Figure: CBD improved the symptoms of Poly(I:C)‐induced ARDS and normalized the expression level of apelin in the blood. Intranasal administration of poly(I:C) demonstrated a reduction in the blood T cells while increased the neutrophils compared with the sham control group (dot plot flow cytometry panels). Further, intranasal poly(I:C) reduced apelin expression in whole blood of mice (Histogram and bargraph panels), as assessed by flow cytometry. Administration of CBD attenuated these effects. The bargraphs are representing the average of values for 10 mice per group (**P < .03)

Évila Lopes Salles 1 2Hesam Khodadadi 1 2Abbas Jarrahi 3Meenakshi Ahluwalia 4Valdemar Antonio Paffaro Jr 5Vincenzo Costigliola 6Jack C Yu 7David C Hess 8Krishnan M Dhandapani 3Babak Baban 1 2 8

Considering lack of target-specific antiviral treatment and vaccination for COVID-19, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve COVID-19-infected patient outcomes. In a follow-up study to our recent findings indicating the potential of Cannabidiol (CBD) in the treatment of acute respiratory distress syndrome (ARDS), here we show for the first time that CBD may ameliorate the symptoms of ARDS through up-regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system. By administering intranasal Poly (I:C), a synthetic viral dsRNA, while we were able to mimic the symptoms of ARDS in a murine model, interestingly, there was a significant decrease in the expression of apelin in both blood and lung tissues. CBD treatment was able to reverse the symptoms of ARDS towards a normal level. Importantly, CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID-19 and many other pathologic conditions.

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