NCT07262008

Sustained Mood Improvement With Laughing Gas Exposure

Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Double-Blind Trial

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Women's College Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Multi-centre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of nitrous oxide on reducing symptoms of depression in patients with treatment resistant depression.

Detailed description

SMILE is a multi-centre, parallel-group, blinded randomized controlled trial of 120 patients with treatment resistant depression. Consented eligible patients will be randomized to 1) Inhalation of Nitrous Oxide + Intravenous Saline (intervention Group)or 2) Inhalation of Oxygen + Intravenous Midazolam (Active Control Group). Participants will receive their respective study intervention once a week for four weeks for a total of four sessions. Follow-up visits will be conducted over the phone 2-weeks, 4-weeks, and 12-weeks following the last intervention visit. Questionnaires will be administered to assess change in depressive symptoms, function, and quality of life.

Conditions

• Major Depressive Disorder
• Treatment Resistant Depression

Interventions

Type	Name	Description
DRUG	Inhalation of Nitrous oxide (Laughing gas) + intravenous saline	Nitrous oxide at an inspiratory concentration of 50% with concurrent intravenous saline (20ml) for one hour.
DRUG	inhalation of %100 oxygen + intravenous midazolam	Inspiration of 100% oxygen with concurrent intravenous midazolam (0.02mg/kg, up to 2 mg) for one hour.

Timeline

• Start date: 2026-02-01
• Primary completion: 2027-02-01
• Completion: 2028-09-01
• First posted: 2025-12-03
• Last updated: 2025-12-10

Locations

5 sites across 1 country: Canada