N2O for Acute Suicidality and Depression in the ED

Inclusion Criteria: * Patients 18-65 years of age, acutely suicidal, presenting to the adult emergency department with documented history of non-psychotic major depressive disorder. Exclusion Criteria: * Current psychotic or catatonic symptoms as determined by the hospital care team. * Unable or unwilling to give consent for study participation (ability to provide consent will be established by treating physician) * Lifetime DSM-V (medical history) diagnoses of schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, and panic disorders. * Meets current DSM-V substance use disorder of greater than mild severity (other than nicotine or marijuana) * Significant pulmonary disease and/or requiring supplemental oxygen. * Administration of other NMDA-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study. * Contraindications for N2O (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure) * Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12. * Women who are pregnant or breastfeeding * Any other factor that in the investigators' judgment may affect patient safety or compliance.