Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans (DMT-Bolus)

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.

Study Overview

• Status: Recruiting
• Conditions: Depression; Major Depression Disorder
• Intervention / Treatment: Drug: DMT-Low Dose; Drug: DMT-Medium Dose; Drug: THC-Medium Dose; Drug: THC-Low Dose

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Deepak C D'Souza, MD; Phone Number: x12594 (203) 932-5711; Email: deepak.dsouza@yale.edu

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Recruiting
      • Biological Studies Unit at the VA Connecticut Healthcare System, Yale School of Medicine,
      • Contact: Deepak C D'Souza, MD; Phone Number: 14495 203-932-5711; Email: deepak.dsouza@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Some Common Inclusion Criteria:

1. Males and females
2. Age 21 to 65 years
3. Body mass index between 18-35 kg/m2
4. Willing to refrain from taking any medications not approved by the study physician
5. Willing to refrain from using street drugs and alcohol
6. Negative urine drug screen
7. Willing and able to abstain from smoking throughout each test session
8. Women who are of child-bearing potential (WOCBP) and sexually active must be willing to practice an effective means of birth control
9. Willing not to drive to and from the testing session

Some Inclusion Criteria for Subjects with MDD:

1. Diagnosed with Major Depressive Disorder (MDD)
2. Unsatisfactory response to antidepressants
3. Engaged in treatment for depression with a clinician and willing to continue treatment for the duration of the study
4. Not engaged in treatment
5. Consent to allow the research team to communicate with mental health provider.
6. 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:

1. Medications that might significantly interfere with the effects of the study medications
2. Cognitive dysfunction that could interfere with study participation
3. Alcohol or substance use disorder
4. Any lifetime history of hallucinogen use disorder
5. Regular use or misuse of hallucinogens
6. History of intolerance to perceptual altering drugs
7. Significant blood pressure problems
8. Pregnancy or currently breast feeding (lactation)
9. Any unstable medical conditions
10. Significant cardiovascular disease
11. Significantly abnormal laboratory test results
12. History of serotonin syndrome

Some Exclusion criteria for MDD subjects:

1. Current primary psychiatric disorder other than MDD
2. Medically significant condition rendering unsuitability for the study

Some Exclusion criteria for healthy controls:

1. No current DSM-V psychiatric disorder, excluding nicotine and caffeine use disorder
2. No family history of serious mental illness (e.g., schizophrenia, bipolar disorder)

Some Inclusion criteria for healthy controls:

1. No current DSM-5 psychiatric disorder, excluding nicotine and caffeine use disorder
2. No lifetime use of psychiatric medication >3 months (proxy for psychiatric disorders)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: DMT-Low Dose; 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes; Drug: DMT-Medium Dose; 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.; Drug: THC-Medium Dose; 0.5 mg over 5 minutes and then 2 mg over and 55 minutes; Drug: THC-Low Dose; 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes
Active Comparator: 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes; Low dose DMT	Drug: DMT-Low Dose; 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes
Active Comparator: 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.; Medium Dose DMT	Drug: DMT-Medium Dose; 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.
Active Comparator: 0.5 mg over 5 minutes and then 2 mg over and 55 minutes; THC-Medium Dose	Drug: THC-Medium Dose; 0.5 mg over 5 minutes and then 2 mg over and 55 minutes
Active Comparator: 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes; Low Dose THC	Drug: THC-Low Dose; 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Physiological indices	Pulse oximetry will be measured continuously.	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	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	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.	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.	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	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.	Test Day Time points (Minutes): +120
Electrophysiological		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].
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).	Test Day Time points (Minutes): -60, +30, +120, 180 (end of test day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expectancy Effects		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.	Time Frame: 0; immediately after DMT administration, and +180 minutes at the end of the study
Blood		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: -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	Time Frame: +180 minutes after DMT administration

Collaborators and Investigators

• Sponsor: Deepak C. D'Souza
• Investigators: Principal Investigator: Deepak D'Souza, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 2000034770

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No