When in an acute respiratory situation, marijuana is not typically something people would think about to relieve their breathing problems. Yet, new data from investigators at the University of South Carolina (UofSC) suggests that the cannabis compound Δ9-tetrahydrocannabinol or THC may prevent acute respiratory distress syndrome (ARDS) when caused by Staphylococcal enterotoxin. ARDS has been mentioned a lot in recent months, as it has been associated with many COVID-19 cases. Findings from the new study—published recently in the British Journal of Pharmacology through an article titled “Protective Effects of Δ9‐Tetrahydrocannabinol Against Enterotoxin‐induced Acute Respiratory Distress Syndrome is Mediated by Modulation of Microbiota”—also suggest a possible treatment for ARDS caused by COVID-19.
“Staphylococcal enterotoxin‐B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing cytokine storm,” the authors wrote. “When SEB is inhaled, it can cause ARDS, which is often fatal and currently there are no effective treatment modalities.”
“Acute respiratory distress syndrome is triggered by a variety of etiologic agents. Currently, there are no FDA-approved drugs to treat ARDS because of which the mortality rate is close to 40%,” added senior study investigator Mitzi Nagarkatti, PhD, professor and chair of the department of pathology, microbiology, and immunology and chair of the Center for Cancer Drug Discovery at UofSC. “Our studies suggest that THC is highly effective to treat ARDS and thus, clinical trials are critical to investigate if this works.”
The incidence of ARDS in the United States is 78.9 per 100,000 persons/year and the mortality rate is 38.5%. When inhaled, SEB can cause ARDS by activating immune cells to produce massive amounts of cytokines leading to “cytokine storm,” which can cause the lungs and other organs to fail, often resulting in death. This immune process is like that seen in patients with severe COVID-19 who are admitted to the hospital and develop ARDS accompanied by a cytokine storm, which leads to respiratory and multi-organ failure. These studies, therefore, raise the exciting possibility of using cannabinoids to treat ARDS seen in COVID-19 patients.
Interestingly, these studies also showed that Staphylococcal enterotoxin alters the microbiome in the lungs leading to the emergence of pathogenic microbiota. But THC helps this symptom too, by promoting beneficial bacteria that suppress inflammation thereby preventing the damage to the lungs.
“We used a mouse model of SEB‐mediated ARDS to test the efficacy of THC,” the authors stated. “These mice were monitored for lung inflammation, alterations in gut and lung microbiota, and production of short‐chain fatty acids (SCFA). Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. Fecal microbiota transplantation (FMT) was performed to confirm the role of microbiota in suppressing ARDS.”
The authors went on to state that “while SEB triggered ARDS and 100% mortality in mice, THC protected the mice from fatality effects. Pyrosequencing analysis revealed that THC caused significant and similar alterations in microbiota in the lungs and gut of mice exposed to SEB. THC significantly increased the abundance of beneficial bacterial species, Ruminococcus gnavus, but decreased pathogenic microbiota, Akkermansia muciniphila.”
The Nagarkatti laboratory has performed decades of pioneering studies on cannabinoids. In fact, their studies on the use of another cannabinoid derived from the cannabis plant, cannabidiol (CBD), to treat autoimmune hepatitis have been well-recognized in the field and have led to FDA approval of CBD as an orphan drug to treat this disorder.
“Cytokine storm is a huge clinical issue which leads to multiorgan failure and often death. It is also seen in COVID-19 patients, and there are no effective treatment modalities against this syndrome,” concluded Nagarkatti. “We have been working on cannabinoids for over 20 years and found that cannabinoids such as THC are highly anti-inflammatory. Thus, our studies raise the exciting suggestion to test THC against ARDS seen in COVID-19 patients.”