Antidepressant Response of DMT Masked With Propofol

Inclusion Criteria: 1. Participants must meet DSM-5 criteria for MDD of at least moderate severity (MADRS≥20). 2. Participants either currently do not use antidepressants or are treated with a stable dose for at least 4 weeks prior to randomization. 3. Age ≥ 21 years old. 4. Sufficient understanding of the German language. 5. Able to understand the study procedures and risks and willing to adhere to the protocol and sign the consent form. 6. Willing not to drive or operate heavy machinery on the treatment day. 7. Willing to refrain from more than 7 standard alcoholic drinks a week, more than 10 cigarettes a day, more than 2 cups of coffee a day, and any illicit substances during study participation. 8. Willing to use effective contraceptive measures throughout study participation. Exclusion Criteria: 1. Past or present bipolar or psychotic disorder, including depressive disorder with psychotic features. 2. First-degree relative with a psychotic or bipolar disorder. 3. Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6). 4. Psychiatric condition judged to be incompatible with establishment of rapport with study team members and/or safe exposure to DMT, e.g. diagnosed or suspected borderline personality disorder. 5. Current post-traumatic stress disorder or acute stress reaction due to a traumatic event. 6. Post-partum depression. 7. Pregnant or breastfeeding women. 8. Current or recent history of significant suicide ideation or suicide behavior within the past 6 months. 9. Current severe substance use disorder other than nicotine. 10. Planned ketamine, other psychedelic, or electroconvulsive treatment or any such treatment within the past 3 months. 11. Any lifetime use of DMT, use of any other psychedelics within last 3 month or lifetime use of any other psychedelics more than 15 times. 12. Patients who are treated with neuroleptics or known antagonists of 5-HT2 receptors or monoamine oxidase inhibitors (MAOI) and are not able/willing to pause. 13. Increased risk for adverse reactions to propofol or soja products. 14. Increased risk for aspiration. 15. Increased risk for difficult mask ventilation.