In quest of a new therapeutic approach in COVID-19: the endocannabinoid system

Abstract

The SARS-Cov-2 virus caused a high morbidity and mortality rate disease, that is the COVID-19 pandemic. Despite the unprecedented research interest in this field, the lack of specific treatments leads to severe complications in a high number of cases. Current treatment includes antivirals, corticosteroids, immunoglobulins, antimalarials, interleukin-6 inhibitors, anti-GM-CSF, convalescent plasma, immunotherapy, antibiotics, circulation support, oxygen therapy, and circulation support. Due to the limited results, until specific treatments are available, other therapeutic approaches need to be considered. The endocannabinoid system is found in multiple systems within the human body, including the immune system. Its activation can lead to beneficial results such as decreased viral entry, decreased viral replication, and a decrease in pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α, or IFN-γ. Moreover, endocannabinoid system activation can lead to an increase in anti-inflammatory cytokines, mainly represented by IL-10. Overall, the cannabinoid system can potentially reduce pulmonary inflammation, increase the immunomodulatory effect, decrease PMN infiltration, reduce fibrosis, and decrease viral replication, as well as decrease the ‘cytokine storm’. Although the cannabinoid system has many mechanisms to provide certain benefits in the treatment of SARS-CoV-2 infected patients, research in this field is needed for a better understanding of the cannabinoid impact in this situation.

Scientific Evaluation of Dhuma Yoga (An Ayurvedic Fumigation Medicine) as Preventive and Curative on Symptoms of Covid-19 Disease

“…Overall, the cannabinoid system can potentially reduce pulmonary inflammation, increase the immuno-modulatory effect, decrease PMN infiltration, reduce fibrosis, and decrease viral replication, as well as decrease the cytokine storm. [32] In an in vitro study Cannabis compounds Viz. CBD, CBG and THCV exhibited anti-inflammatory activity in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages.…”

“…Proinflammatory cytokines like interleukins, TNF-α and TNF-γ that are involved in the inflammation of alveoli and damage the lungs can be controlled by activating the endocannabinoid system through Vijaya (Cannabis sativa Linn.). [32] In vitro experiment with CBD (cannabidiol), a major phytocannabinoid was effective in stopping the replication of SARS-CoV-2 in lung epithelial cells. [35] CBD (cannabidiol) is a known anti-inflammatory and immune modulator molecule.…”

Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review

“…Therefore, the study of cannabinoids as probable therapeutics during infection of SARS-CoV-2 has been reviewed, mainly illuminating their effects on inhibition of excessive cytokine secretion followed by anti-inflammatory amelioration [ 165 , 166 , 167 , 168 , 169 , 170 , 171 ]. A significant number of studies demonstrate that the anti-inflammatory activities of cannabinoids are characterized by a number of pathways such as the regulation of production, migration and functional ability of immune cells (macrophages, monocytes, neutrophils, lymphocytes, dendritic cells, killer cells, fibroblasts and endothelial cells), reduction of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12, IL-17, IL-18, IFN-γ, TNF-α, MCP-1/CCL5, GM-CSF) and increase of anti-inflammatory cytokines (IL-4, IL-10, IL-11, TGF-β) [ 21 , 154 ]. Since some contradictions exist in the literature [ 172 , 173 , 174 ], effects of cannabinoids on cytokine release are still arguable.…”

The Endocannabinoid System as Prognostic Biomarker of the Obstructive Sleep Apnea Morbidity in COVID-19-Recovered Individuals

“…Although the role of the endocannabinoid system in the sleep control has been studied in recent years, there are several gaps that will require further focus, including the characterization of the molecular mechanisms of action by which the endocannabinoids regulate the neurobiological networks linked to the sleep disturbances. Moreover, the lack of evidence suggesting the disruption of the functioning of the endocannabinoid system either during the SARS-CoV-2 infection or after recovery of COVID-19 is limited; however, recent evidence has suggested a likely involvement of the CB 2 cannabinoid receptor and COVID-19 [ 63 – 66 ]. Whether additional members of the endocannabinoid system, such as AEA, 2-AG, or FAAH, FAAH, DAGL, MAGL and, AMT, might be affected in post-COVID-19 disease, remains to be determined.…”