Major Depression DisorderPhase 1DMT-BolusNCT06671977
Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans
A Phase 1 study testing DMT-Medium Dose, DMT-Low Dose and THC-Medium Dose in people with Major Depression Disorder and Depression, run by Deepak C. D'Souza at 1 site in United States.
Trial summary
The goal of this phase 1 study is to investigate the safety and efficacy of dimethyltryptamine (DMT) in individuals with depression and healthy controls. We hypothesize that administration of DMT will result in decreases in depression, associated symptoms, and neuroplastic changes in depressed subjects. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depression Disorder, Depression
- What is being tested?
- DMT-Medium Dose, DMT-Low Dose and THC-Medium Dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Mar 2025to 1 Dec 2027
- 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
Some Common Inclusion Criteria:
- Males and females
- Age 21 to 65 years
- Body mass index between 18-35 kg/m2
- Willing to refrain from taking any medications not approved by the study physician
- Willing to refrain from using street drugs and alcohol
- Negative urine drug screen
- Willing and able to abstain from smoking throughout each test session
- Women who are of child-bearing potential (WOCBP) and sexually active must be willing to practice an effective means of birth control
- Willing not to drive to and from the testing session
Some Inclusion Criteria for Subjects with MDD:
- Diagnosed with Major Depressive Disorder (MDD)
- Unsatisfactory response to antidepressants
- Engaged in treatment for depression with a clinician and willing to continue treatment for the duration of the study
- Not engaged in treatment
- Consent to allow the research team to communicate with mental health provider.
- Only subjects who get support for participation in the trial from their mental health clinician will be eligible to be enrolled in the study
Some Common Exclusion Criteria:
- Medications that might significantly interfere with the effects of the study medications
- Cognitive dysfunction that could interfere with study participation
- Alcohol or substance use disorder
- Any lifetime history of hallucinogen use disorder
- Regular use or misuse of hallucinogens
- History of intolerance to perceptual altering drugs
- Significant blood pressure problems
- Pregnancy or currently breast feeding (lactation)
- Any unstable medical conditions
- Significant cardiovascular disease
- Significantly abnormal laboratory test results
- History of serotonin syndrome
Some Exclusion criteria for MDD subjects:
- Current primary psychiatric disorder other than MDD
- Medically significant condition rendering unsuitability for the study
Some Exclusion criteria for healthy controls:
- No current DSM-V psychiatric disorder, excluding nicotine and caffeine use disorder
- No family history of serious mental illness (e.g., schizophrenia, bipolar disorder)
Some Inclusion criteria for healthy controls:
- No current DSM-5 psychiatric disorder, excluding nicotine and caffeine use disorder
- No lifetime use of psychiatric medication >3 months (proxy for psychiatric disorders)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Biological Studies Unit at the VA Connecticut Healthcare System, Yale School of Medicine,
West Haven, Connecticut, 06516
Deepak C D'Souza, MD, 203-932-5711 ext. 14495, deepak.dsouza@yale.edu
About this study
Official title: Phase 1 Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans
The goal of this phase 1 study is to investigate the safety and efficacy of dimethyltryptamine (DMT) in individuals with depression and healthy controls. We hypothesize that administration of DMT will result in decreases in depression, associated symptoms, and neuroplastic changes in depressed subjects. We expect that DMT will induce changes in neuroplasticity as indexed using electroencephalographic (EEG) measures and tasks in both depressed individuals and healthy volunteers, though to different degrees. 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 Depression Disorder, Depression
- Being tested
- DMT-Medium Dose, DMT-Low Dose, THC-Medium Dose, THC-Low Dose
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DMT-Medium DoseDrug
14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.
DMT-Low DoseDrug
10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes
THC-Medium DoseDrug
0.5 mg over 5 minutes and then 2 mg over and 55 minutes
THC-Low DoseDrug
0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes
| Study group | Role | What they receive |
|---|---|---|
| 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes | Active comparator | Low dose DMT Receives: Drug: DMT-Low Dose |
| 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes. | Active comparator | Medium Dose DMT Receives: Drug: DMT-Medium Dose |
| 0.5 mg over 5 minutes and then 2 mg over and 55 minutes | Active comparator | THC-Medium Dose Receives: Drug: THC-Medium Dose |
| Placebo | Placebo comparator | Not described Receives: Drug: DMT-Medium Dose; Drug: DMT-Low Dose; Drug: THC-Medium Dose; Drug: THC-Low Dose |
| 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes | Active comparator | Low Dose THC Receives: Drug: THC-Low Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Physiological indices
Pulse oximetry will be measured continuously.
Measured: Time Frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration]blood pressure and heart rate will be measured before, during, and after the dosing on each test day.
