Could laughing gas help alleviate depression? This seemingly whimsical idea has been rigorously tested by researchers, with encouraging results from low doses of nitrous oxide.
Commonly used as an anesthetic, nitrous oxide (N₂O), or laughing gas, is also recreationally misused by some young people seeking its quick euphoric high from gas cartridges. While this practice carries risks and has surged recently in France, a study published June 9, 2021, in Science Translational Medicine explores a therapeutic potential. Conducted by Washington University School of Medicine in St. Louis, USA, the research demonstrates that low-dose inhalation can rapidly improve depression symptoms.
Nitrous oxide acts primarily by blocking NMDA (N-methyl-D-aspartic) receptors in nerve cells— the same targets as ketamine, a potent anesthetic with proven antidepressant effects. Yet, the exact way these receptors influence mood remains unclear.
Inspired by ketamine's success against depression, lead researcher Peter Nagele hypothesized similar benefits from nitrous oxide. His team’s 2014 study showed that one hour of inhalation reduced symptoms for up to a day in patients unresponsive to standard antidepressants.
Prolonged exposure can trigger nausea and headaches, so the recent trial refined dosing. Researchers tested effects on 24 treatment-resistant patients, administering placebo (air + oxygen), half-dose, or full-dose nitrous oxide monthly for three months. Two weeks post-treatment, the half-dose group saw depression scores drop by an average of five points on the Montgomery-Åsberg Depression Rating Scale compared to placebo.
The full-dose group experienced slightly greater reductions, though differences from half-dose were minimal and possibly due to chance. Crucially, full doses caused more side effects like migraines, nausea, and dizziness. This identifies low doses as ideal for balancing efficacy and tolerability.
