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Nitrous Oxide for Treatment-Resistant Depression

This study is looking at how nitrous oxide, an anesthetic gas, affects the brains of people with major depression that hasn't responded to other treatments (treatment-resistant major depression) and healthy volunteers. Researchers want to understand how nitrous oxide works in the brain by using special brain scans (MRI). You might be eligible if you are between 18 and 65 years old. The study will compare brain activity after receiving either nitrous oxide or a placebo gas. The main goal is to see how these gases change connections in different brain networks related to mood and thinking, measured two hours after inhalation. The study plans to enroll 60 participants.

Study design
This is an interventional study comparing nitrous oxide to a placebo gas. It plans to enroll 60 participants.
What's involved
You would receive either nitrous oxide or a placebo gas. You would also undergo MRI scans to measure brain activity.
Compensation
Not stated in the trial record.
Follow-up
Brain activity will be measured two hours after gas inhalation.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT02994433

NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits

Recruiting
PHASE1Ages 18–65InterventionalTreatment
Washington University School of Medicine
~60 participants
Updated 2026-04-29 on ClinicalTrials.gov
What's tested:Nitrous OxidePlacebo gasMRI

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Comparison of functional connectivity between default mode network of treatment-resistant depressed and non-depressed participants
Measured over 2 hours after inhalation
+3 more outcomes measured

Conditions

Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant

Explore related trials

Unipolar Depression

Where it's being run

1 sites across 1 states
Missouri1

Study leadership

  • Charles R Conway, MD · PRINCIPAL_INVESTIGATOR · Washington University School of Medicine

Who to contact

Britt Gott, MS
[email protected]
314-362-2463
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Adults 18-65 years of age
Right-handed
Controls: Not meet The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD) by scoring ≤7 on the Hamilton Depression Rating Scale (HDRS), 17-item; Treatment-Resistant Major Depression (TRMD) patients: Must meet a ≥17 score on the HDRS.
Controls: Must not have any history of depression as determined by reported history and medical record review; TRMD: Documented (chart review) failure to respond to ≥3-4 adequate dose/duration antidepressant treatments; ≥1 in the current depressive episode.
Good command of the English language

Exclusion

Meets criteria for any DSM-IV Axis I diagnosis as documented in medical records and as determined by structured clinical interview (except MDD for the TRMD group)
Known primary neurological disorders or medical disorders including dementia, stroke, encephalopathy Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac or pulmonary disease
Any central nervous system active medication as determined by study investigator
Any known disease affecting drug metabolism and excretion (e.g. renal or liver disease) as determined by study investigator
Left-handedness
Not eligible for MRI scans (e.g. history of claustrophobia/implanted metal as per MRI Screening Tool)
Current use of psychotropic medications, antidepressants, or prescription or non-prescription drugs/herbals intended to treat depression or anxiety (control group only)
Any recent (within past 12 months) history of substance dependence or abuse, determined by reported history or urine drug screen
Ability to become pregnant and not using effective contraception
Contraindication against the use of nitrous oxide:
Inability to provide informed consent
Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic).

What this trial measures

  • Comparison of functional connectivity between default mode network of treatment-resistant depressed and non-depressed participants2 hours after inhalation

    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.

  • Comparison of functional connectivity between affective network of treatment-resistant depressed and non-depressed participants2 hours after inhalation

    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.

  • Comparison of functional connectivity between cognitive control network of treatment-resistant depressed and non-depressed participants2 hours after inhalation

    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.

  • Comparison of functional connectivity between dorsal nexus of treatment-resistant depressed and non-depressed participants2 hours after inhalation

    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.