Psychedelic Effects
The 30-item revised Mystical Experience Questionnaire (MEQ30) will be used to measure mystical/psychedelic experiences associated with drugs like psilocybin
Measured: From start Test Day Time points (Minutes): -60, +30, +120.
Psychotomimetic Effects
To capture the effects of DMT/THC/placebo on perception, thought, and sensory processing, participants will be measured using the Psychotomimetic States Inventory
Measured: Test Day Time points (Minutes): -60, +30, +120
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 anxiety.
Measured: Test Day Time points (Minutes): -60, +30, +120
Depression
subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture the depression.
Measured: From start of test day (-60), +30, and +120.
Intensity of the Experience
The Challenging Experience Questionnaire (CEQ) a 26 item likert-scale style survey will be used to provide a phenomenological profile specifically of challenging aspects of experiences with psilocybin
Measured: Test Day Time points (Minutes): +150 - +180
Drug Reinforcing Effects
Will be assessed with questions such as:
- How likely are you to use this drug recreationally? 0 (not at all) ------------------------100 (most of all)
- How much are you willing to pay for the acute effects that you experienced during the dosing session? $0-------------------$100 Shortly after resolution of effects, participants will be instructed to retroactively rate the highest effects experienced since the last time they were prompted to provide a rating.
Measured: Test Day Time points (Minutes): +120
Tolerability of Overt Adverse Effects
Tolerability defined by the US FDA as "the degree to which overt adverse effects can be tolerated" by a subject was assessed [60]. At the end of the test day, after all drug effects have worn off, participants will be asked to score 1) the overall experience on a visual analog scale [VAS] (0 = intolerable to 100 = well-tolerated).
Measured: Test Day Time points (Minutes): -60, +30, +120, 180 (end of test day)
Electrophysiological
Measured: Resting State EEG: Will be collected the day after each dosing session. [Time Frame: -60 minutes before DMT administration until +180 minutes after DMT administration].
Secondary outcomes (5)
Expectancy Effects
Measured: Subjects will be tested for expectancy effects at screening, and before each dosing session.
Adequacy of blinding
Subjects will be asked to guess their treatment assignment, the degree of certainty of their guess and the reason for their guess both immediately after the psychedelic dosing session(s) and at the end of the study. Either the James' blinding index (BI) or Bang's BI, will be used to measure the adequacy of the blind.
Measured: Time Frame: 0; immediately after DMT administration, and +180 minutes at the end of the study
Blood
Measured: Blood sample measurements will be repeated approximately 0, 20, 30, and 60 minutes after drug administration
Changes in personality domains (NEO personality inventory)
Measured: [Time Frame: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration]
Psychological Flexibility
The Acceptance and Action Questionnaire (AAQ) is a one-factor, likert scale assessment of psychological inflexibility
Measured: Time Frame: +180 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 posted4 Nov 2024
- Study start14 Mar 2025
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depression DisorderStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Crossover
- Model description
- Healthy individuals and individuals with current major depression will participate in 2 dosing sessions separated by 4 weeks, during which they will receive placebo, low dose DMT, medium dose DMT, low dose THC and medium dose THC. Subjects will be prepared for the dosing session and also debriefed after each dosing session
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Deepak C. D'Souza
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Deepak C. D'Souza, Yale University
- Investigators
- Deepak D'Souza, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06671977
- Sponsor's protocol ID
- 2000034770
- Acronym
- DMT-Bolus
- Status last verified
- Jun 2026
- First submitted
- 16 Oct 2024
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans
- ClinicalTrials.gov ID
- NCT06671977
- Acronym / sponsor ID
- DMT-Bolus / 2000034770
- Conditions
- Major Depression Disorder, Depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Deepak C. D'SouzaUniversity, hospital or other
- Study start
- 14 Mar 2025 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 4 Nov 2024 (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 phase 1 study is to investigate the safety and efficacy of dimethyltryptamine (DMT) in individuals with depression and healthy controls. We hypothesize that administration of DMT will result in decreases in depression, associated symptoms, and neuroplastic changes in depressed subjects. We expect that DMT will induce changes in neuroplasticity as indexed using electroencephalographic (EEG) measures and tasks in both depressed individuals and healthy volunteers, though to different degrees. 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
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 5
- Model description
- Healthy individuals and individuals with current major depression will participate in 2 dosing sessions separated by 4 weeks, during which they will receive placebo, low dose DMT, medium dose DMT, low dose THC and medium dose THC. Subjects will be prepared for the dosing session and also debriefed after each dosing session
| Arm | Type | Receives |
|---|---|---|
| 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes | Active comparator | Drug: DMT-Low DoseLow dose DMT |
| 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes. | Active comparator | Drug: DMT-Medium DoseMedium Dose DMT |
| 0.5 mg over 5 minutes and then 2 mg over and 55 minutes | Active comparator | Drug: THC-Medium DoseTHC-Medium Dose |
| Placebo | Placebo comparator | Drug: DMT-Medium Dose, Drug: DMT-Low Dose, Drug: THC-Medium Dose, Drug: THC-Low Dose |
| 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes | Active comparator | Drug: THC-Low DoseLow Dose THC |
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 |
|---|---|---|
| DMT-Medium Dose14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes. | Drug | 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes., Placebo |
| DMT-Low Dose10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes | Drug | 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes, Placebo |
| THC-Medium Dose0.5 mg over 5 minutes and then 2 mg over and 55 minutes | Drug | 0.5 mg over 5 minutes and then 2 mg over and 55 minutes, Placebo |
| THC-Low Dose0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes | Drug | 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes, Placebo |
Primary outcome
Safety of Physiological indices
Time frame: Time Frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration]blood pressure and heart rate will be measured before, during, and after the dosing on each test day.
