Furthermore, ECS signaling on immune system, viral replication and pathogenesis involve several pathways that mediate the release of cytokines/chemokines through NF- em k /em B, MAPK and JAK-STAT [17,18] or through MNP transcription pathways [6]. still many unknowns regarding COVID-19, but there are also important lessons to be gleaned from AIDS that are applicable to Sulfaquinoxaline sodium salt the COVID-19 pandemic. They are both zoonotic diseases with different mode of transmission, with no vaccine or remedy yet; however, there is an effective antiretroviral therapy for AIDS [5,6]. Furthermore, cannabis and cannabinoids have been proposed and used as adjunctive treatment for AIDS-associated cachexia, and in reduction of disease symptoms [7,8]. The processes of inflammation are important in both the pathogenesis of AIDS and COVID-19 [6,8]. Cannabinoids are effective at suppressing immune and inflammatory functions [7C9], and their potential as an anti-inflammatory treatment in COVID-19 has been suggested [8,9]. As the infection with SARS-CoV-2 causes inflammation due to immune response Sulfaquinoxaline sodium salt and a cytokine storm, resulting in a range of moderate to no symptoms all the way to severe and crucial COVID-19? induced comorbidity and mortality, this Editorial discusses the potential of the pharmacological immune-modulatory effects of cannabinoids that are constituents of the cannabis herb. It is of importance to determine the effects of cannabis and cannabinoid use by those who have not contracted the disease and those who have contracted COVID-19 and the outcomes. ECS components as a potential therapeutic target in COVID-19 The physiological effects of cannabis and cannabinoids are mediated through the human endocannabinoid system (ECS), which consists of cannabinoid receptors (CB1R and CB2R and other candidates), endocannabinoids, and their metabolic enzymes [10]. The ECS is usually widely distributed in almost all human Sulfaquinoxaline sodium salt cells and tissues and involved in the regulation of several functions in mammalian physiology and pathology, and as a gatekeeper in immune homeostasis [11,12]. This common distribution of the ECS is now being exploited as a potential target for cannabinoid-based therapies in numerous disorders including those associated with inflammation and autoimmune dysregulation. Several studies show that cannabis-derived cannabinoids have anti-inflammatory and immunoregulatory properties through the activation of the cannabinoid receptors [13,14]. The role of the ECS as a key regulator of the immune system was examined by Almogi-Hazan and Or, who discussed that this activation of the ECS by cannabis and cannabinoids-based therapeutic regime exerts immune-regulatory properties [14]. This ECS-mediated immunosuppression includes cytokine suppression, inhibition of immune cell proliferation, migration and antibody production, and allows the ECS to exert control of viral pathogenesis [14]. With Rabbit polyclonal to ZFYVE9 a seemingly increasing global acceptance for the use of cannabinoid formulations in medicine [10], it has been hypothesized that cannabinoid receptors [8,9,14] could be therapeutic targets in the COVID-19 pandemic. Therefore, it is of interest to determine whether cannabinoids can quell the inflammatory cytokine release by SARS-Cov-2 and reduce the mortality caused by COVID-19. Quelling the inflammatory cytokine storm in COVID-19 COVID-19 Sulfaquinoxaline sodium salt is usually transmitted by airborne droplets and aerosols, or from fomites into host Sulfaquinoxaline sodium salt cells of infected individuals by using the spike protein to bind onto the ACE2R around the surfaces of human cells [4,8]. The respiratory cells are a gateway into the lungs as ground zero, and lengthen to cells of other organs using ACE2Rs in the throat, heart and blood vessels, kidney, gut, liver?and brain [4,8]. Once inside, these cells replicate the computer virus to produce more SARS-CoV-2, disrupting, provoking and activating immune response. Infected patients may be symptomatic or asymptomatic and the severity of COVID-19 varies with age, genetics, individual exposomes, ethnicity?and pre-existing health status [15,16]. As we have learned more about the high transmission rate of SARS-CoV-2, we have seen that variable moderate symptoms appear between 2?days and 2?weeks after exposure with fever, cough, fatigue, dyspnea, loss of smell and taste, vomiting and diarrhea [4,8,16], and all dependent on the individuals exposome [2]. Genetic differences in an individuals immune system may also be linked to the severity and progression of COVID-19 [4,16]. The severe and critically ill cases develop acute respiratory distress syndrome, characterized by the bodys attempt to defend against the viral invasion with an immune response, with the release of various cytokines such as granulocyte-macrophage colonystimulating factor and IL-6, chemokines and inflammatory mediators [8]. This triggers the inflammatory cytokine.