Abstract: International Journal of Molecular Sciences Review Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19 † Barbara Malinowska 1, *,‡ , Marta Baranowska-Kuczko 1,2,‡ , Aleksandra Kicman 1 and Eberhard Schlicker 3, * 1 2 3 * † ‡ Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, Poland; mabar@umb.edu.pl (M.B.-K.); olakicman@gmail.com (A.K.) Department of Clinical Pharmacy, Medical University of Białystok, 15-222 Białystok, Poland Department of Pharmacology and Toxicology, University of Bonn, 53127 Bonn, Germany Correspondence: bmalin@umb.edu.pl (B.M.); e.schlicker@uni-bonn.de (E.S.); Tel.: +48-85-748-5699 (B.M.) To the memory of our friend Professor Daniel Moura (Department of Pharmacology, University of Porto, Portugal), who was scientifically active in the field of ACE2 and angiotensin II. These authors contributed equally to this work. ijms22041986 Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with ∆9 -tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19. Academic Editor: William C. Keywords: ACE2; cannabidiol; COVID-19; SARS-CoV-2; respiratory disease



 Citation: Malinowska, B.; Baranowska-Kuczko, M.; Kicman, A.; Schlicker, E. Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19 †. Int. J. Mol. Sci. 2021, 22, 1986. https://doi.org/10.3390/ (Trey) Putnam Received: 11 January 2021 Accepted: 12 February 2021