Depression, Major Depression Disorder
Conditions
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.
Interventions
DRUGDMT-Medium Dose
14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes.
DRUGDMT-Low Dose
10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes
DRUGTHC-Medium Dose
0.5 mg over 5 minutes and then 2 mg over and 55 minutes
DRUGTHC-Low Dose
0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes
Sponsors
Deepak C. D'Souza
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention 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
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Physiological indices | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | The Acceptance and Action Questionnaire (AAQ) is a one-factor, likert scale assessment of psychological inflexibility |
Countries
United States
Contacts
CONTACTDeepak C D'Souza, MD
PRINCIPAL_INVESTIGATORDeepak D'Souza, MD
Yale University
Outcome results
None listed