Pulse oximetry will be measured continuously.
Psychedelic Effects
Time frame: From start Test Day Time points (Minutes): -60, +30, +120.
The 30-item revised Mystical Experience Questionnaire (MEQ30) will be used to measure mystical/psychedelic experiences associated with drugs like psilocybin
Psychotomimetic Effects
Time frame: Test Day Time points (Minutes): -60, +30, +120
To capture the effects of DMT/THC/placebo on perception, thought, and sensory processing, participants will be measured using the Psychotomimetic States Inventory
Anxiety
Time frame: Test Day Time points (Minutes): -60, +30, +120
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 anxiety.
Depression
Time frame: From start of test day (-60), +30, and +120.
subjects will be asked to score from 0 (not at all) to 100 (worst ever) to capture the depression.
Intensity of the Experience
Time frame: Test Day Time points (Minutes): +150 - +180
The Challenging Experience Questionnaire (CEQ) a 26 item likert-scale style survey will be used to provide a phenomenological profile specifically of challenging aspects of experiences with psilocybin
Drug Reinforcing Effects
Time frame: Test Day Time points (Minutes): +120
Will be assessed with questions such as: * How likely are you to use this drug recreationally? 0 (not at all) ------------------------100 (most of all) * How much are you willing to pay for the acute effects that you experienced during the dosing session? $0-------------------$100 Shortly after resolution of effects, participants will be instructed to retroactively rate the highest effects experienced since the last time they were prompted to provide a rating.
Tolerability of Overt Adverse Effects
Time frame: Test Day Time points (Minutes): -60, +30, +120, 180 (end of test day)
Tolerability defined by the US FDA as "the degree to which overt adverse effects can be tolerated" by a subject was assessed [60]. At the end of the test day, after all drug effects have worn off, participants will be asked to score 1) the overall experience on a visual analog scale [VAS] (0 = intolerable to 100 = well-tolerated).
Electrophysiological
Time frame: Resting State EEG: Will be collected the day after each dosing session. [Time Frame: -60 minutes before DMT administration until +180 minutes after DMT administration].
5 secondary outcomes
Expectancy Effects
Time frame: Subjects will be tested for expectancy effects at screening, and before each dosing session.
Adequacy of blinding
Time frame: Time Frame: 0; immediately after DMT administration, and +180 minutes at the end of the study
Blood
Time frame: Blood sample measurements will be repeated approximately 0, 20, 30, and 60 minutes after drug administration
Changes in personality domains (NEO personality inventory)
Time frame: [Time Frame: -60 minutes before DMT administration; 0, +30, and +60 minutes after DMT administration]
Psychological Flexibility
Time frame: Time Frame: +180 minutes after DMT administration
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 16 Jun 2026.
- Individual participant dataSharing planned: No
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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.
Deepak D'Souza, MD principal investigator
Yale University
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 DMT-Medium Dose, DMT-Low Dose and THC-Medium Dose in people with Major Depression Disorder and Depression, run by Deepak C. D'Souza 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: looking for participants now, as of the sponsor's last update on 16 Jun 2026. 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. Some participants in this study may receive a placebo. 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?
Contact Deepak C D'Souza, MD ((203) 932-5711 ext. x12594, deepak.dsouza@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Physiological indices (time frame: Time Frame: -60 and -30 minutes before DMT administration; 0, +5, +10, +15, +20, +30, +45, +60, and +120 minutes after DMT administration]blood pressure and heart rate will be measured before, during, and after the dosing on each test day.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2026.