Inhaled DMT for major depressive disorder

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2b trial is a multicenter, randomized, double-blind study that compares two inhaled DMT regimens in adults with MDD. Participants are assigned to either a higher-dose DMT sequence (15 mg then 60 mg an hour later) or a lower-dose active comparator (1 mg then 4 mg an hour later). Those not in remission by Day 7 may enter an open-label extension with a higher-dose session on Day 14, with all participants followed up to 12 months to assess durability, safety, functioning, and quality of life. The study aims to determine if rapid-acting inhaled DMT can produce meaningful antidepressant and antisuicidal effects with an acceptable safety profile. Eligibility requires adults 18+ with DSM-5–confirmed MDD, moderate to severe current depression, MADRS ≥ 20, and no recent antidepressant changes or psychedelic use.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 18 years or older, capable of making decisions, and able to provide informed consent.
* Major Depressive Disorder (MDD) according to DSM-5 criteria
* Current depressive episode of moderate to severe intensity
* Episode duration of at least two weeks
* Baseline MADRS score ≥ 20
* No treatment changes (including antidepressants) in the 4 weeks prior to the study
* Abstain from psychedelics ≥14 days before dosing (D0)

Exclusion criteria:

* Major cardiac, hepatic, or renal disease; unstable cardiovascular conditions
* Uncontrolled hypertension, QTc prolongation, arrhythmias, or valvular disease COPD or asthma
* Severe obesity, uncontrolled diabetes, coagulopathy, thyroid disease, or glaucoma
* Neurological risk (e.g., aneurysm, ↑ICP, epilepsy/seizures, severe disorders)
* MAO deficiency or history of serotonin syndrome
* Pregnant, breastfeeding, positive test, or no effective contraception
* Secondary depression
* Cluster B personality disorders (incl. borderline with ≥2 suicidal behaviors in past 12 months) or poor therapeutic rapport
* Psychotic disorders, MDD with psychotic features, or first-degree family history of psychosis/bipolar disorder
* Mania/hypomania
* OCD, dissociative disorders, active PTSD, or decompensated eating disorders
* Moderate-severe use disorder (past 6 months; except nicotine/caffeine)
* Lifetime ketamine, PCP, psychedelics, or MDMA use disorder
* Current use of MAO inhibitors, unless discontinued at least 14 days prior to dosing
* Psychedelic trial participation in past 12 months
* Cognitive impairment affecting valid assessment

Where it's running

• Hospital Universitário Onofre Lopes - HUOL - UFRN
  Natal, Rio Grande do Norte, Brazil Recruiting
• Hospital de Saúde Mental Professor Frota Pinto
  Fortaleza, Ceará, Brazil Not yet recruiting
• Complexo Hospitalar Universitário Professor Edgard Santos, Federal University of Bahia (HUPES-UFBA)
  Salvador, Estado de Bahia, Brazil Not yet recruiting
• Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro (IPUB-UFRJ)
  Rio de Janeiro, Rio de Janeiro, Brazil Not yet recruiting
• Instituto de Psiquiatria - Hospital das Clínicas - IPq - HC - USP
  São Paulo, São Paulo, Brazil Not yet recruiting

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.