Journal of neurophysiology
May 1, 2025
Petra Valtonen, Stanislav Rozov, Iina Annala et al.
Short-term administration of nitrous oxide (N2O) increases power in the theta frequency range (4-7 Hz) of the electroencephalogram (EEG) after the gas is withdrawn, but does not affect delta frequency (0.5-4 Hz) power. In a study of 14 healthy male participants, those receiving 50% N2O either continuously for 20 minutes or in two 10-minute inhalations showed rapid EEG transitions during gas administration and withdrawal. Power in high-frequency gamma bands increased during N2O, while beta and alpha frequencies decreased. After withdrawal, theta power increased in several electrodes, with negligible differences between the two treatment groups. The effect was reproducible with repeated dosing.
Acta anaesthesiologica Scandinavica
August 1, 2024
Petra Valtonen, Saara Markkanen, Kaija Järventausta et al.
Nitrous oxide, increasingly used for sedation and pain control rather than general anesthesia, produces highly variable subjective experiences that are not always pleasant. In twenty healthy male volunteers who inhaled 50% nitrous oxide for 20 minutes, qualitative analysis of open-ended responses revealed two overarching themes: the drug is mind-altering and causes sensory overload. Mind-altering effects included dreamlike states—encompassing changes in consciousness and scary, bizarre, or transcendental dreams, but no pleasant dreams—and heightened emotions such as euphoria, anxiety, and fear of losing control. Sensory overload comprised distorted perception, bodily sensations, and a heightened sense of surroundings. These findings help clinicians understand patient likes and dislikes during nitrous oxide sedation.
Molecular neurobiology
June 1, 2019
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
The antidepressant effects of NMDA receptor blockers like ketamine and nitrous oxide (laughing gas) become apparent only after their acute psychoactive effects wear off. In mice, nitrous oxide exposure initially increased markers of neuronal excitability, but regulation of the BDNF receptor TrkB and GSK3β signaling occurred gradually after drug discontinuation, during a brain state dominated by slow EEG activity. Subanesthetic ketamine and seizure-inducing flurothyl also produced slow oscillations after their acute effects subsided. A sedative that directly induces slow oscillations did not increase neuronal excitability markers or produce antidepressant-like behavior, suggesting that transient cortical excitability followed by homeostatic slow oscillations and TrkB-GSK3β signaling are critical for rapid antidepressant responses.
Samuel Kohtala, Wiebke Theilmann, Marko Rosenholm et al.
preprint
Nitrous oxide (laughing gas), a dissociative anesthetic that blocks NMDA receptors, produces rapid antidepressant effects in animals through a mechanism that emerges after the drug is withdrawn, not during its peak action. The gas induces rebound slow EEG oscillations, a brain state also seen with ketamine and electroconvulsive therapy, that is characterized by sedation and drowsiness. During this withdrawal phase, signaling changes in TrkB and GSK3β proteins gradually appear, suggesting that the antidepressant effect relies on cortical excitability triggered by the drug's offset rather than its acute presence.