Clinical TrialMajor Depressive Disorder (MDD)DMTDMTPlaceboPlaceboRecruiting

Antidepressant Response of DMT Masked With Propofol (DMT4D)

This randomised, placebo-controlled, quadruple-masked trial (n=112) will investigate whether the antidepressant effects of DMT (2 mg/min over 20 minutes; total ~40 mg) in patients with MDD depend on the subjective psychedelic experience by comparing DMT vs placebo under propofol sedation or no sedation.

Target Enrollment
112 participants
Study Type
Phase NA interventional
Design
Randomized, quadruple Blind

Detailed Description

This 2x2 factorial randomized trial compares DMT infusion to placebo, each administered with or without propofol sedation, to determine whether antidepressant effects require the subjective psychedelic experience.

Outcomes include depressive symptom change (MADRS), measures of neuroplasticity and inflammation, safety and adverse events; participants receive a single 20-minute infusion (2 mg/min) with follow-up assessments.

Study Protocol

Preparation

sessions

Dosing

1 sessions
20 min each

Integration

sessions

Study Arms & Interventions

DMT no sedation

experimental

DMT infusion without propofol sedation

Interventions

  • DMT40 mg
    via IV• single dose• 1 doses total

    2 mg/min infusion over 20 min (total 40 mg)

  • Compound
    via Other• single dose

    no sedation

DMT + propofol

experimental

DMT infusion with propofol sedation

Interventions

  • DMT40 mg
    via IV• single dose• 1 doses total

    2 mg/min infusion over 20 min (total 40 mg)

  • Compound
    via IV• single dose

    Propofol sedation ~30 min

Placebo no sedation

inactive

Placebo infusion without propofol

Interventions

  • Placebo
    via IV• single dose• 1 doses total

    Placebo perfusion over 20 min

  • Compound
    via Other• single dose

    no sedation

Placebo + propofol

inactive

Placebo infusion with propofol sedation

Interventions

  • Placebo
    via IV• single dose• 1 doses total

    Placebo perfusion over 20 min

  • Compound
    via IV• single dose

    Propofol sedation ~30 min

Participants

Ages
21 – 99
Sexes
Male & Female

Inclusion 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

  • 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.

Study Details

Locations

University Hospital Basel — Basel, Switzerland

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