DMT for depression with psychedelic effects masked by propofol

Investigating the Role of the Psychedelic Experience in the Antidepressant Response in Patients With Major Depression: a Placebo-controlled Factorial Trial With DMT Masked With Propofol (DMT4D-Study)

This will see if DMT helps adults with moderate-to-severe depression even when its psychedelic effects are masked by propofol sedation.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 21 Years and up
• Sex: All
• Sponsor: University Hospital, Basel, Switzerland (Academic / other)
• Locations: 1 site (Basel)
• Trial ID: NCT06927076 on ClinicalTrials.gov

What this trial studies

Participants with moderate-to-severe major depressive disorder will receive DMT under propofol sedation, DMT without sedation, or placebo, with mood assessed over follow-up. The trial will collect biological measures related to neuroplasticity and inflammation alongside standardized depression scales (e.g., MADRS) to link clinical effects with biological changes or subjective experience. Eligible participants are adults (≥21) who can consent, speak German, and are either medication-free or on a stable antidepressant dose; dosing and monitoring occur in a medical setting. All treatment visits are conducted in-person with medical monitoring at the study site.

Who should consider this trial

Good fit: Adults aged 21 or older with moderate-to-severe major depressive disorder (MADRS ≥20) who can consent, speak German, and are either off antidepressants or on a stable dose are potential candidates.

Not a fit: People with current or past bipolar or psychotic disorders, a first-degree relative with those conditions, pregnancy, or other medical contraindications are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, this approach could provide a rapid-acting antidepressant that works without a psychedelic experience, broadening access and reducing the need for intensive therapeutic settings.

How similar studies have performed: Other trials of psychedelics such as psilocybin and DMT have shown rapid antidepressant effects, but masking the subjective psychedelic experience with sedation is a novel and relatively untested approach.

Eligibility criteria

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.

Where this trial is running

Basel

• University Hospital Basel — Basel, Switzerland (Recruiting)

Study contacts

• Principal investigator: Felix Müller, PD Dr. med. — University Hospital, Basel, Switzerland
• Study coordinator: Joyce Santos de Jesus

Conditions Major Depressive Disorder; Psychedelic Experiences; N,N-dimethyltryptamine; neuroplasticity