cbd and cytokine storm

Anti-inflammatory effect of CBD after…

Introduction: In the absence of effective antivirals and vaccination, the pandemic of COVID-19 remains the most significant challenge to our health care system in decades. There is an urgent need for definitive therapeutic intervention. Clinical reports indicate that the cytokine storm associated with acute respiratory distress syndrome (ARDS) is the leading cause of mortality in severe cases of some respiratory viral infections, including COVID-19. In recent years, cannabinoids have been investigated extensively due to their potential effects on the human body. Among all cannabinoids, cannabidiol (CBD) has demonstrated potent anti-inflammatory effects in a variety of pathological conditions. Therefore, it is logical to explore whether CBD can reduce the cytokine storm and treat ARDS. Materials and Methods: In this study, we show that intranasal application of Poly(I:C), a synthetic analogue of viral double-stranded RNA, simulated symptoms of severe viral infections inducing signs of ARDS and cytokine storm. Discussion: The administration of CBD downregulated the level of proinflammatory cytokines and ameliorated the clinical symptoms of Poly I:C-induced ARDS. Conclusion: Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.

CBD improves lung structure and…

Keywords: ARDS; CBD; COVID-19; cannabidiol; cytokine storm; inflammation.

Conflict of interest statement

Copyright 2020, Mary Ann Liebert, Inc., publishers.

No competing financial interests exist.

CBD improves lung structure and function after intranasal Poly(I:C) treatment. (A) Blood oxygen…

Figures

Anti-inflammatory effect of CBD after intranasal Poly(I:C) treatment. (A, B) Flow cytometry analysis…

Although it hasn’t yet been peer-reviewed, it’s worth noting that a preprint study led by University of Chicago researchers released in March found similarly positive results when treating ARDS-induced mice with CBD. If it successfully gets through peer review, it will be another piece of evidence indicating CBD could be effective in treating cytokine storms and ARDS.

Baban explains it using an analogy about police and a “bad guy.” The bad guy has broken in somewhere and the cytokines are calling for backup. “The place is surrounded by police in SWAT gear and still they’re calling for more and more backup — when what you actually need is to step back and diffuse the situation,” Baban says.

All of the researchers Inverse interviewed for this story stressed two things: first, that CBD is a very promising treatment for cytokine storms and ARDS and second, more research and clinical trials should be done before using it as a treatment in humans.

Here’s what happens when someone is infected with the SARS-C0V-2 virus, but is asymptomatic or has mild Covid: Macrophages race to the virus and gobble it up. Recognizing that this is something the body hasn’t seen before and will need help fighting, it presents the antigens to T-cells. B-cells make warning labels to stick on the virus antibodies, so other cells can identify and destroy it.

Enter: The endocannabinoid system

How did they do it? The researchers in Canada, took 3D printed artificial skin and exposed it to UV light to induce inflammation. After inducing inflammation, the researchers treated the artificial skin with seven different cannabis “cultivars.” Medical cannabis researchers typically refer to different phytocannabinoid and terpene (aromatic oils found in the cannabis plant that can have their own medicinal properties) combinations as “cultivars,” not strains.

The endocannabinoid system’s job is to help the body maintain a state of homeostasis, explains Bonni Goldstein, a physician in California and expert in cannabis medicine who consults with cannabis industry leaders. All mammals have an endocannabinoid system, and in turn, this system balances the “chemical messages that our cells send to each other,” Goldstein tells Inverse.

“We don’t have very many good treatments for viruses,” Baban tells Inverse. “Not like we do for infections.”

How do cytokine storms work?

“Apelin is widely presented in the lungs, heart, and digestive system,” Baban explains, “and can be important for homeostasis and rebalancing the immune system.”

When immunologist Babak Baban found out which side effects were responsible for the most severe cases of Covid-19, he immediately thought about cannabis.

