Famotidine (Pepcid) Activates the Vagus Nerve to Reduce Cytokine Storm in COVID-19, New Study Shows
20 May 2022 - - A phase two clinical trial has shown the efficacy of famotidine, commonly known as Pepcid, in alleviating coronavirus disease 2019 (COVID-19) symptoms in adult patients, the New York-based The Feinstein Institutes for Medical Research said.

In a new study, scientists at The Feinstein Institutes for Medical Research discovered this widely used heartburn medication stimulates the vagus nerve, which suppresses cytokine storm a severe immune reaction where the body releases too many inflammatory proteins into the blood too quickly a hallmark of COVID-19.

The preclinical study published in the journal Molecular Medicine shows that famotidine, a histamine 2 receptor antagonist, prevents cytokine storm in mice.

Surprisingly, famotidine did this indirectly because it stimulated signals caused by the vagus nerve, a major nerve traveling from the brain, through the neck, into the body's organs.

Investigators found that increased vagus nerve signals were why famotidine injections stopped cytokine storms.

By cutting the vagus nerve, known as a "vagotomy," it prevented the ability of famotidine to stop the cytokine storms.

In the early 2000s, Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes, and colleagues discovered how the vagus nerve turns off inflammation in the body, a process now called the inflammatory reflex.

If the inflammatory reflex or vagus nerve is impaired, the result is an unchecked abundance of inflammation, which can contribute to autoimmune diseases, including rheumatoid arthritis and Crohn's disease.

By understanding this feedback loop between the brain and body, Dr. Tracey helped pioneer the field of bioelectronic medicine and neuromodulation, using devices to electrically stimulate the vagus nerve as a therapy to prevent inflammation.

The new evidence reveals a critical vagus nerve role in preventing COVID-19's dangerous cytokine storms.

When famotidine was administered to mice, it significantly reduced serum and spleen levels of the cytokines TNF and Interleukin 6 and improved survival, which means that the inflammatory reflex is famotidine's mechanism of action.

Researchers noted that future studies are needed to replicate the findings of using famotidine to combat COVID-19 and that this new research was conducted in animal models, not humans.

Just as direct electrical stimulation of the vagus nerve has shown to improve a variety of diseases, famotidine too a well-tolerated and generic drug may one day offer additional methods of activating the inflammatory reflex to reduce inflammation.

At the start of the COVID-19 pandemic, the Feinstein Institutes began to study the safety and efficacy of famotidine in clinical trials.

Most recently, findings from a fully-remote, randomized, double-blind, placebo-controlled clinical trial led by Northwell Health and Cold Spring Harbor Laboratory were published in the journal Gut.

The trial results confirm that famotidine leads to earlier resolution of inflammation in patients and alleviates symptoms of the disease, including improvement in breathing, chest congestion, cough and the return of taste and smell.

The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State.

Encompassing 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health system science, and molecular medicine.