Antidepressant Response of DMT Masked With Propofol

NCT ID: NCT06927076

Last Updated: 2025-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-05

Study Completion Date

2029-03-31

Brief Summary

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The aim of this study is to elucidate if the anti-depressive effect of N,N-dimethyltryptamine (DMT) is based on a biological mechanisms including neuroplasticity and anti-inflammatory effect or due to the subjective psychedelic experience.

Detailed Description

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Major depressive disorder (MDD) affects nearly 20% of people, but current treatments-both pharmacological and psychotherapeutic-have limited efficacy, especially for mild to severe cases. Psychedelics like LSD, psilocybin, and DMT are being explored as alternative therapies, with studies showing promising antidepressant effects. However, it is unclear whether these benefits stem from their acute subjective (psychedelic) experience or from biological mechanisms like neuroplasticity and anti-inflammatory effects.

This study aims to determine if the antidepressant effects of DMT occur independently of its psychedelic experience. To test this, DMT will be administered under sedation (with propofol) to mask subjective effects, as well as without sedation.

Conditions

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Major Depressive Disorder Psychedelic Experiences

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study uses a randomized, double-blind (DMT vs placebo), placebo-controlled, 2x2 factorial parallel group design. Participants are randomly assigned to DMT or placebo (double-blinded) under either sedation with propofol or no sedation (sinlge-blinded).
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
DMT and placebo will be administered in a double-blind fashion. However, investigators immediately involved in the treatment of the specific patient will be informed whether the assignment involves propofol or not. Participants will not be informed about the propofol assignment (single-blind).

Study Groups

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DMT without sedation

DMT without sedation (propofol)

Group Type EXPERIMENTAL

N,N-Dimethyltryptamine

Intervention Type DRUG

administration of a 2mg/min DMT perfusion over 20 min

no sedation

Intervention Type PROCEDURE

no sedation

DMT with sedation

DMT with sedation (propofol)

Group Type EXPERIMENTAL

N,N-Dimethyltryptamine

Intervention Type DRUG

administration of a 2mg/min DMT perfusion over 20 min

Propofol

Intervention Type PROCEDURE

30 min propofol sedation

Placebo without sedation

Placebo (double-blind) without sedation (propofol)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

administration of a placebo perfusion over 20 min

no sedation

Intervention Type PROCEDURE

no sedation

Placebo with sedation

Placebo (double-blind) with sedation (propofol)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

administration of a placebo perfusion over 20 min

Propofol

Intervention Type PROCEDURE

30 min propofol sedation

Interventions

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N,N-Dimethyltryptamine

administration of a 2mg/min DMT perfusion over 20 min

Intervention Type DRUG

Placebo

administration of a placebo perfusion over 20 min

Intervention Type DRUG

Propofol

30 min propofol sedation

Intervention Type PROCEDURE

no sedation

no sedation

Intervention Type PROCEDURE

Other Intervention Names

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DMT

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthias Liechti, Prof. Dr. med.

Role: STUDY_DIRECTOR

University Hospital, Basel, Switzerland

Felix Müller, PD Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

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University Hospital Basel

Basel, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Joyce Santos de Jesus

Role: CONTACT

+41 61 556 65 02

Facility Contacts

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Felix Mueller, PD Dr. med.

Role: primary

+41 61 325 53 94

Other Identifiers

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2024-02312;am24Liechti6

Identifier Type: -

Identifier Source: org_study_id

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