Cannabidiol (CBD) is a phytocannabinoid with various clinical applications and has proven efficacy for certain medical conditions, along with a favorable safety and tolerability profile [30,31]. Furthermore, unlike ?9-tetrahydrocannabinol (THC), CBD does not induce any psychotropic effects, also making it desirable for therapeutic applications . Cannabinoids can suppress immune activation and inflammatory cytokine production , suggesting their potential for tempering excessive inflammation. Endocannabinoid receptors include CB1 and CB2. CB1 has higher expression in the central nervous system and a lesser expression on peripheral tissues, including the lungs . Airway epithelial cells respond to both CB2 receptor-dependent and independent effects of cannabinoids . CB2 is expressed by varieties of immune cells including circulating lymphocytes, monocytes and tissue mast cells and in lymphoid tissues [33,35]. Activation of CB2 receptor can suppress release of inflammatory IL-1, IL-6, IL-12 and TNF-? . Constitutive production of endocannabinoids occurs by human lung resident macrophages, which is protective in acute and chronic inflammation, mostly via CB2 receptors . Importantly, human lung resident macrophages also express both CB1 and CB2 receptors . Agonists of CB2 have been shown to inhibit TNF-? from CD14+ monocytes and M1 macrophages, and increase expression of anti-inflammatory cytokine IL-10 . CB2 agonists also induce anti-inflammatory FoxP3+ regulatory T-cells (Tregs) which produce TGF-? and IL-10 . In addition, CBD has been shown to induce the differentiation of functional immunosupressive Tregs . In murine models of lung injury, CBD reduced lipopolysaccharide (LPS)-induced acute pulmonary inflammation [41,42]. In rat models of experimental asthma, CBD treatment reduced airway inflammation, as well as levels of serum IL-4, IL-5, IL-13, IL-6 and TNF-?, which are implicated in airway inflammation and fibrosis in asthma [43,44]. Moreover, CBD was able to directly suppress T-cell secretion of IL-1 and IFN? . In piglets with hypoxic-ischemic lung damage, CBD reduced histologic damage, decreased leukocyte infiltration and modulated IL-1 concentration in bronchoalveolar lavage fluid , while in a rat model of sepsis, CBD reversed oxidative stress and reduced mortality . In humans, cannabinoid use prevented induction of pro-inflammatory CD16+ monocytes and production of IP-10, suggesting anti-inflammatory effects in humans . In another human study, in addition to reduction of pro-inflammatory monocytes, heavy cannabis use was also associated with decreased frequencies of HLA-DR+CD38+ activated CD4 and CD8 T-cells and frequencies of IL-10, IL-12 and TNF-? -producing antigen presenting cells compared to non-cannabis users . The anti-inflammatory effects of cannabinoids are now under investigation in clinical trials, as such, our team in now conducting a clinical trial in the context of HIV infection . Therefore, as SARS-CoV2 induces significant damage through pro-inflammatory cytokine storm mediated by macrophages and other immune cells and based on the fact that CBD has broad anti-inflammatory properties, CBD might represent as a potential anti-inflammatory therapeutic approach against SARS-CoV2-induced inflammation. In this regard, first a deeper understanding of the specific effects of SARS-CoV2 on human macrophages and T-cell physiology and immunological functions is needed. As CBD is already a therapeutic agent used in clinical medicine and has a favorable safety profile, the results of in vitro and animal model proof-of-concept studies would provide the necessary supporting evidence required before embarking on costly and labor-intensive clinical trials.