Major Depressive DisorderPhase 1NCT04711915
Fixed Order, Open-Label, Dose-Escalation Study of DMT in Humans
A Phase 1 study testing 0.1 mg/kg Dimethyltryptamine (DMT) and 0.3 mg/kg Dimethyltryptamine (DMT) in people with Major Depressive Disorder and Depression, run by Yale University at 1 site in United States.
Trial summary
The goal of this fixed order, open-label, dose-escalation study is to investigate the safety and efficacy of specific doses of dimethyltryptamine (DMT) in humans. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Depression
- What is being tested?
- 0.1 mg/kg Dimethyltryptamine (DMT) and 0.3 mg/kg Dimethyltryptamine (DMT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2021to 1 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Healthy controls inclusion criteria:
- Medically healthy
- Psychiatrically healthy
Healthy controls exclusion criteria:
- Unstable medical conditions
- Psychiatric illness
Depression inclusion criteria:
- Medically healthy
- Diagnosis of major depressive disorder
Depression exclusion criteria:
-Unstable medical conditions
Trial locations and contacts
1 site in 1 country.
United States1 site
Biological Studies Unit at the VA Connecticut Healthcare System, Yale School of Medicine
West Haven, Connecticut, 06516
About this study
The goal of this fixed order, open-label, dose-escalation study is to investigate the safety and efficacy of specific doses of dimethyltryptamine (DMT) in humans.
Read the detailed description
The results of this study will inform the doses to be used in a larger, double-blind, randomized, placebo-controlled, crossover study. Since the goal of the open label study is to inform the double-blind, randomized, placebo-controlled study, the investigators are citing the hypothesis of the latter solely for providing context. The investigators hypothesize that the administration of DMT will result in neuroplastic changes in healthy and depressed subjects. These changes in neuroplasticity will be indexed using electroencephalographic (EEG) measures and tasks. These neuronal changes may in parallel cause changes in mood measured both in healthy and depressed subjects, which will be captured using appropriate psychometric measures of mood.
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- 0.1 mg/kg Dimethyltryptamine (DMT), 0.3 mg/kg Dimethyltryptamine (DMT)
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.1 mg/kg Dimethyltryptamine (DMT)Drug
Also called Low Dose DMT
0.1 mg/kg DMT
0.3 mg/kg Dimethyltryptamine (DMT)Drug
Also called Moderate Dose DMT
0.3 mg/kg DMT
| Study group | Role | What they receive |
|---|---|---|
| 0.1 mg/kg DMT | Active comparator | 0.1 mg/kg DMT administered intravenously Receives: Drug: 0.1 mg/kg Dimethyltryptamine (DMT) |
| 0.3 mg/kg DMT | Active comparator | 0.3 mg/kg DMT administered intravenously Receives: Drug: 0.3 mg/kg Dimethyltryptamine (DMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Blood Pressure
Systolic and diastolic blood pressure will be measured before and several times after the administration of DMT on each test day.
Measured: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration
Change in Heart Rate
Heart rate will be measured before and several times after the administration of DMT on each test day.
Measured: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration
Change in Psychedelic Effects
The modified Altered States of Consciousness Rating Scale (ASC) will be used to assess drug-induced altered states of consciousness before and several times after drug administration. This is a 23-item subjective rating scale that will be completed using a visual analog scale format. Questions are scored 0 to 100 each; higher numbers indicate greater psychedelic effects.
Measured: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration
Change in Anxiety
Anxiety will be assessed using a visual analog scale that subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture the net anxiety produced by DMT. This will be collected before and several times after DMT administration.
Measured: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration
Drug Reinforcing Effects
Subjects will be asked to answer questions such as (1) How likely are you to use this drug? and (2) How much are you willing to pay for this experience? using a visual analog scale.
Measured: +120 minutes after DMT administration
Overall Tolerability assessed by the VAS
Overall tolerability will be assessed using a visual analog scale that subjects will be asked to score from 0 (well tolerated) to 100 (intolerable) to capture the net tolerability of DMT.
