Sustained Mood Improvement With Laughing Gas Exposure
Key facts
- Where
- Toronto, CanadaSee the 5 sites
- Phase
- Phase 3
Could this be for you?
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- Are you between 18 and 65 years old?
Source: NCT07262008, who can take part
Where in Canada
- St. Michael's Hospital (Unity Health)Toronto, CanadaNo longer taking part
- Sunnybrook Health Sciences CentreToronto, CanadaNo longer taking part
- Toronto General Hospital, UHNToronto, CanadaNo longer taking part
- Toronto Western Hospital (UHN)Toronto, CanadaNo longer taking part
- Women's College HospitalToronto, CanadaNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Women's College Hospital
- Trial code
- NCT07262008
- Record updated
- 10 December 2025
- Original description
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.Read full original descriptionShow less
Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Double-Blind Trial
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.
Inclusion: 18 to 65 years of age; Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD); Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5; Experiencing moderate to severe depressive episodes, as defined by the Montgomery-Åsberg Depression Rating Scale (MADRS) > 21; Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode; For women of childbearing potential, use of highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the female participant; Capacity to provide informed consent.
Exclusion: Contraindication to receiving nitrous oxide (e.g. any condition where air is entrapped within a body and its expansion might be dangerous such as, pneumothorax, elevated intracranial pressure, air embolism, recent middle ear, vitreoretinal or bowel obstruction surgeries, etc.); Contraindication to receiving the placebo midazolam (e.g. shock, chronic heart failure, chronic obstructive pulmonary disease, closed-angle glaucoma, renal failure, patients with limited pulmonary reserve or those with severe decline of vital signs); Received electroconvulsive therapy within the past six months; Received ketamine treatment within the past six months; Received repetitive transcranial magnetic stimulation within the past six months; Diagnosis of Bipolar Disorder; Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year; Dementia; Current or lifetime history of schizophrenia or schizoaffective disorder; Known history of hypersensitivity or allergy to nitrous oxide, midazolam or any ingredients in the study formulations; Known chronic cobalamin or folate deficiency (e.g. signs of anemia or neurological symptoms, with plasma levels of homocysteine over 15 µmol/L and abnormal red blood cells and leukocytes on a complete blood count CBC) or current methotrexate use; Acute suicidality defined as score > 4 on MADRS item 10; Daily use of centrally acting medicinal products, such as opioid agonists, (e.g. naloxone and naltrexone) morphine derivatives (e.g. oxycodone, hydrocodone, oxymorphone, codeine), benzodiazepines (e.g. diazepam, clonazepam, alprazolam) and/or other central nervous system depressants such as barbiturates (e.g. phenobarbital, pentobarbital, amobarbital) and alcohol within the past week; Pregnancy or breastfeeding; Unwilling to maintain current antidepressant regimen.