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

Sci Adv. 2022 Feb 25;8(8):eabi6110. doi: 10.1126/sciadv.abi6110. Epub 2022 Feb 23.

Abstract

The spread of SARS-CoV-2 and ongoing 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 IRE1α RNase 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 use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • COVID-19 / drug therapy
  • COVID-19 / virology
  • Cannabidiol / chemistry
  • Cannabidiol / metabolism
  • Cannabidiol / pharmacology*
  • Chlorocebus aethiops
  • Endoplasmic Reticulum Stress / drug effects
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Epithelial Cells / virology
  • Female
  • Gene Expression Regulation, Viral / drug effects
  • Host-Pathogen Interactions / drug effects*
  • Host-Pathogen Interactions / physiology
  • Humans
  • Immunity, Innate / drug effects*
  • Interferons / metabolism
  • Mice
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / physiology
  • Vero Cells
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Cannabidiol
  • Interferons
  • ERN1 protein, human
  • Protein Serine-Threonine Kinases
  • Endoribonucleases