East Montgomery Times

Nitrous oxide, commonly recognized as "laughing gas," is showing renewed promise in treating depression, particularly in patients resistant to traditional therapies. Recent findings by researchers at the Perelman School of Medicine at the University of Pennsylvania, published in Nature Communications, indicate that the anesthetic could rapidly alleviate depressive symptoms by acting on specific brain cells in mice.

Dr. Joseph Cichon, assistant professor of Anesthesiology and Critical Care, commented on the unexpected discovery: “Nitrous oxide is the oldest anesthetic we’ve got—it’s been used worldwide for over 180 years, costs about $20 a tank, and yet we’re still learning what it can do.” He compared the research process to an archaeological expedition: “I felt like Indiana Jones, going back in time to crack the mystery of this ancient drug.”

The study challenged previous assumptions about how nitrous oxide works. Historically known to block NMDA receptors within brain cells, the researchers uncovered its action on layer 5 neurons in the cingulate cortex, an area involved in emotional regulation. “We were trying to unlock the secrets of these layer 5 neurons,” Cichon revealed, noting that this aspect “is turning what we thought we knew upside down.”

Collaborating with the University of Chicago and Washington University in St. Louis, the team examined mice under stress. After exposure to nitrous oxide, the affected neurons revived quickly, showing a unique response beyond the typical calming effect of anesthetics. According to Cichon, “Most anesthetics calm the brain, then the effects of the anesthetic fade away. But this one flips a switch--those cells start firing like crazy, and they keep going even after the gas is gone.”

The research offers optimism for patients unresponsive to standard antidepressants. About a third of individuals with depression derive little benefit from existing medications, which may be slow to take effect. Whereas human trials, overseen by Dr. Peter Nagele from the University of Chicago and Dr. Charles Zorumski from Washington University in St. Louis, demonstrated the fast-acting nature of nitrous oxide in alleviating depressive symptoms among treatment-resistant patients.

However, application challenges exist, as the gas must be professionally administered, and potential side effects include mask-induced claustrophobia and nausea. Cichon remained hopeful about future applications: “If we can figure out how to tweak those potassium channels directly in the brain, scientists might be able to develop new depression drugs inspired by this gas.”

The research benefits from funding by the National Institutes of Health and the Brain & Behavior Research Foundation. It offers insights into nitrous oxide's potential and underscores the broader opportunity in revisiting long-understood medications for new therapeutic applications.

For further information, reach out to Matt Toal at 267-600-4871 or matthew.toal@pennmedicine.upenn.edu.