Antidepressant Response of DMT Masked With Propofol

NCT06927076 | Recruiting DMC

• 1 other identifier: 2024-02312;am24Liechti6
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Psychedelic Experiences; Major Depressive Disorder

Keywords

N,N-dimethyltryptamine (DMT); neuroplasticity

Outcome Measures

Primary Outcomes (1)

• long term changes in depressive symptoms (MADRS)

  Changes in depressive symptoms will be assessed using Montgomery-Asberg-Depression Rating Scale (MADRS). The MADRS is a ten-item questionnaire widely used to measure severity of depressive symptoms during the last week. Total score (range 0-60); higher scores indicate greater depression severity.

  baseline (before intervention) and on day 14 post-intervention

Secondary Outcomes (22)

• Short term changes in depressive symptoms (MADRS)

  Baseline (before intervention) and on day 1, 3 and 7 post-intervention

• Changes in depressive symptoms (BDI)

  Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention

• Changes in anxiety (STAI)

  Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention

• Changes of clinical global impression (CGI-S)

  Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention

• Changes of clinical global impression (CGI-I)

  Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention

Study Arms (4)

DMT without sedation

EXPERIMENTAL

DMT without sedation (propofol)

Drug: N,N-Dimethyltryptamine; Procedure: no sedation

DMT with sedation

EXPERIMENTAL

DMT with sedation (propofol)

Drug: N,N-Dimethyltryptamine; Procedure: Propofol

Placebo without sedation

PLACEBO COMPARATOR

Placebo (double-blind) without sedation (propofol)

Drug: Placebo; Procedure: no sedation

Placebo with sedation

PLACEBO COMPARATOR

Placebo (double-blind) with sedation (propofol)

Drug: Placebo; Procedure: Propofol

Interventions

N,N-Dimethyltryptamine DRUG

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

Also known as: DMT

DMT with sedation; DMT without sedation

Placebo DRUG

administration of a placebo perfusion over 20 min

Placebo with sedation; Placebo without sedation

Propofol PROCEDURE

30 min propofol sedation

DMT with sedation; Placebo with sedation

no sedation PROCEDURE

no sedation

DMT without sedation; Placebo without sedation

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet DSM-5 criteria for MDD of at least moderate severity (MADRS≥20).
• Participants either currently do not use antidepressants or are treated with a stable dose for at least 4 weeks prior to randomization.
• Age ≥ 21 years old.
• Sufficient understanding of the German language.
• Able to understand the study procedures and risks and willing to adhere to the protocol and sign the consent form.
• Willing not to drive or operate heavy machinery on the treatment day.
• 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.
• Willing to use effective contraceptive measures throughout study participation.

You may not qualify if:

• Past or present bipolar or psychotic disorder, including depressive disorder with psychotic features.
• First-degree relative with a psychotic or bipolar disorder.
• Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6).
• 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.
• Current post-traumatic stress disorder or acute stress reaction due to a traumatic event.
• Post-partum depression.
• Pregnant or breastfeeding women.
• Current or recent history of significant suicide ideation or suicide behavior within the past 6 months.
• Current severe substance use disorder other than nicotine.
• Planned ketamine, other psychedelic, or electroconvulsive treatment or any such treatment within the past 3 months.
• 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.
• 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.
• Increased risk for adverse reactions to propofol or soja products.
• Increased risk for aspiration.
• Increased risk for difficult mask ventilation.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

N,N-Dimethyltryptamine; Propofol

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Matthias Liechti, Prof. Dr. med.

  University Hospital, Basel, Switzerland

  STUDY DIRECTOR

• Felix Müller, PD Dr. med.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joyce Santos de Jesus

CONTACT

+41 61 556 65 02; DMT4D@usb.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 4, 2025
• First Posted: April 15, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

CH (1)