Cannabidiol, or CBD, can help reduce cytokine storm and excessive lung inflammation that is killing many patients with COVID-19, the researchers say.
While more work is needed, including clinical trials to determine the optimal dose and timing, before CBD becomes part of the treatment for COVID-19, researchers at the Dental College of Georgia and Medical College of Georgia have early evidence. It could help patients who show signs of respiratory distress avoid extreme interventions such as mechanical ventilation, as well as death from acute respiratory distress syndrome.
“ARDS is an important killer in severe cases of some respiratory viral infections, including coronavirus 2 of severe acute respiratory syndrome (SARS-CoV-2) and we are in urgent need of better intervention and treatment strategies, “says Dr. Babak Baban, immunologist and interim associate dean of research at DCG and corresponding author of the study in the journal Cannabis and Cannabinoid Research.
Drs. Jack Yu and Babak Baban. Credit: Phil Jones, Senior Photographer, University of Augusta.
Our laboratory studies indicate that pure CBD can help the lungs recover from the overwhelming inflammation, or cytokine storm, caused by the COVID-19 virus, and restore healthier oxygen levels in the body, says co-author Dr. Jack Yu, medical scientist and chief of pediatric plastic surgery at MCG.
Their CBD findings were enabled by their additional finding of a safe and relatively inexpensive model to duplicate the lung damage caused by ARDS. Work on the virus itself is limited to a handful of laboratories in the nation that can safely handle the highly contagious virus, and its recently reported approach opens more doors to studying SARS-CoV-2, COVID-19, and conditions. similar virus-induced, they say.
Leveraging the unique and large genetic makeup of the new coronavirus, his model produced classic symptoms of ARDS, such as the overwhelming and destructive immune response, then CBD significantly decreased classic indicators of excess, such as inflammation-promoting cytokines, as It improved oxygen levels in the blood and allowed the lungs to recover from structural damage.
A major problem with SARS-CoV-2 is that, instead of simply killing the virus, the exaggerated immune response can quickly deactivate the lungs, transforming them into a place where the virus replicates, rather than a place that causes Oxygen is available to our bodies and removes potentially harmful gases such as carbon dioxide.
Mechanical ventilators can take over these vital functions for a time and allow critically ill people to use less energy to breathe and have more energy to fight infection, while ideally the lungs recover from the assault. However, the evidence suggests that 30-50% of patients who reach the point of mechanical ventilation do not survive.
The cytokines in these now famous “storms” are a class of molecules like interferon and interleukin, secreted by immune cells and other cells like endothelial cells that line blood vessels, which affect cell communication and can promote and deter inflammation. In the case of COVID-19, there is an overproduction of inflammation-promoting molecules like interleukins IL-6 and IL-1β, as well as immune cells like neutrophils and monocytes, the researchers say.
They observed objective measures of lung function in mice, such as proinflammatory cytokine levels, blood oxygen levels before and after treatment, as well as temperature, an indicator of inflammation. Oxygen levels increased, while temperatures and cytokine levels decreased with CBD therapy. Days later, a more detailed analysis of the lungs reinforced the reduction in key indicators of destructive inflammation, which his model, like the virus, led upward, including reduced levels of IL-6 and infiltrating neutrophils.
In fact, both clinical symptoms and physical lung changes resulting from ARDS were reversed with CBD treatment, they say.
Your model was created with the help of a synthetic double-chain analog RNA called POLY (I: C). In humans, our double chain DNA It contains our genetic information, and our single-stranded RNA carries out instructions from our DNA to produce certain proteins. In the coronavirus family, double-stranded RNA carries the genetic material necessary to reproduce viruses and hijacks the cellular machinery of our bodies to do so, says Baban.
“The virus’s natural instinct is to make more of itself,” says Baban. “It interlocks with our DNA to make the cell produce food and everything it needs.” Viruses also tend to have a tissue or tissues they prefer, some can go anywhere, and for SARS-CoV-2, the lungs are at the top of the list, he says.
Our bodies are not used to this double-stranded RNA, so like the virus, POLY (I: C) receives immediate and extreme attention from the Toll-like 3 receptor, a family of receptors that help our bodies recognize to invaders like a virus and activate our first line, innate immune response.
“Toll receivers 3 see this and just go crazy,” says Yu. The fact that coronaviruses are literally large and have the largest known viral RNA genome makes such a strong cytokine and immune response plausible and likely, Baban adds.
Mice received three doses of POLY (I: C) once daily in the nasal passage. CBD was administered by injection into the abdomen, the first dose two hours after the second POLY (I: C) treatment, then every other day for a total of three days in a process that sought to mimic the mice receiving treatment approximately when humans would begin to experience trouble breathing and would likely seek medical attention. Given too soon, CBD could interfere with an adequate immune response against the virus, Yu says.
CBD rapidly improved clinical symptoms, then detailed studies of the lungs showed damage to its structure, such as overgrowth of tissue, scarring, and swelling, which also resolved in whole or in part. Her next steps include doing similar studies on other organs affected by COVID-19, including the intestine, heart and brain, Baban says.
At least one way that CBD is believed to calm the immune response is because it resembles endocannabinoids, a natural cellular signaling system in our bodies that is believed to be involved in a wide variety of functions, from sleep to reproduction, inflammation and immune response. CB1 and CB2, the primary receptors for this system, are found widely throughout the body, including the brain and respiratory system, where we breathe artificial and natural irritants into the air, as well as viruses and bacteria, which can inflame. While understanding how the natural endocannabinoid system works is still a work in progress, one way CBD works to reduce seizures, for example, is believed to be indirectly through the large number of CB1 receptors in the brain, he says. Yu.
CBD is available over the counter and is used to treat problems such as seizures, as well as Parkinson’s, Crohn’s disease, and other conditions where pain and / or inflammation are a major factor. It is derived from hemp and the cannabis plant, which are essentially the same, although hemp has a much lower concentration of “high production” THC. Other researchers have shown that the calming effect of CBD, for example, can block IL-6 in other models of inflammatory disease.
ARDS is a rapid and serious infection of the lungs that causes widespread inflammation, shortness of breath, rapid breathing, and the inability to maintain adequate levels of oxygen in the body and brain. Difficulty breathing or difficulty breathing are some of the first signs of COVID-19. ARDS is a major cause of death in patients who are seriously ill for a variety of reasons, including common sepsis.
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Reference: “Cannabidiol modulates cytokine storm in simulated viral infection-induced acute respiratory distress syndrome using synthetic RNA” by Hesam Khodadadi, Évila Lopes Salles, Abbas Jarrahi, Fairouz Chibane, Vincenzo Costigliola, Jack C. Yu, Kumar Vaibhav, David C. Hess Krishnan M. Dhandapani and Babak Baban, July 8, 2020, Cannabis and Cannabinoid Research.
DOI: 10.1089 / can.2020.0043
Hesam Khodadadi, a doctoral student at The Graduate School in AU, is the first author of the study; Dr. Évila Lopes Salles, a postdoctoral fellow in Baban’s laboratory, is the second author. Co-authors also include Dr. Kumar Vaibhav, toxicologist at the MCG Neurosurgery Department; Dr. Krishnan M. Dhandapani, neuroscientist, Department of Neurosurgery MCG; and Dr. David C. Hess, neurologist and dean of MCG.
The work was supported in part by the National Institutes of Health.
