A Smart Pill to Reduce Stress

The gut plays a major role in stress levels in the human body. Often called the “second brain,” the gut constantly talks to the brain, influencing mood, and regulating stress hormones like cortisol. Doctors know that persistently high levels of cortisol negatively affect the human body. What they haven’t figured out is a precise way to control it, until now.

Researchers from Carnegie Mellon University aim to develop a swallowable smart pill that temporarily lives in the gut and reduces stress hormones by precisely stimulating gut nerves, all without surgery or drugs. The team recently received funding through the Defense Advanced Research Projects Agency (DARPA) to support its CoasterChase program.

The technology, called GutHarmony, could temporarily change how gut nerves function in order to reduce stress in the body. Once swallowed, the pill dissolves in the lower portion of the small intestine, releasing a tiny, soft stent-like device that remains in place for a few days. Once there, it can sense chemical signals linked to stress and deliver tiny, targeted stimulations to modulate activity in gut nerves and hormone-releasing cells.

“If high levels of cortisol are detected, the device will direct your adrenal glands to ease off production, lowering stress levels in the body,” says Pulkit Grover, the principal investigator on the project, and a professor of electrical and computer engineering, biomedical engineering, and CMU’s Neuroscience Institute. 

The first fully ingestible closed-loop neuromodulation system, GutHarmony would continuously sense chemical levels and would only adjust electrical stimulations when high levels of cortisol are detected. Whereas an open-loop neuromodulation system lacks the detection feature and will continuously release preprogrammed stimulation, no matter the chemical levels.

“Our closed-loop neuromodulation system offers a personalized treatment plan,” explains Zeynep Temel, associate professor in CMU’s Robotics Institute and co-lead on the project. “Current stress treatments affect the entire brain and body, often causing unwanted side effects. GutHarmony offers precision stress control, using electronics instead of chemistry, and doing it from inside the gut.”

The smart pill has three distinctive features; the outer capsule, which dissolves only in the lower intestine, the flexible stent that unfolds, anchors gently, and carries sensors and stimulators, and the electronics module, containing power, control, and communication.

“Our swallowable device can deploy itself inside the gut and keep working for days,” says Grover. “It’s an extremely small, low-power electronic device, built for sensing, stimulation, and precision control. A key aspect is maximizing its effect on stress, while minimizing side effects, which requires an interdisciplinary mindset integrating mechanistic understanding with cutting-edge engineering design.”

The aim of the technology is to significantly reduce cortisol production under stress, improve cognitive and behavioral performance, a reliable deployment and safe exit from the body, all with minimal side effects.

“The technology sounds like sci-fi, but it’s surprisingly elegant,” says Mats Forssell, an electrical and computer engineering research scientist and co-lead on the project. “You swallow a capsule. When it reaches a specific part of the intestine, it dissolves and releases a soft, flexible structure, kind of like a microscopic stent. This structure stays put for several days, during which an electronic circuit works continuously to sense and modulate gut neurons, and then the device breaks apart and exits naturally."

“This technology could change the way stress-related disorders are treated,” says Douglas Weber, the Akhtar and Bhutta Professor of Mechanical Engineering, CMU’s Neuroscience Institute, and co-lead on the project. “It opens up a new kind of medicine that uses ingestible electronics instead of drugs.”

The team sees GutHarmony as more than a single device. It is a proof of concept for a new class of therapies: ingestible machines that sense, decide, and act inside the body, then disappear.

In other words, the future of mental health treatment might not be something you take every day. It might be something you swallow once, and your gut takes it from there.

The effort also includes co-leads Mohammad Islam, professor of material science and engineering, as well as a cross-departmental collaboration including Carnegie Mellon investigators Burak Ozdoganlar, Keith Cook, Maysam Chamanzar, Sarah Bergbreiter, Tzahi Cohen-Karni, Jana Kainerstorfer, Swarun Kumar, Anthony Rowe, and Marc Dandin.