease endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against current use of non-medical formulations as a preventative or treatment therapy.

Automated summary

This study found that cannabidiol (CBD) can inhibit the infection of SARS-CoV-2 in cells and mice, potentially making it a preventative agent for early-stage SARS-CoV-2 infection. The study also discovered that CBD inhibits SARS-CoV-2 replication partially by regulating the host cell's endoplasmic reticulum stress response and interferon signaling pathways. However, the current use of non-medical formulations for prevention or treatment is not recommended.