Inhaled DMT for Major Depressive Disorder
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversidade Federal do Rio Grande do Norte
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
N,N-Dimethyltryptamine (15 mg + 60 mg)
DrugInhaled 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).
N,N-Dimethyltryptamine (1 mg + 4 mg)
DrugInhaled 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).
Treatment groups
140 Participants
are divided into 4 treatment groupsGroup A: High-Dose DMT → Remitters (No Re-dosing)Experimental treatment 1 intervention
Group B: High-Dose DMT → Non-Remitters (Open-Label Re-dosing)Experimental treatment 1 intervention
Group C: Low-Dose DMT → Remitters (No Re-dosing)Active comparator 1 intervention
Group D: Low-Dose DMT → Non-Remitters (Open-Label Re-dosing)Active comparator 2 interventions
Trial outcomes
Primary outcomes
1
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).
Time frame
Baseline and Day 7 (D7) after the dosing sessionSecondary outcomes
1
Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS is a clinician-rated scale to monitor depression severity. Total score ranges from 0 to 60. Higher scores indicate greater severity of depression (worse outcome). This measure will assess the durability of the antidepressant effect in participants who achieved remission.
Time frame
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-intervention2
Number and proportion of adverse events (AEs)
AEs defined by CTCAE v5.0, occurring after DMT administration and compared between study arms across assessment time points.
Time frame
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-intervention3
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.
Time frame
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-intervention4
Change from Baseline in the Montgomery-Åsberg Depression Rating Scale - Suicidal Ideation (MADRS-SI, Item 10) Score (Antisuicidal efficacy)
This is a single item (Item 10) from the MADRS scale that specifically evaluates suicidal ideation. The score ranges from 0 to 6. Higher scores indicate greater severity of suicidal thoughts (worse outcome).
Time frame
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-interventionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Universidade Federal do Rio Grande do Norte
Lead sponsor
Financiadora de Estudos e Projetos
Collaborator
Source ClinicalTrials.gov