The boon and bane of nitrous oxide.
Golo Kronenberg, Georgios Schoretsanitis, Erich Seifritz, Sebastian Olbrich
European Archives of Psychiatry and Clinical Neuroscience September 1, 2025 DOI: 10.1007/s00406-024-01801-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Keywords | Abuse Homocysteine Methylmalonic acid Nitrous oxide Rapid antidepressant effects |
| Key findings | Nitrous oxide shows potential as a rapid-acting antidepressant, but larger trials are needed to confirm its efficacy and optimal use. |
Abstract
Nitrous oxide (N2O) has been known since the end of the eighteenth century. Today, N2O plays a huge role as a greenhouse gas and an ozone-depleting stratospheric molecule. The main sources of anthropogenic N2O emissions are agriculture, fuel combustion, wastewater treatment, and various industrial processes. By contrast, the contribution of medical N2O to the greenhouse effect appears to be small. The recreational and medical uses of N2O gradually diverged over time. N2O has analgesic and anesthetic effects, making it widely used in modern dentistry and surgery. New research has also begun studying N2O's antidepressant actions. N-methyl-D-aspartate (NMDA) antagonism and opioid effects are believed to be the main underlying biochemical mechanisms. At this point, numerous questions remain open and, in particular, the conduct of larger clinical trials will be essential to confirm N2O's use as a rapid-acting antidepressant. The N2O concentration delivered, the duration of a single inhalation, as well as the number of inhalations ultimately required, deserve to be better understood. Finally, the non-medical use of N2O has gained significant attention in recent years. Sudden deaths directly attributed to N2O are primarily due to asphyxia. Heavy, chronic N2O use may result in vitamin B12 deficiency, which, among other things, may cause megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Helpful biochemical tests include homocysteine and methylmalonic acid. The centerpiece of treatment is complete cessation of N2O use together with parenteral administration of vitamin B12.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 5
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression. European Archives of Psychiatry and Clinical Neuroscience August 29, 2024
- All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants. Pharmacological Research October 1, 2025
- Inhalational nitrous oxide as a transdiagnostic approach for the treatment of suicidal ideation and suicidality in psychiatric inpatients: protocol for a double-blind randomised, controlled clinical single-centre trial. BMJ Open July 16, 2025
- Addressing the Global Challenge of Nitrous Oxide Misuse Through a Multidisciplinary Approach: Example of the PROTOSIDE Network Toxics May 31, 2025
- Commentary on Nitrous Oxide: Weighing the Toxic Neuropsychiatric Effects of Abuse Against Potential Therapeutic Benefits for Psychiatric Disorders. Journal of Psychiatric Practice May 1, 2025
Cites 14
- Ketamine: NMDA Receptors and Beyond Journal of Neuroscience November 2, 2016
- Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial Brazilian Journal of Psychiatry February 18, 2021
- Does nitrous oxide addiction exist? An evaluation of the evidence for the presence and prevalence of substance use disorder symptoms in recreational nitrous oxide users Addiction April 1, 2024
- Diagnosis and management of toxicity associated with the recreational use of nitrous oxide Canadian Medical Association Journal August 20, 2023
- Nitrous Oxide-Induced Cerebral Venous Thrombosis: A Case Report, Potential Mechanisms, and Literature Review Cureus July 1, 2023
and 9 more in the library