Clinical trial NCT06927076: Antidepressant Response of DMT Masked With Propofol
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Psychedelic Experiences
Keywords: N,N-dimethyltryptamine (DMT)
neuroplasticity
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2025-04-15
Enrollment: 112
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 open-label sedation with propofol or no sedation. Assignment to propofol or no sedation is open label. Thus, there is no self-selection into the sedation or non-sedation groups. The assignment is known to the patient and investigator before the blinded treatment with DMT or placebo starts.
Primary purpose: TREATMENT

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.

Detailed description: 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.

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. Borderline personality disorder.
5. Current post-traumatic stress disorder.
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 know antagonists of 5-HT2 receptors or monoamine oxidase inhibitors (MAOI) and are not willing to pause.

Primary outcomes:
measure: long term changes in depressive symptoms (MADRS)
timeFrame: baseline (before intervention) and on day 14 post-intervention
Secondary outcomes:
measure: Short term changes in depressive symptoms (MADRS)
timeFrame: Baseline (before intervention) and on day 1, 3 and 7 post-intervention
measure: Changes in depressive symptoms (BDI)
timeFrame: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention
measure: Changes in anxiety (STAI)
timeFrame: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention
measure: Changes of clinical global impression (CGI-S)
timeFrame: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention
measure: Changes of clinical global impression (CGI-I)
timeFrame: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention
measure: Changes in quality of life (WHOQOL-bref)
timeFrame: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention
measure: Persisting positive and negative effects (PEQ)
timeFrame: On day 14 post-intervention
measure: Acute subjective effects (5D-ASC)
timeFrame: On day 0 post-intervention
measure: Subjective Effects Rating (SES)
timeFrame: On day 0 pre- and post-intervention
measure: States of Consciousness Questionnaire (SCQ)
timeFrame: On day 0 post-intervention
measure: Emotional breakthrough inventory (EBI)
timeFrame: On day 0 post-intervention
measure: Acute adverse effects
timeFrame: On day 0 post-intervention
measure: Safety events
timeFrame: From day 0 to day 14 post-intervention
measure: Neuroplasticity
timeFrame: Baseline (before intervention) and on day 14 post-intervention
measure: Inflammation
timeFrame: Baseline (before intervention) and on day 14 post-intervention
measure: DMT plasma concentration
timeFrame: On day 0 shortly before the end of the perfusion
measure: Expectancy (CEQ)
timeFrame: At Baseline before intervention
measure: Expectancy
timeFrame: At Baseline before intervention
measure: Mood
timeFrame: At day 0 directly before administration of the study drug
measure: Personality (NEO-FFI)
timeFrame: At Baseline before intervention
measure: Personality (TAS)
timeFrame: At Baseline before intervention
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias Liechti, Prof. Dr. med.
role: STUDY_DIRECTOR
affiliation: University Hospital, Basel, Switzerland
name: Felix Müller,, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: