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0 0.5 1 1.5 2+ Case 50% Improvement Relative Risk Case (b) 33% Cannabidiol for COVID-19  Nguyen et al.  Prophylaxis Does cannabidiol reduce COVID-19 infections? Retrospective 2,424 patients in the USA Fewer cases with cannabidiol (p=0.006) Nguyen et al., Science Advances, January 2022 Favors cannabidiol Favors control

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

Nguyen et al., Science Advances, doi:10.1126/sciadv.abi6110 (date from preprint)
Jan 2022  
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Retrospective 1,212 patients in the USA with a history of seizure-related conditions, showing patients treated with CBD100 had significantly lower incidence of COVID-19 cases compared to a matched control group.
In Vitro study showing CBD inhibits SARS-CoV-2 with Vero E6 and Calu-3 cells. Mouse study showing CBD significantly inhibited viral replication in the lung and nasal turbinate.
Authors note that CBD does not inhibit ACE2 expression or the main viral proteases, inhibition occurs after viral entry. Authors stress several limitations for use at this time, including purity, quality, and the formulation of products, and potential lung damage based on administration method.
Authors recommend clinical trials, but do not mention the existing RCT by Crippa et al.
risk of case, 49.6% lower, RR 0.50, p = 0.006, treatment 26 of 531 (4.9%), control 48 of 531 (9.0%), NNT 24, odds ratio converted to relative risk, active CBD100 users.
risk of case, 32.9% lower, RR 0.67, p = 0.009, treatment 75 of 1,212 (6.2%), control 108 of 1,212 (8.9%), NNT 37, odds ratio converted to relative risk, all CBD100 users.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Nguyen et al., 20 Jan 2022, retrospective, USA, peer-reviewed, 34 authors.
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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, Savaş Tay, Scott A Oakes, Guido F Pauli, Kenneth E Palmer, The National COVID Cohort Collaborative Consortium, David O Meltzer, Glenn Randall, Marsha Rich Rosner
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 IRE1 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.
SUPPLEMENTARY MATERIALS Supplementary material for this article is available at sciadv.abi6110 View/request a protocol for this paper from Bio-protocol. Teaser: Cannabidiol from the cannabis plant has potential to prevent and inhibit SARS-CoV-2 infection. of 18 National COVID Cohort Collaborative (N3C). The patient data analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave and supported by NCATS U24 TR002306. This research was possible because of the patients whose information is included within the data from participating organizations ( and the organizations ( resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the on-going development of this community resource (28) . The project described was supported by the National Institute of General Medical Sciences, 5U54GM104942-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The analysis used only de-identified data (i.e., N3C Data Access Tier 2, described at We gratefully acknowledge contributions from the following N3C core teams: of 18 • Additional N3C acknowledgments. We would also like to thank others not listed above: Joy Alamgir (ARIScience), Seth Russell, MS (University of Colorado),..
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