Nitrous Oxide Alters Functional Connectivity in Medial Limbic Structures in Treatment-Resistant Major Depression.
Charles R Conway, Ben Julian A Palanca, Thomas Zeffiro...
https://pubmed.ncbi.nlm.nih.gov/39185528Actively Recruiting
Phase 1
Age: 18Years - 65Years
All Genders
Healthy Volunteers
ID02994433
NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits in Treatment-Resistant Major Depression
Led by Washington University School of Medicine · Updated on 2026-04-29
60
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are investigating treatment-resistant major depression (TRMD), a condition where about 15-20% of patients do not respond to standard depression treatments like medication and psychotherapy. This study evaluates the effects of nitrous oxide, a drug that blocks NMDA glutamate receptors, on brain function in both TRMD patients and healthy volunteers. The goal is to understand how nitrous oxide influences brain networks related to emotion and depression using advanced brain imaging techniques. Participants will undergo two inhalation sessions spaced at least one month apart, receiving either one hour of nitrous oxide mixed with oxygen or a placebo gas (nitrogen and oxygen). Up to six functional connectivity MRI scans will be performed to compare brain activity before and after each inhalation session. This allows detailed study of the brain's default mode, affective, and cognitive control networks, among others. During the study, participants will be screened for safety and eligibility, including assessments for MRI compatibility and psychiatric status. Researchers will measure changes in functional brain connectivity two hours after inhalation sessions. The study involves careful monitoring of brain scans, medical history, and clinical evaluations to ensure safety and gather data on nitrous oxide's impact. Participation lasts through two inhalation sessions and multiple MRI scans, with intervals designed to prevent overlap of treatment effects.
CONDITIONS
Brief Title
NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits
Who Can Participate
Age: 18Years - 65Years
All Genders
Healthy Volunteers
Eligibility Criteria
You may qualify if you...
- Adults 18-65 years of age
- Right-handed
- Controls: No major depressive disorder (score ≤7 on Hamilton Depression Rating Scale)
- TRMD patients: Score ≥17 on Hamilton Depression Rating Scale
- Controls: No history of depression confirmed by history and medical records
- TRMD: Documented failure to respond to at least 3-4 adequate antidepressant treatments, including at least 1 in current episode
- Good command of the English language
You will not qualify if you...
- Any DSM-IV Axis I diagnosis except major depressive disorder for TRMD group
- Known primary neurological or medical disorders such as dementia, stroke, encephalopathy, Parkinson's disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac or pulmonary disease
- Use of any central nervous system active medication
- Diseases affecting drug metabolism or excretion (e.g. liver or renal disease)
- Left-handedness
- Not eligible for MRI (e.g. claustrophobia, implanted metal)
- Controls currently using psychotropic medications or drugs for depression or anxiety
- Substance dependence or abuse within past 12 months
- Ability to become pregnant without effective contraception
- Contraindications to nitrous oxide (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency treated with supplements, pregnancy, breastfeeding)
- Inability to provide informed consent
- Any other factor affecting safety or compliance (e.g. living more than 100 miles from clinic)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - 2 sessions separated by a washout period
Participants will undergo two treatment sessions receiving either nitrous oxide or placebo gas by inhalation, in a randomized crossover design.
2 visits (in-person) for inhalation sessions
Follow-up
Duration - 2 hours after each treatment session
Participants are monitored for effects up to 2 hours after each inhalation session.
2 post-treatment visits (in-person) for assessments
Trial Site Locations
Total: 1 location
1
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
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Research Team
B
Britt Gott, MS
A
Anvita Vishwanath, BS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
Nitrous Oxide Reduced Suicidal Ideation in Treatment-Resistant Major Depression in Exploratory Analysis.
Victoria C de Leon, Arun Kumar, Peter Nagele...
https://pubmed.ncbi.nlm.nih.gov/37585253