Randomized, Double-Blind, Placebo-Controlled Phase IIb Trial of Inhaled N,N-Dimethyltryptamine (DMT) for Major Depressive Disorder
Status: Recruiting
Location: See all (5) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
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.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:
• 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
Locations
Other Locations
Brazil
Hospital de Saúde Mental Professor Frota Pinto
NOT_YET_RECRUITING
Fortaleza
Hospital Universitário Onofre Lopes - HUOL - UFRN
RECRUITING
Natal
Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro (IPUB-UFRJ)
NOT_YET_RECRUITING
Rio De Janeiro
Complexo Hospitalar Universitário Professor Edgard Santos, Federal University of Bahia (HUPES-UFBA)
NOT_YET_RECRUITING
Salvador
Instituto de Psiquiatria - Hospital das Clínicas - IPq - HC - USP
NOT_YET_RECRUITING
São Paulo
Time Frame
Start Date:2026-08-01
Estimated Completion Date:2027-08-01
Participants
Target number of participants:140
Treatments
Experimental: High-Dose DMT → Remitters (No Re-dosing)
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.
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.
Active_comparator: Low-Dose DMT → Remitters (No Re-dosing)
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.
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.