Nitrous Oxide for Major Depressive Disorder

Recruiting at 1 trial location

Overseen By Anvita Vishwanath, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Psychotropics, Antidepressants

Disqualifiers: Neurological disorders, Severe cardiac disease, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how nitrous oxide, a type of gas, might benefit individuals with treatment-resistant major depression (TRMD) who haven't responded to other treatments. Researchers aim to observe nitrous oxide's effects on the brain using advanced imaging techniques. Participants will inhale either nitrous oxide or a placebo gas, allowing comparison of brain images before and after the sessions. Individuals whose depression hasn't improved with at least three different treatments might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative treatment.

Is there any evidence suggesting that nitrous oxide is likely to be safe for humans?

Research has shown that nitrous oxide is generally safe when used correctly. Medical settings, such as dental procedures, have safely used it for many years. However, some side effects may occur, including dizziness or drowsiness. These effects are usually temporary and subside once inhalation stops.

Safety guidelines stress careful use of nitrous oxide. It can displace oxygen in the air, potentially leading to suffocation if misused. Therefore, using nitrous oxide in well-ventilated areas and under professional supervision is crucial.

In summary, while nitrous oxide is mostly considered safe, following safety guidelines is essential to reduce risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nitrous oxide is unique because it targets NMDA receptors in the brain, which are involved in mood regulation. Unlike traditional antidepressants that often take weeks to show effects, nitrous oxide might provide rapid relief from depressive symptoms. Researchers are excited about this treatment because it offers a new mechanism of action compared to standard antidepressants, potentially benefiting patients who don't respond well to existing medications. Additionally, the one-hour inhalation method is a novel delivery system that could offer convenience and quicker onset compared to oral medications.

What evidence suggests that nitrous oxide might be an effective treatment for treatment-resistant major depression?

This trial will compare the effects of nitrous oxide with a placebo gas. Studies have shown that nitrous oxide can quickly relieve symptoms in people with treatment-resistant major depression (TRMD). In a recent study, just one session with nitrous oxide gas quickly reduced depression symptoms. The treatment proved effective at both low (25%) and moderate (50%) concentrations during one-hour sessions. Patients noticed significant improvements, suggesting nitrous oxide might be a promising new option for TRMD. Research shows that these positive effects are consistent and repeatable, making nitrous oxide a strong candidate for further studies in depression treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Charles R Conway, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

Adults 18-65 years of age

Right-handed

Controls must not meet the DSM-IV criteria for major depressive disorder (MDD) by scoring ≤7 on the HDRS; Treatment-Resistant Major Depression (TRMD) patients must meet a ≥17 score on the HDRS

Exclusion Criteria

Meets criteria for any DSM-IV Axis I diagnosis 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Inhalation Sessions

Participants undergo two inhalation sessions with nitrous oxide and placebo gas, separated by at least one month

2 months

2 visits (in-person)

Functional MRI Scans

Participants undergo up to six functional connectivity MRI scans to trace brain interconnections

2 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nitrous Oxide

How Is the Trial Designed?

Group I: Nitrous Oxide Experimental Treatment 2 Interventions

One hour inhalation of nitrous oxide

Group II: Placebo Gas Placebo Group 2 Interventions

One hour inhalation of placebo gas

Nitrous Oxide is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Nitrous oxide for:

• Anesthesia
• Pain relief
• Hypoxic respiratory failure in neonates

Approved in United States as Nitrous oxide for:

• Anesthesia
• Pain relief
• Hypoxic respiratory failure in neonates

Approved in Canada as Nitrous oxide for:

• Anesthesia
• Pain relief
• Hypoxic respiratory failure in neonates

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8637914/

Success rate of nitrous oxide-oxygen procedural sedation in ...

According to this systematic review and meta-analysis, the estimated efficacy rates of NOIS in global, adult, and pediatric populations were 94.9% (95% CI: 88.8 ...

2.

thelancet.com

thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00467-0/fulltext

Nitrous oxide for the treatment of depression: a systematic ...

N2O demonstrates rapid, reproducible antidepressant effects in early-phase trials. Its future clinical value depends on whether these effects ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8985494/

Current status of nitrous oxide use in pediatric patients - PMC

No major adverse effects have been reported in large trials on the use of nitrous oxide in children despite the prevailing concerns over its safety in this ...

4.

news.uchicago.edu

news.uchicago.edu/story/low-doses-laughing-gas-could-be-effective-treating-severe-depression

Low doses of 'laughing gas' could be effective in treating ...

Louis found that a single inhalation session with 25% nitrous oxide gas could rapidly relieve symptoms of treatment-resistant depression. The ...

5.

cdn.who.int

cdn.who.int/media/docs/default-source/46th-ecdd/nitrous-oxide_46th-ecdd_critical-review_public-version.pdf

Pre-review report: Nitrous oxide

Among 4883 respondents in the 2014 global drug survey (data collected in late 2013) who reported use of nitrous oxide in the past year, 80.6% had inhaled ...

6.

airgas.com

airgas.com/msds/001042.pdf

SAFETY DATA SHEET

Prevention. : P220 - Keep away from clothing and other combustible materials. P244 - Keep reduction valves, valves and fittings free from oil and grease.

7.

static.gasandsupply.com

static.gasandsupply.com/SDS/Nitrous%20Oxide%20SDS.pdf

Safety Data Sheet - Nitrous Oxide

Avoid breathing gas. Use and store only outdoors or in a well ventilated place. Other Hazards: This product may displace oxygen and cause rapid suffocation,.

8.

osha.gov

osha.gov/chemicaldata/4

NITROUS OXIDE | Occupational Safety and Health ...

Nitrous oxide: Chemical Identification, Physical Properties, Monitoring Methods Used by OSHA. All sampling instructions above are recommended guidelines.

9.

produkte.linde-gas.at

produkte.linde-gas.at/sdb_konform/N2O_10021720EN.pdf

SAFETY DATA SHEET Nitrous oxide SECTION 1

Specific Target Organ Toxicity -. Single Exposure. Category 3. H336: May cause drowsiness or dizziness. 2.2 Label Elements. Contains: Dinitrogen ...

10.

uscylgas.com

uscylgas.com/content/Nitrous%20Oxide%20Safety%20Data%20Sheet.pdf

Safety Data Sheet - Nitrous Oxide

Hazard Statements: H280: Contains gas under pressure; may explode if heated. H270: May cause or intensify fire; oxidizer. OSHA-H01: MAY DISPLACE ...