Cbd and cytokine storm

Present findings propose a potential immunotherapeutic role for CBD in the treatment of severe respiratory viral infections and ARDS. The current data support the notion that the anti-inflammatory function of CBD may reduce cytokine storm and mitigate the effects of exaggerated inflammation. Recent reports suggest that the interaction between immune system and COVID-19 is a two-phased process of immune activation and immune dysregulation. Increasingly, clinical and preclinical studies show regulatory functions of CBD: inhibiting leukocyte migration and limiting inflammatory cytokine production. 11–14

In patients with severe COVID-19, the transition to ARDS is mainly due to the occurrence of cytokine storm and excessive inflammatory responses, including massive production of proinflammatory cytokines such as interleukin (IL)-6 and IL-1β, IL-17, as well as infiltration of neutrophils and monocytes into the lung tissue. 3–5 Currently, other than supportive measures, there is no definitive cure for ARDS, 6,7 illustrating the urgent need for creative and effective therapeutic modalities to treat this complex condition.

CBD improves lung structure and function after intranasal Poly(I:C) treatment. (A) Blood oxygen saturation was reduced (≥10%) by intranasal administration of Poly(I:C). CBD was able to reverse the effect and return the rate of blood oxygen saturation toward the normal level. (B–D) Histological analysis (H, E) of normal lung tissue (B) demonstrated the destruction of normal morphology and structure of lung, hypertrophy, fibrosis, and pulmonary edema, as compared with Poly(I:C)-treated mice (C). CBD treatment (D) improved the structure toward the normal architecture. (E, G) Immunohistochemical analysis of lung tissue showed an increase in the expression level of IL-6 in Poly(I:C)-treated lung compared with normal tissue (E, F). CBD treatment (G) reduced the IL-6 expression in Poly(I:C)-treated lung, indicating the potential protective effect of CBD. (H–J) Immunohistochemical staining for neutrophils (Gr1+LY6G+) showed Poly(I:C) treatment of lung increased neutrophil mobilization compared with the untreated normal lung tissue. CBD treatment curtailed the neutrophil infiltration, suggesting a counter inflammatory role for CBD to limit the ARDS progression. ARDS, acute respiratory distress syndrome; CBD, cannabidiol.

Flow cytometry analysis of lung demonstrated an increase in the frequencies of infiltrating neutrophils (p<0.01), macrophages, and significant elevation (p<0.01) in the expression of proinflammatory cytokines (e.g., IL-6, TNFα, and IFNγ) ( Fig. 2C, D ). CBD treatment reversed all these inflammatory indices and partially re-established homeostasis. In the blood, CBD treatment enhanced the lymphocyte frequencies markedly (p<0.01) while reducing the number of neutrophils and monocytes as well as the level of proinflammatory cytokines significantly (e.g., IL-6, IFNγ, and TNFα) ( Fig. 2E, F ). In the lung, CBD treatment downregulated the number of infiltrating neutrophils and macrophages markedly, and reduced the level of cytokines significantly (p<0.05) ( Fig. 2G, H ).

Results

In brief, all cells were stained with anti-Gr1 (neutrophils), anti-F4/80 (macrophages), and anti-CD3/CD4/CD8 (lymphocytes, all from Biolegend USA). Then cells were fixed and permeabilized and stained intracellularly for cytokines including IL-6, tumor necrosis factor alpha (TNFα), IL-2, and interferon gamma (IFNγ) (proinflammatory cytokines). All samples were run through a 4-Laser LSR II flow cytometer. Cells were gated based on forward and side scatter properties and on marker combinations to select cells of interest. All acquired flow cytometry data were analyzed using FlowJo V10.

Conclusion: Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.

Considering all potential regulatory effects of CBD as well as the vast distribution of endocannabinoid system in the body, it is plausible that CBD may be used as a therapeutic candidate in the treatment of various inflammatory conditions including COVID-19 and other virus-induced ARDS.

Babak Baban

3 Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.

Graphs and summary statistics were also used to assess the results. All statistical tests were two sided. Except for where noted, all p-values presented are unadjusted for multiple comparisons.