Inhaled DMT for Major Depressive Disorder

NCT07562191 | Not Yet Recruiting Phase 2

• 2 other identifiers: UFRN-DMT-MDD-IIb-2026FINEP-0366/24
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

MDD; Major Depressive Disorder (MDD); Major Depression; Suicidal Ideation; Suicide

Keywords

DMT; major depressive disorder; N,N-dimethyltryptamine; psychedelic therapy; inhaled DMT; vaporized DMT; suicidality; non invasive

Outcome Measures

Primary Outcomes (2)

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

  The MADRS is a clinician-rated scale used to evaluate the severity of depressive symptoms. It consists of 10 items, each rated from 0 to 6. The total score ranges from 0 to 60. Higher scores indicate greater severity of depression (worse outcome).

  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)

  The C-SSRS is a standardized tool used to evaluate the occurrence, severity, and intensity of suicidal ideation and behavior. It assesses 5 levels of ideation (from "wish to be dead" to "active ideation with specific plan and intent") and 5 types of suicidal behavior. Results are reported as the number of participants who endorse any suicidal ideation or behavior (Yes/No) during the assessment period.

  Day 1 post-intervention

Secondary Outcomes (61)

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

  Baseline (pre-DMT session), 150 minutes post-DMT session (Day 0), Day 1, Day 7, Day 14, 1 month, 3 months, and 12 months post-intervention

• Number and proportion of adverse events (AEs)

  Baseline (pre-DMT session), 150 minutes post-DMT session (Day 0), Day 1, Day 7, Day 14, 1 month, 3 months, and 12 months post-intervention

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

  Baseline (pre-DMT session), 150 minutes post-DMT session (Day 0), Day 1, Day 7, Day 14, 1 month, 3 months, and 12 months post-intervention

• Change from Baseline in the Montgomery-Åsberg Depression Rating Scale - Suicidal Ideation (MADRS-SI, Item 10) Score (Antisuicidal efficacy)

  Baseline (pre-DMT session), 150 minutes post-DMT session (Day 0), Day 1, Day 7, Day 14, 1 month, 3 months, and 12 months post-intervention

• Change from Baseline in the Beck Scale for Suicide Ideation (BSI) Total Score

  Baseline (pre-DMT session), 150 minutes post-DMT session (Day 0), Day 1, Day 7, Day 14, 1 month, 3 months, and 12 months post-intervention

Study Arms (4)

High-Dose DMT → Remitters (No Re-dosing)

EXPERIMENTAL

Participants randomized to the high-dose DMT group (15 mg followed by 60 mg on Day 0) who achieve remission at Day 7 (MADRS ≤10) receive no further dosing and enter long-term follow-up.

Drug: N,N-Dimethyltryptamine (15 mg + 60 mg)

High-Dose DMT → Non-Remitters (Open-Label Re-dosing)

EXPERIMENTAL

Participants randomized to the high-dose DMT group (15 mg followed by 60 mg on Day 0) who do not achieve remission at Day 7 (MADRS \>10) receive an additional open-label high-dose session (15 mg followed by 60 mg) on Day 14 (±3 days), followed by long-term follow-up.

Drug: N,N-Dimethyltryptamine (15 mg + 60 mg)

Low-Dose DMT → Remitters (No Re-dosing)

ACTIVE COMPARATOR

Participants randomized to the low-dose DMT group (1 mg followed by 4 mg on Day 0) who achieve remission at Day 7 (MADRS ≤10) receive no further dosing and enter long-term follow-up.

Drug: N,N-Dimethyltryptamine (1 mg + 4 mg)

Low-Dose DMT → Non-Remitters (Open-Label Re-dosing)

ACTIVE COMPARATOR

Participants randomized to the low-dose DMT group (1 mg followed by 4 mg on Day 0) who do not achieve remission at Day 7 (MADRS \>10) receive an open-label high-dose session (15 mg followed by 60 mg) on Day 14 (±3 days), followed by long-term follow-up.

Drug: N,N-Dimethyltryptamine (15 mg + 60 mg); Drug: N,N-Dimethyltryptamine (1 mg + 4 mg)

Interventions

N,N-Dimethyltryptamine (15 mg + 60 mg) DRUG

Inhaled N,N-dimethyltryptamine (DMT) administered via a Volcano Medic 2 vaporizer in two inhalations 1 hour apart, using a high-dose regimen (15 mg + 60 mg).

Also known as: N,N-dimethyltryptamine, DMT

High-Dose DMT → Non-Remitters (Open-Label Re-dosing); High-Dose DMT → Remitters (No Re-dosing); Low-Dose DMT → Non-Remitters (Open-Label Re-dosing)

N,N-Dimethyltryptamine (1 mg + 4 mg) DRUG

Inhaled N,N-dimethyltryptamine (DMT) administered via a Volcano Medic 2 vaporizer in two inhalations 1 hour apart, using a low-dose regimen (1 mg + 4 mg).

Also known as: N,N-Dimethyltryptamine, DMT

Low-Dose DMT → Non-Remitters (Open-Label Re-dosing); Low-Dose DMT → Remitters (No Re-dosing)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 discontinued at least 14 days prior to dosing
• Psychedelic trial participation in past 12 months

Sponsors & Collaborators

• Financiadora de Estudos e Projetos: collaborator
• Universidade Federal do Rio Grande do Norte: lead

Study Sites (5)

Hospital de Saúde Mental Professor Frota Pinto

Fortaleza, Ceará, Brazil

Location

Complexo Hospitalar Universitário Professor Edgard Santos, Federal University of Bahia (HUPES-UFBA)

Salvador, Estado de Bahia, Brazil

Location

Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro (IPUB-UFRJ)

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Hospital Universitário Onofre Lopes - HUOL - UFRN

Natal, Rio Grande do Norte, Brazil

Location

Instituto de Psiquiatria - Hospital das Clínicas - IPq - HC - USP

São Paulo, São Paulo, Brazil

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Suicidal Ideation; Suicide

Interventions

N,N-Dimethyltryptamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Full Professor at Brain Institute (Instituto do Cérebro - ICe), Federal University of Rio Grande do Norte (UFRN)

Model Details: This is a multicenter Phase 2, randomized, quadruple-blind, parallel-group clinical trial with an open-label extension. In Stage 1, participants are randomized 1:1 to 1 of 2 treatment arms: a high-dose inhaled DMT regimen (15 mg followed 1 hour later by 60 mg) or a low-dose inhaled DMT regimen used as an active comparator (1 mg followed 1 hour later by 4 mg). Participants who achieve remission at Day 7 (MADRS ≤10) continue follow-up only. Participants who do not achieve remission at Day 7 (MADRS \>10), regardless of initial assignment, enter Stage 2, an open-label extension in which they receive the high-dose DMT regimen on Day 14 (±3 days), followed by continued follow-up.

Study Record Dates

• First Submitted: March 27, 2026
• First Posted: May 1, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data and supporting documents will be available beginning 12 months after publication of the primary results. There is no predefined end date for data availability.
• Access Criteria: Access to deidentified individual participant data and supporting documents will be granted to researchers who provide a methodologically sound research proposal. Requests will be reviewed by the study investigators and sponsoring institution. Data will be shared for purposes consistent with the approved proposal, subject to institutional review, ethical approvals when applicable, and execution of a data use agreement. Access will be provided through secure transfer mechanisms to ensure data confidentiality and compliance with applicable regulations.

Locations

BR (5)