RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase 1 Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans

Quick Facts

Study Start:2025-03-14

Study Completion:2027-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06671977

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:21 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Males and females 2. Age 21 to 65 years; 3. Body mass index between 18-35 kg/m2; 4. English speaking 5. Able to provide informed consent; 6. Willing to refrain from taking any medications not approved by the study physician; 7. Willing to refrain from using street drugs and alcohol the day before, the day of, and the day after each test session; 8. Negative urine drug screen on the morning of each test session (the following drugs will be tested for: cocaine, opioids, benzodiazepines, cannabinoids, stimulants); 9. Willing and able to abstain from smoking throughout each test session; 10. Women who are of child-bearing potential (WOCBP) and sexually active must be willing to practice an effective means of birth control; 11. Willing not to drive to and from the testing session. 1. 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); 2. 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); 3. Engaged in treatment for depression with a clinician and willing to continue treatment for the duration of the study; 4. Those not engaged in treatment t the time of screening will be required to engage in treatment as a condition of study participation. 5. Consent to allow the research team to engage the primary mental health provider.	1. Recent clinically significant current risk for suicidal behavior as assessed by chart review, opinion of mental health provider and Columbia Suicide Rating Scale (CSSRS); 2. Recent clinically significant aggressive behavior assessed by chart review, opinion of mental health provider and psychiatric screening; 3. Psychosis: 1. 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); 2. History of psychotic symptoms in the current or previous depressive episodes; 4. 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; 5. Currently taking over the counter products such as 5-hydroxytryptophan and St. John's wort, due to potential interactions with DMT; 6. Cognitive dysfunction that could interfere with study participation; 7. Recent history of meeting criteria for alcohol or substance use disorder (excluding caffeine and nicotine); 8. Alcohol use of ≥7 drinks in females and 14 in males per week (NIAAA guidelines); 9. Any lifetime history of hallucinogen use disorder; 10. Regular (≥once per month) use or misuse of serotonergic hallucinogens including DMT, psilocybin, LSD, and related compounds; 11. History of intolerance to drugs known to significantly alter perception, e.g., DMT, THC ketamine, psilocybin, LSD, Salvinorin A, mescaline, etc.; 12. 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; 13. Pregnancy or currently breast feeding (lactation); 14. Medical conditions deemed by the PI (D'Souza), or his designee, to be unstable including but not limited to uncontrolled hypertension (e.g., \>140/90 averaged across four assessments, uncontrolled insulin-dependent diabetes, renal or hepatic failure, seizure disorder, etc.; 15. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation; 16. Any current or past history of any physical condition or abnormal screening laboratory test that, in the investigator's opinion, might put the subject at risk or interfere with study results interpretation. 17. First degree relatives with a history of psychosis 1. Current primary psychiatric disorder other than MDD; 2. Medically significant condition rendering unsuitability for the study; 3. History of mania; 1. No current DSM-V psychiatric disorder, excluding nicotine and caffeine use disorder; 2. No lifetime use of psychiatric medication \>3 months (proxy for psychiatric disorders). 3. No family history of serious mental illness (e.g., schizophrenia, bipolar disorder) 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).

Inclusion Criteria

Exclusion Criteria

1. Males and females
2. Age 21 to 65 years;
3. Body mass index between 18-35 kg/m2;
4. English speaking
5. Able to provide informed consent;
6. Willing to refrain from taking any medications not approved by the study physician;
7. Willing to refrain from using street drugs and alcohol the day before, the day of, and the day after each test session;
8. Negative urine drug screen on the morning of each test session (the following drugs will be tested for: cocaine, opioids, benzodiazepines, cannabinoids, stimulants);
9. Willing and able to abstain from smoking throughout each test session;
10. Women who are of child-bearing potential (WOCBP) and sexually active must be willing to practice an effective means of birth control;
11. Willing not to drive to and from the testing session.
1. 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);
2. 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);
3. Engaged in treatment for depression with a clinician and willing to continue treatment for the duration of the study;
4. Those not engaged in treatment t the time of screening will be required to engage in treatment as a condition of study participation.
5. Consent to allow the research team to engage the primary mental health provider.

1. Recent clinically significant current risk for suicidal behavior as assessed by chart review, opinion of mental health provider and Columbia Suicide Rating Scale (CSSRS);
2. Recent clinically significant aggressive behavior assessed by chart review, opinion of mental health provider and psychiatric screening;
3. Psychosis:
1. 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);
2. History of psychotic symptoms in the current or previous depressive episodes;
4. 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;
5. Currently taking over the counter products such as 5-hydroxytryptophan and St. John's wort, due to potential interactions with DMT;
6. Cognitive dysfunction that could interfere with study participation;
7. Recent history of meeting criteria for alcohol or substance use disorder (excluding caffeine and nicotine);
8. Alcohol use of ≥7 drinks in females and 14 in males per week (NIAAA guidelines);
9. Any lifetime history of hallucinogen use disorder;
10. Regular (≥once per month) use or misuse of serotonergic hallucinogens including DMT, psilocybin, LSD, and related compounds;
11. History of intolerance to drugs known to significantly alter perception, e.g., DMT, THC ketamine, psilocybin, LSD, Salvinorin A, mescaline, etc.;
12. 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;
13. Pregnancy or currently breast feeding (lactation);
14. Medical conditions deemed by the PI (D'Souza), or his designee, to be unstable including but not limited to uncontrolled hypertension (e.g., \>140/90 averaged across four assessments, uncontrolled insulin-dependent diabetes, renal or hepatic failure, seizure disorder, etc.;
15. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation;
16. Any current or past history of any physical condition or abnormal screening laboratory test that, in the investigator's opinion, might put the subject at risk or interfere with study results interpretation.
17. First degree relatives with a history of psychosis
1. Current primary psychiatric disorder other than MDD;
2. Medically significant condition rendering unsuitability for the study;
3. History of mania;
1. No current DSM-V psychiatric disorder, excluding nicotine and caffeine use disorder;
2. No lifetime use of psychiatric medication \>3 months (proxy for psychiatric disorders).
3. No family history of serious mental illness (e.g., schizophrenia, bipolar disorder)
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).

Contacts and Locations

Study Contact

Deepak C D'Souza, MD

CONTACT

(203) 932-5711

deepak.dsouza@yale.edu

Principal Investigator

Deepak D'Souza, MD

PRINCIPAL_INVESTIGATOR

Yale University

Study Locations (Sites)

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

West Haven, Connecticut, 06516

United States

Collaborators and Investigators

Sponsor: Deepak C. D'Souza

Deepak D'Souza, MD, PRINCIPAL_INVESTIGATOR, Yale University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-14

Study Completion Date2027-12-01

Study Record Updates

Study Start Date2025-03-14

Study Completion Date2027-12-01

Terms related to this study

Additional Relevant MeSH Terms

Major Depression Disorder
Depression