Actively Recruiting

Phase Not Applicable
Age: 21Years +
All Genders
ID06927076

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

Led by University Hospital, Basel, Switzerland · Updated on 2026-04-02

112

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are investigating whether the antidepressant effects of N,N-dimethyltryptamine (DMT) in people with major depressive disorder (MDD) come from biological changes like brain plasticity and reduced inflammation or from the psychedelic experience itself. This study focuses on adults diagnosed with moderate to severe depression and compares DMT's effects with and without the psychedelic experience by masking it using sedation with propofol. Participants will be randomly assigned to one of four groups: DMT with sedation, DMT without sedation, placebo with sedation, or placebo without sedation. The DMT or placebo is given as a 20-minute infusion, while sedation with propofol lasts 30 minutes when used. This design allows researchers to understand if the psychedelic experience is necessary for antidepressant effects or if biological mechanisms alone are responsible. During the study, participants will be assessed for changes in depressive symptoms using several scales at various times up to 14 days after treatment. Researchers will also monitor anxiety, quality of life, psychedelic effects, safety events, and biological markers like neuroplasticity and inflammation. The study includes baseline and follow-up evaluations, mood and personality assessments, and sedation level monitoring, offering a thorough picture of DMT's impact on depression over time.

CONDITIONS

Brief Title

Antidepressant Response of DMT Masked With Propofol

Who Can Participate

Age: 21Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Must meet DSM-5 criteria for moderate or severe major depressive disorder with a MADRS score of 20 or higher
  • Either not currently using antidepressants or on a stable antidepressant dose for at least 4 weeks before randomization
  • 21 years of age or older
  • Sufficient understanding of the German language
  • Able to understand study procedures and risks and willing to follow the study protocol and sign consent
  • Willing not to drive or operate heavy machinery on the day of treatment
  • Willing to limit alcohol, cigarette, coffee, and illicit substance use during participation
  • Willing to use effective contraception throughout the study
Not Eligible

You will not qualify if you...

  • Past or current bipolar or psychotic disorder, including depressive disorder with psychotic features
  • First-degree relative with psychotic or bipolar disorder
  • Significant prodromal psychotic symptoms with a score of 6 or higher on the Prodromal Questionnaire-16
  • Psychiatric conditions incompatible with safe DMT exposure, such as borderline personality disorder
  • Current post-traumatic stress disorder or acute stress reaction
  • Post-partum depression
  • Pregnant or breastfeeding women
  • Significant suicidal ideation or behavior within the past 6 months
  • Severe substance use disorder other than nicotine
  • Planned or recent ketamine, psychedelic, or electroconvulsive treatments within the past 3 months
  • Lifetime use of DMT or more than 15 lifetime uses of other psychedelics or use of other psychedelics within the last 3 months
  • Use of neuroleptics, 5-HT2 antagonists, or MAO inhibitors that cannot be paused
  • Increased risk of adverse reactions to propofol or soy products
  • Increased risk for aspiration or difficult mask ventilation during sedation procedures

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Single day

Participants receive a 20-minute infusion of DMT or placebo, either with 30 minutes of propofol sedation or without sedation, to investigate antidepressant effects.

1 treatment visit (in-person)

Follow-up

Duration - 14 days post-treatment

Participants complete follow-up assessments to monitor changes in depressive symptoms, anxiety, quality of life, safety, and other outcomes over 14 days after treatment.

Visits on day 1, 3, 7, and 14 post-treatment (in-person or remote)

Trial Site Locations

Total: 1 location

1

University Hospital Basel

Basel, Switzerland, 4031

Actively Recruiting

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Research Team

J

Joyce Santos de Jesus

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

4

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