Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans

NCT06671977 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2000034770
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (9)

• 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

• 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)

• 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].

Secondary Outcomes (5)

• Expectancy Effects

  Subjects will be tested for expectancy effects at screening, and before each dosing session.

• Adequacy of blinding

  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

  Time Frame: +180 minutes after DMT administration

Study Arms (5)

10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes

ACTIVE COMPARATOR

Low dose DMT

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

Drug: DMT-Medium Dose

0.5 mg over 5 minutes and then 2 mg over and 55 minutes

ACTIVE COMPARATOR

THC-Medium Dose

Drug: THC-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

Low Dose THC

Drug: THC-Low Dose

Interventions

DMT-Medium Dose DRUG

14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.

14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.; Placebo

DMT-Low Dose DRUG

10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes

10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes; Placebo

THC-Medium Dose DRUG

0.5 mg over 5 minutes and then 2 mg over and 55 minutes

0.5 mg over 5 minutes and then 2 mg over and 55 minutes; Placebo

THC-Low Dose DRUG

0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes

0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes; Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females
• Age 21 to 65 years;
• Body mass index between 18-35 kg/m2;
• English speaking
• Able to provide informed consent;
• Willing to refrain from taking any medications not approved by the study physician;
• Willing to refrain from using street drugs and alcohol the day before, the day of, and the day after each test session;
• Negative urine drug screen on the morning of each test session (the following drugs will be tested for: cocaine, opioids, benzodiazepines, cannabinoids, stimulants);
• 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.
• Diagnosed with Major Depressive Disorder (MDD), single or recurrent episode, and currently experiencing a Major Depressive Episode (MDE), of a moderate to severe degree (Score ≥17 on the 21-item clinician-rated HAMD);
• Unsatisfactory response to at least one adequate antidepressant trial (at least 6 weeks on a therapeutic dose) during the current depressive episode and/or unable to tolerate existing antidepressants, assessed with the Antidepressant Treatment History Form - Short Form (ATHF-SF) and confirmed with the primary mental health provider (see clinician contact form);
• Engaged in treatment for depression with a clinician and willing to continue treatment for the duration of the study;
• Those not engaged in treatment t the time of screening will be required to engage in treatment as a condition of study participation.

You may not qualify if:

• Recent clinically significant current risk for suicidal behavior as assessed by chart review, opinion of mental health provider and Columbia Suicide Rating Scale (CSSRS);
• Recent clinically significant aggressive behavior assessed by chart review, opinion of mental health provider and psychiatric screening;
• Psychosis:
• Current or past history of any psychotic disorder including Schizophrenia, Bipolar I Disorder, Delusional Disorder, Paranoid Personality Disorder, or Schizoaffective Disorder (clinical judgement will be exercised);
• History of psychotic symptoms in the current or previous depressive episodes;
• Currently taking an antidepressant medication (including SSRIs, SNRIs, TCAs, and MAOIs) or other medications (e.g., efavirenz, locanserin) that may alter the effects of 5HT2A agonists. Exceptions are medications used at low doses for sleep. If a subject meets all other study criteria, he/she may consider discontinuation of antidepressant under clinical supervision contingent upon the approval of the patient's clinician. Subjects will need to be off prohibited medications for at least five half-lives of the medication's major metabolites prior to the first test session;
• Currently taking over the counter products such as 5-hydroxytryptophan and St. John's wort, due to potential interactions with DMT;
• Cognitive dysfunction that could interfere with study participation;
• Recent history of meeting criteria for alcohol or substance use disorder (excluding caffeine and nicotine);
• Alcohol use of ≥7 drinks in females and 14 in males per week (NIAAA guidelines);
• Any lifetime history of hallucinogen use disorder;
• Regular (≥once per month) use or misuse of serotonergic hallucinogens including DMT, psilocybin, LSD, and related compounds;
• History of intolerance to drugs known to significantly alter perception, e.g., DMT, THC ketamine, psilocybin, LSD, Salvinorin A, mescaline, etc.;
• Hypotension, as defined as a baseline blood pressure \< 90/60 mmHg or orthostatic hypotension as defined as a sustained reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of 10 mm Hg within 3 min of standing or head-up tilt;
• Pregnancy or currently breast feeding (lactation);

Sponsors & Collaborators

• Deepak C. D'Souza: lead

Study Sites (1)

Biological Studies Unit at the VA Connecticut Healthcare System, Yale School of Medicine,

West Haven, Connecticut, 06516, United States

RECRUITING

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Deepak D'Souza, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deepak C D'Souza, MD

CONTACT

(203) 932-5711; deepak.dsouza@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deepak Cyril D'Souza, MD

Model Details: 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

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: November 4, 2024
• Study Start: March 14, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 2, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)