Commentary: Use of Cannabinoids to Treat Acute Respiratory Distress Syndrome and Cytokine Storm Associated With Coronavirus Disease-2019

We read with great interest the recent opinion by Nagarkatti et al. (2020), highlighting a potential role of cannabinoids in the treatment of acute respiratory distress syndrome (ARDS) associated with COVID-19.In particular, based on their previous studies evaluating the effect of THC in ARDS animal models, they focused the attention on the cannabinoid receptors targeting to control the hyperimmune response in severe COVID-19.Although cannabinoids and CBD in particular show an interesting potential, important issues concerning this therapeutics must be considered.In recent months, the pressing need for effective treatments to counteract the spread of the COVID-19 pandemic dictated the development of new therapeutic approaches to handle or possibly prevent the complications of SARS-CoV-2 infections as a worldwide priority.Clinical profiles of COVID-19 patients range from asymptomatic infection to severe pneumonia with multisystem failure, the leading cause of mortality.In patients with severe disease, the occurrence of cytokine storm and a state of hyperinflammation led to acute respiratory distress syndrome (ARDS) (Lotfi and Rezaei, 2020).As Nagarkatti and colleagues (2020) highlighted, the potential use of cannabinoids in COVID-19 has been suggested for their immunomodulatory and anti-inflammatory properties, but not for the direct antiviral activity.Several authors focused the attention on the nonpsychoactive CBD as adjuvant in SARS-CoV-2 therapy.Recently, for the first time, it has been reported that CBD is able to reduce pro-inflammatory cytokine levels ameliorating symptoms of ARDS induced in a murine model (Khodadadi et al., 2020).Moreover, CBD seems to down-regulate the expression of ACE2 and TMPRSS2, two receptors exploited by SARS-CoV-2 to enter the cells (Wang et al., 2020).However, further studies to support CBD-mediated regulation of ACE2 and TMPRSS2 are needed.Despite the encouraging potential of CBD, in our opinion, the first issue to consider is that, to date, there are no clinical data about the optimal anti-inflammatory dose and regimen of CBD in patients.