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

Phase 1RecruitingNCT06671977

Deepak C. D'Souza60 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Enrollment

Conditions

Major Depression Disorder Depression

Interventions

Eligibility

Sex: ALLMin age: 21 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Safety of Physiological indices

Pulse oximetry will be measured continuously.

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.

Psychedelic Effects

The 30-item revised Mystical Experience Questionnaire (MEQ30) will be used to measure mystical/psychedelic experiences associated with drugs like psilocybin

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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).

Time frame: Test Day Time points (Minutes): -60, +30, +120, 180 (end of test day)

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].

Secondary Outcomes

Expectancy Effects

Time frame: 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: 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

The Acceptance and Action Questionnaire (AAQ) is a one-factor, likert scale assessment of psychological inflexibility

Time frame: Time Frame: +180 minutes after DMT administration