Using nitrous oxide to treat major depressive disorder

Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder

Phase 2 Interventional University of Chicago · NCT05357040

This study is testing if nitrous oxide can help adults with major depression who haven't found relief from other treatments feel better.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment172 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity of Chicago Academic / other
Locations2 sites (Chicago, Illinois and 1 other locations)
Trial IDNCT05357040 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the antidepressant effects of nitrous oxide in adults with Major Depressive Disorder (MDD), particularly those who have not responded to traditional treatments. Participants will be randomly assigned to receive either nitrous oxide or a placebo during weekly 1-hour inhalation sessions over four weeks. The study aims to identify the optimal dose and regimen of nitrous oxide to enhance its efficacy and guide future larger trials. The research builds on previous findings that suggest nitrous oxide may provide rapid relief from depressive symptoms.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older diagnosed with Major Depressive Disorder without psychosis.

Not a fit: Patients with a history of bipolar disorder, schizophrenia, or active suicidal intentions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a rapid and effective option for patients suffering from major depressive disorder, especially those resistant to conventional therapies.

How similar studies have performed: Previous studies have shown promising results with nitrous oxide for depression, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Adult (≥18 years, both sexes)
2. DSM-5 criteria for MDD without psychosis, as determined using a structured clinical interview \[Mini International Neuropsychiatric Interview\], MDD, defined by a pre-treatment score \>16 on the HDRS-21 scale and meeting DSM-5 for MDD

Exclusion Criteria:

1. A current or past history of bipolar disorder, schizophrenia, or schizoaffective disorder.
2. Current obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses
3. Active suicidal intention, as determined by clinical interview assessment tool (Sheehan-STS) and clinical examination
4. Active or recent (\<12 months) substance use disorder; excluding nicotine
5. Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
6. Ongoing treatment with ECT
7. Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
8. Pregnancy or breastfeeding
9. Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency unless treated with folic acid or vitamin B12).

Where this trial is running

Chicago, Illinois and 1 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Major Depressive DisorderTreatment Resistant DepressionDepressionAntidepressantNitrous Oxide
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.