Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
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.
About this article: Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER
stress and innate immune responses – Long Chi Nguyen Dongbo Yang Vlad Nicolaescu Thomas J. Best Haley Gula Divyasha Saxena Jon D. Gabbard Shao-Nong Chen Takashi Ohtsuki John Brent Friesen Nir Drayman Adil Mohamed Christopher Dann Diane Silva Lydia Robinson-Mailman Andrea Valdespino Letícia Stock Eva Suárez Krysten A. Jones Saara-Anne Azizi Jennifer K. Demarco William E. Severson Charles D. Anderson James Michael Millis Bryan C. Dickinson Sava Tay Scott A. Oakes Guido F. Pauli Kenneth E. Palmer The National COVID Cohort Collaborative Consortium David O. Meltzer Glenn Randall Marsha Rich Rosner
SCIENCE ADVANCES • 20 Jan 2022 • First Release • DOI: 10.1126/sciadv.abi6110