DMT for Depression

(DMT-Bolus Trial)

Overseen By Deepak C D'Souza, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Deepak C. D'Souza

Must not be taking: Antidepressants, 5HT2A agonists, others

Disqualifiers: Psychosis, Suicidal behavior, Substance use, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, if you are currently taking antidepressants or certain other medications, you may need to stop them before participating in the trial. You must be off these medications for at least five half-lives of the medication's major metabolites before the first test session, and this should be done under clinical supervision with your clinician's approval.

What data supports the effectiveness of the drug DMT for depression?

In a small exploratory study, intravenous DMT showed potential rapid antidepressant effects in patients with treatment-resistant major depressive disorder, as their depression scores decreased significantly the day after receiving the drug. ^{1 2 3 4 5}

How does the drug DMT differ from other treatments for depression?

DMT (dimethyltryptamine) is unique because it is a potent psychedelic drug that acts rapidly and is short-acting, with potential next-day antidepressant effects when administered intravenously. Unlike traditional antidepressants, DMT's effects are experienced quickly, and it is being explored for its use in treatment-resistant depression. ^{1 2 6 7 8}

Research Team

Deepak D'Souza, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for individuals with depression, including major depression. It's also open to healthy people as a control group. Participants must meet specific health requirements and be willing to undergo EEG measures and mood assessments.

Inclusion Criteria

Body mass index between 18-35 kg/m2

English speaking

Able to provide informed consent

Exclusion Criteria

Living outside the US

I haven't had cancer, except for skin cancer, in the last 5 years.

Recent clinically significant aggressive behavior

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DMT or THC at varying doses, with physiological and psychological effects monitored throughout the test day

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of anxiety, depression, and other psychological effects

1-2 weeks

Treatment Details

Interventions

• DMT

Trial Overview The study tests the effects of two doses each of DMT and THC on depression symptoms and brain changes. Researchers will use EEG to track neuroplasticity and psychometric tools to measure mood alterations in participants.

Participant Groups

Group I: 10 mg slow intravenous push (bolus) over 5 minutes and then 0.01 mg/kg/min for 55 minutes Active Control 1 Intervention

Low dose DMT

Group II: 14 mg slow intravenous push (bolus) over 5 minutes and then 0.015 mg/kg/min for 55 minutes. Active Control 1 Intervention

Medium Dose DMT

Group III: 0.5 mg over 5 minutes and then 2 mg over and 55 minutes Active Control 1 Intervention

THC-Medium Dose

Group IV: 0.1 mg slow intravenous push (bolus) over 5 minutes and then I mg over 55 minutes Active Control 1 Intervention

Low Dose THC

Group V: Placebo Placebo Group 4 Interventions

Who Is Running the Clinical Trial?

Deepak C. D'Souza

Lead Sponsor

Trials

1

Recruited

60+

Findings from Research

The psychedelic drug 5-MeO-DMT (GH001) was well tolerated in a study of 16 adults with treatment-resistant depression (TRD), showing significant safety in its administration.

In the Phase 2 trial, an individualized dosing regimen led to an impressive 87.5% remission rate by day 7, demonstrating potent and ultra-rapid antidepressant effects compared to lower remission rates in the single-dose groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression. Reckweg, JT., van Leeuwen, CJ., Henquet, C., et al.[2023]

In a small exploratory phase 1 study involving 10 participants (7 with major depressive disorder and 3 healthy controls), intravenous DMT was found to be mostly safe and well-tolerated, with no dropouts and only mild adverse events reported.

Participants with treatment-resistant major depressive disorder experienced a significant reduction in depression symptoms the day after receiving a 0.3 mg/kg dose of DMT, indicating potential rapid antidepressant effects that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. D'Souza, DC., Syed, SA., Flynn, LT., et al.[2023]

In a survey of 362 participants who used 5-MeO-DMT in a structured group setting, 80% of those with depression and 79% with anxiety reported improvements in their conditions after use, suggesting potential therapeutic effects.

The improvements in depression and anxiety were linked to the intensity of mystical experiences and the perceived spiritual significance of the 5-MeO-DMT experience, rather than the challenging effects during the experience, indicating a unique mechanism of action that warrants further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Davis, AK., So, S., Lancelotta, R., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The meaningful change threshold as measured by the 16-item quick inventory of depressive symptomatology in adults with treatment-resistant major depressive and bipolar disorder receiving intravenous ketamine. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Ketamine administration in depressive disorders: a systematic review and meta-analysis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Intravenous Racemic Ketamine Infusions in a Large Community Sample of Patients With Treatment-Resistant Depression, Suicidal Ideation, and Generalized Anxiety Symptoms: A Retrospective Chart Review. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Dance Movement Therapy in the Treatment of Adults With Depression: A Systematic Review With Meta-Analyses. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Dance Movement Therapy in the Treatment of Depression: A Multicenter, Randomized Controlled Trial in Finland. [2020]

8. England pubmed.ncbi.nlm.nih.gov

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. [2020]