Measured: +120 minutes after DMT administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2021
- Study start17 Mar 2021
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Healthy individuals and patients with major depressive disorder will participate in this study. Subjects will receive 0.1 mg/kg and 0.3 mg/kg DMT in a fixed order across 2 test days.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deepak C. D'Souza, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04711915
- Sponsor's protocol ID
- 2000027720
- Status last verified
- Jul 2025
- First submitted
- 12 Jan 2021
- Last updated
- 3 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Swieczkowski D, Kwasny A, Cubala WJ. Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jul 13;140:111419. doi: 10.1016/j.pnpbp.2025.111419. Epub 2025 Jun 7.
PubMed 40484114
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fixed Order, Open-Label, Dose-Escalation Study of DMT in Humans
- ClinicalTrials.gov ID
- NCT04711915
- Acronym / sponsor ID
- 2000027720
- Conditions
- Major Depressive Disorder, Depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 17 Mar 2021 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 15 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this fixed order, open-label, dose-escalation study is to investigate the safety and efficacy of specific doses of dimethyltryptamine (DMT) in humans.
Detailed description
The results of this study will inform the doses to be used in a larger, double-blind, randomized, placebo-controlled, crossover study. Since the goal of the open label study is to inform the double-blind, randomized, placebo-controlled study, the investigators are citing the hypothesis of the latter solely for providing context. The investigators hypothesize that the administration of DMT will result in neuroplastic changes in healthy and depressed subjects. These changes in neuroplasticity will be indexed using electroencephalographic (EEG) measures and tasks. These neuronal changes may in parallel cause changes in mood measured both in healthy and depressed subjects, which will be captured using appropriate psychometric measures of mood.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Healthy individuals and patients with major depressive disorder will participate in this study. Subjects will receive 0.1 mg/kg and 0.3 mg/kg DMT in a fixed order across 2 test days.
| Arm | Type | Receives |
|---|---|---|
| 0.1 mg/kg DMT | Active comparator | Drug: 0.1 mg/kg Dimethyltryptamine (DMT)0.1 mg/kg DMT administered intravenously |
| 0.3 mg/kg DMT | Active comparator | Drug: 0.3 mg/kg Dimethyltryptamine (DMT)0.3 mg/kg DMT administered intravenously |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0.1 mg/kg Dimethyltryptamine (DMT)Also: Low Dose DMT0.1 mg/kg DMT | Drug | 0.1 mg/kg DMT |
| 0.3 mg/kg Dimethyltryptamine (DMT)Also: Moderate Dose DMT0.3 mg/kg DMT | Drug | 0.3 mg/kg DMT |
Primary outcome
Change in Blood Pressure
Time frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration
Systolic and diastolic blood pressure will be measured before and several times after the administration of DMT on each test day.
Change in Heart Rate
Time frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration
Heart rate will be measured before and several times after the administration of DMT on each test day.
Change in Psychedelic Effects
Time frame: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration
The modified Altered States of Consciousness Rating Scale (ASC) will be used to assess drug-induced altered states of consciousness before and several times after drug administration. This is a 23-item subjective rating scale that will be completed using a visual analog scale format. Questions are scored 0 to 100 each; higher numbers indicate greater psychedelic effects.
Change in Anxiety
Time frame: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration
Anxiety will be assessed using a visual analog scale that subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture the net anxiety produced by DMT. This will be collected before and several times after DMT administration.
Drug Reinforcing Effects
Time frame: +120 minutes after DMT administration
Subjects will be asked to answer questions such as (1) How likely are you to use this drug? and (2) How much are you willing to pay for this experience? using a visual analog scale.
Overall Tolerability assessed by the VAS
Time frame: +120 minutes after DMT administration
Overall tolerability will be assessed using a visual analog scale that subjects will be asked to score from 0 (well tolerated) to 100 (intolerable) to capture the net tolerability of DMT.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
- Derived from this study: PubMed 40484114Swieczkowski D, Kwasny A, Cubala WJ. Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jul 13;140:111419. doi: 10.1016/j.pnpbp.2025.111419. Epub 2025 Jun 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 0.1 mg/kg Dimethyltryptamine (DMT) and 0.3 mg/kg Dimethyltryptamine (DMT) in people with Major Depressive Disorder and Depression, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Blood Pressure (time frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04711915, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.