Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
Nguyen, Long Chi Yang, Dongbo Nicolaescu, Vlad Best, Thomas J. Randall, Glenn Rosner, Marsha Rich National COVID Cohort Collaborative Consortium
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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 IRE1alpha 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.
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Nguyen LC, Yang D, Nicolaescu V, Best TJ, Gula H, Saxena D, Gabbard JD, Chen SN, Ohtsuki T, Friesen JB, Drayman N, Mohamed A, Dann C, Silva D, Robinson-Mailman L, Valdespino A, Stock L, Suárez E, Jones KA, Azizi SA, Demarco JK, Severson WE, Anderson CD, Millis JM, Dickinson BC, Tay S, Oakes SA, Pauli GF, Palmer KE; National COVID Cohort Collaborative Consortium, Meltzer DO, Randall G, Rosner MR. 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. PMID: 35050692.. Link to article on publisher's site
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The UMass Center for Clinical and Translational Science (UMCCTS), UL1TR001453, helped fund this study.
Full author list omitted for brevity. For the full list of authors, see article.