COVID-19 (SARS-CoV-2) causes multiple inflammatory complications, resulting not only in severe lung inflammation but also harm to other organs . Although the current focus is on the management of acute COVID-19, there is growing concern about long-term effects of COVID-19 (Long Covid), such as fibroproliferative changes in the lung, heart and kidney . Therefore, the identification of therapeutic targets not only for the management of acute COVID-19 but also for preventing Long Covid are needed, and would mitigate against long-lasting health burden and economic costs, in addition to saving lives . COVID-19 induces pathological changes via multiple pathways, which could be targeted simultaneously for optimal effect . We discuss the potential pathologic function of increased activity of the endocannabinoid/CB1 receptor system and inducible NO synthase (iNOS). We advocate a polypharmacology approach, wherein a single chemical entity simultaneously interacts with CB1 receptors and iNOS causing inhibition, as a potential therapeutic strategy for COVID-19-related health complications.