Nitrous Oxide for Depression

Nitrous Oxide - Lone Star Infusion

We offer nitrous oxide inhalation treatments.

Similar to ketamine:

Nitrous oxide works on some of the same pathways as ketamine and may be a good option for severe treatment-resistant depression. The nitrous treatment is similar to a ketamine treatment – resting in a comfortable chair to receive the medication for an hour - but uses a soft mask to deliver the gas mixture instead of an IV, and nitrous has less visual and sensation hallucinations than with a ketamine infusion.

We offer nitrous as an alternative to ketamine for patients who can’t stand the IV, or who don’t prefer the experience of ketamine, or who need to drive themselves (after a recovery period, of course).

What it is and how it works:

Nitrous oxide, also called laughing gas, was discovered in 1772. It is a clear gas with a pleasant, sweetish odor and taste. Inhalation of small amounts causes a euphoric affect, and in larger amounts it causes an anesthetic effect. It was quickly adopted, and still used widely, as a safe make option to make dental procedures tolerable. By the 1880s women were using it for pain relief during childbirth - including, famously, Queen Victoria!

Nitrous oxide affects many receptors in the nervous system including, but not limited to: dopamine receptors, alpha-2 adreno-receptors, benzodiazepine receptors, and N-methyl, d-aspartate (NMDA) receptors. NMDA receptor antagonism is also a mechanism of action for ketamine, and is generally theorized to be the most likely mechanism by which ketamine is so effective as treatment for depression – this also explains nitrous oxide’s potent anti-depressant promise.

Efficacy and safety:

There is limited research on the efficacy of nitrous oxide inhalation treatments for depression, however:

Nitrous oxide is very safe when carefully and thoughtfully administered by a trained professional in a monitored setting with a carefully titrated dose and correct dose spacing and supplementation. However, recreational or “street” use can easily lead to hypoxia and death. With very extreme and prolonged exposures, patients can have difficulty metabolizing vitamin B12 which can lead to anemia and nerve damage – these exposures are far greater than from periodic clinical treatments and we do not expect to see these issues.

We strive to help our patients with the best-available evidence based medicine. We are excited to offer these nitrous oxide treatments. If you are interested in pursuing treatments, please contact us.


"Laughing Gas as a Treatment for Depression?" Eugene Rubin, Psychology Today, 2015

“Laughing gas studied as depression treatment” Jim Dryden, the SOURCE, Washington University in St Louis, December 9, 2014

Nagele et al “Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial” Biological Psychiatry July 1,2015

Zarate and Machado-Vieira “Potential Pathways Involved in the Rapid Antidepressant Effects of Nitrous Oxide” Biol Psychiatry. 2015 Jul 1

Kohtala et al “Putative rapid-acting antidepressant nitrous oxide ("laughing gas") evokes rebound emergence of slow EEG oscillations during which TrkB signaling is induced” March 2018

“Laughing Gas to Be Used as Antidepressant in Australian Medical Trial” Gavin Butler, VICE, Apr 17 2019

Nagele, Zorumski, Conway “Exploring Nitrous Oxide as Treatment for Mood Disorders: Basic Concepts” J Clin Psychopharmacol. 2018 Apr


About Me, Dr Allison Wells: I started Lone Star Infusion, here in Houston, to provide ketamine infusions for depression, anxiety, PTSD, CRPS and other mood disorders and pain conditions. I am a licensed, board-certified anesthesiologist. I am super passionate about being a partner in helping people feel their best with evidence-based medicine.

An Important Disclaimer: The information in this and other blog posts represents my informed opinion or the opinion of others, and does not constitute medical advice and should not be relied upon to make decisions regarding medical care. To address the specific details of your medical conditions and treatments please speak with your doctors.

Dr. Allison Wells, MD

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