Actively Recruiting
Randomized, Double-Blind, Placebo-Controlled Phase IIb Trial of Inhaled N,N-Dimethyltryptamine (DMT) for Major Depressive Disorder
Led by Universidade Federal do Rio Grande do Norte · Updated on 2026-05-28
140
Participants Needed
5
Research Sites
25 weeks
Total Duration
On this page
Sponsors
U
Universidade Federal do Rio Grande do Norte
Lead Sponsor
F
Financiadora de Estudos e Projetos
Collaborating Sponsor
AI-Summary
What this Trial Is About
This research aims to evaluate the effects of inhaled N,N-dimethyltryptamine (DMT) in adults with Major Depressive Disorder (MDD), a condition marked by persistent depressive symptoms and suicide risk. The trial, a Phase 2b, randomized, double-blind, active-controlled study, compares the rapid antidepressant and antisuicidal potential of inhaled DMT at different doses. It addresses the need for faster-acting treatments with fewer side effects than current options, recruiting 140 adults with moderate to severe depression and a stable treatment history. Participants are randomly assigned to receive either a high-dose inhaled DMT regimen (15 mg followed 1 hour later by 60 mg) or a low-dose active comparator (1 mg followed 1 hour later by 4 mg), both administered via a vaporizer in two inhalations one hour apart. Those who do not reach remission by Day 7 enter an open-label extension and receive a high-dose DMT session on Day 14 (plus or minus 3 days). Participants who achieve remission at Day 7 proceed directly to long-term follow-up. Throughout the study, participants undergo evaluations including depression and suicidality scales, safety monitoring, and quality-of-life assessments up to 12 months after treatment. Researchers track changes in depression severity using the MADRS scale and suicidal ideation measures shortly after dosing and at multiple follow-up points. The study also collects various biological and psychological data to understand treatment effects and safety over time.
CONDITIONS
Brief Title
Inhaled DMT for Major Depressive Disorder
Who Can Participate
Eligibility Criteria
You may qualify if you...
- 18 years or older, capable of making decisions, and able to provide informed consent
- Diagnosed with 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 Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher
- No changes in treatment, including antidepressants, in the 4 weeks prior to the study
- Abstain from psychedelics for at least 14 days before dosing and during the 12-month follow-up
You will not qualify if you...
- Major cardiac, liver, or kidney disease; unstable cardiovascular conditions
- Uncontrolled high blood pressure, QTc prolongation, arrhythmias, or heart valve disease
- Chronic lung conditions such as COPD or asthma
- Severe obesity, uncontrolled diabetes, blood clotting disorders, thyroid disease, or glaucoma
- Neurological risks like aneurysm, increased intracranial pressure, epilepsy, or severe neurological disorders
- Deficiency of monoamine oxidase (MAO) or history of serotonin syndrome
- Pregnant, breastfeeding, positive pregnancy test, or lack of effective contraception
- Secondary depression
- Cluster B personality disorders including borderline personality disorder with two or more suicidal behaviors in the past year or poor therapeutic rapport
- Psychotic disorders, MDD with psychotic features, or first-degree family history of psychosis or bipolar disorder
- Mania or hypomania with a Young Mania Rating Scale (YMRS) score of 8 or higher
- Obsessive-compulsive disorder, dissociative disorders, active post-traumatic stress disorder, or decompensated eating disorders
- Moderate to severe substance use disorder in the past 6 months, except nicotine or caffeine
- Lifetime use disorder of ketamine, PCP, psychedelics, or MDMA
- Current use of MAO inhibitors unless stopped at least 14 days before dosing
- Participation in a psychedelic trial within the past 12 months
- Cognitive impairment that affects valid assessment of study measures
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 14 days
Participants receive inhaled N,N-Dimethyltryptamine (DMT) in a randomized, double-blind design with either a high-dose or low-dose regimen on Day 0. Non-remitters at Day 7 may receive an additional open-label high-dose session around Day 14.
1 dosing visit on Day 0 and 1 possible re-dosing visit around Day 14 (±3 days)
Duration - Up to 12 months
Participants are followed for up to 12 months after treatment to assess depression, suicidality, safety, functioning, quality of life, and other psychological measures.
Multiple follow-up visits through Month 12
Trial Site Locations
Total: 5 locations
1
Hospital de Saúde Mental Professor Frota Pinto
Fortaleza, Ceará, Brazil
Not Yet Recruiting
2
Complexo Hospitalar Universitário Professor Edgard Santos, Federal University of Bahia (HUPES-UFBA)
Salvador, Estado de Bahia, Brazil
Not Yet Recruiting
3
Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro (IPUB-UFRJ)
Rio de Janeiro, Rio de Janeiro, Brazil
Not Yet Recruiting
4
Hospital Universitário Onofre Lopes - HUOL - UFRN
Natal, Rio Grande do Norte, Brazil
Actively Recruiting
5
Instituto de Psiquiatria - Hospital das Clínicas - IPq - HC - USP
São Paulo, São Paulo, Brazil
Not Yet Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
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