RecruitingPhase 2

Inhaled DMT for Major Depressive Disorder

Brazil140 participantsStarted 2026-08-01

Plain-language summary

This Phase 2b, randomized, double-blind, active-controlled clinical trial will evaluate the efficacy and safety of inhaled N,N-dimethyltryptamine (DMT) in adults with Major Depressive Disorder (MDD). The study will test whether inhaled DMT can rapidly reduce depressive symptoms and suicide risk compared with a low-dose active comparator. A total of 140 participants will be randomized 1:1 to receive either 15 mg followed 1 hour later by 60 mg of inhaled DMT, or 1 mg followed 1 hour later by 4 mg of inhaled DMT. Participants who do not achieve remission at Day 7 will enter an open-label extension and receive a high-dose DMT session on Day 14 (±3 days). All participants will be followed for up to 12 months to evaluate the durability of response, safety, functioning, and quality of life.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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) and during the 12-month follow-up 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 (YMRS ≥8) * 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 …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1This trial is specifically tracking suicidal ideation as a safety outcome using a formal scale — given my current symptoms, does my doctor think it's safe for me to participate in a study that's still in Phase 2 and hasn't yet fully established the safety profile of inhaled DMT?
2Since this is a Phase 2 trial measuring whether inhaled DMT actually reduces depression scores on the MADRS scale, what does my doctor think about how much is currently known versus unknown about whether this treatment works, and would trying a standard antidepressant first make more sense for my situation?
3DMT is a powerful psychedelic that affects perception and consciousness — what does my doctor know about what the experience of inhaling it is actually like, and what kind of monitoring or support would I have during and after each session?
4Because this trial is specifically enrolling people with major depressive disorder and tracking suicidal ideation as a primary outcome, should I be concerned that the treatment itself could affect suicide risk, and how would that be monitored throughout the study?
5What would happen to my regular depression treatment if I joined this trial — would I need to stop any current medications, and what's the plan if my symptoms get significantly worse during the study?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score (Antidepressant efficacy)

Timeframe: Baseline and Day 7 (D7) after the dosing session

Incidence of Suicidal Ideation and Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

Timeframe: Day 1 post-intervention

Trial details

NCT IDNCT07562191

SponsorUniversidade Federal do Rio Grande do Norte

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-02-01

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