DMT for Depression

Overseen By Leigh T Flynn, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Disqualifiers: Unstable medical conditions, Psychiatric illness

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of dimethyltryptamine (DMT) for treating depression. DMT is a compound that may improve mood and mental health. Participants will receive varying doses of DMT through an IV to assess its impact on their depression. The study seeks medically healthy individuals diagnosed with major depressive disorder, as well as healthy individuals without depression for comparison. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that DMT (dimethyltryptamine) is generally safe for humans. In past studies, participants reported no serious side effects. They found DMT manageable, though it did produce strong effects, such as altered perception and a sense of losing self-identity.

Other studies have shown similar results when DMT was inhaled. Participants tolerated it well and experienced changes in their state of mind. This indicates that DMT can cause profound changes in awareness and perception.

This trial is in its early stages, focusing on safety. Participants will be closely monitored. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for depression, which typically include SSRIs like Prozac and Zoloft, DMT offers a unique approach. Researchers are excited about DMT because it acts on serotonin receptors in the brain in a different way, potentially leading to rapid antidepressant effects. Additionally, DMT is administered intravenously, which could allow for more controlled dosage and faster onset of action compared to oral medications. This novel mechanism and delivery method offer hope for quicker relief of depressive symptoms.

What evidence suggests that dimethyltryptamine (DMT) might be an effective treatment for depression?

Research has shown that DMT may help reduce depression symptoms. In a small study, participants felt significantly less depressed just one day after taking DMT. Other studies have found that depression improved notably 1-2 weeks after taking DMT, with some benefits lasting up to 3 months. In another trial, 85.71% of participants had a positive response, and 57.14% no longer showed signs of depression 7 days after taking DMT. Overall, these findings suggest DMT could be effective in treating depression. This trial will compare two different dosages of DMT, 0.1 mg/kg and 0.3 mg/kg, to evaluate their effectiveness in reducing depression symptoms. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people who are mentally and physically healthy, without any major depressive disorder or other psychiatric conditions. It's designed to see if DMT can be safe and effective for those not currently experiencing depression.

Inclusion Criteria

People who are in good health and not participating as patients.

I am in good health.

You have no psychiatric disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Participants receive escalating doses of DMT administered intravenously to assess safety and efficacy

1 day per dose level

Multiple visits for each dose level

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dimethyltryptamine (DMT)

Trial Overview The study is testing two different doses of Dimethyltryptamine (DMT), a psychedelic compound: one lower dose at 0.1 mg/kg and a higher dose at 0.3 mg/kg, to understand its effects on humans in a controlled setting.

How Is the Trial Designed?

Group I: 0.1 mg/kg DMT Active Control 1 Intervention

0.1 mg/kg DMT administered intravenously

Group II: 0.3 mg/kg DMT Active Control 1 Intervention

0.3 mg/kg DMT administered intravenously

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

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]

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 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]

Citations

1. nature.com nature.com/articles/s41598-024-53363-y

Effects of DMT on mental health outcomes in healthy ... Within a very small sample (n = 6), one recent study found significant decreases in depression 1 day after DMT administration28.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38326357/

Effects of DMT on mental health outcomes in healthy ... In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40258990/

a phase 2a clinical trial in treatment-resistant depression The response rate was 85.71%, and the remission rate was 57.14% 7 days post-administration, lasting up to 3 months. Suicidal ideation ...

4. med.uth.edu med.uth.edu/psychiatry/2025/05/07/vaporized-dmt-shows-promise-for-rapid-and-sustained-relief-in-treatment-resistant-depression/

Vaporized DMT Shows Promise for Rapid and Sustained ... 71% responded to treatment (≥50% reduction in depression scores) by day 7. · 14% achieved remission (minimal depressive symptoms) by day 7.

5. biorxiv.org biorxiv.org/content/10.1101/2025.04.26.650765v1.full-text

Single-dose DMT reverses anhedonia and cognitive ... DMT administered after UCMS reversed depressive-like behavior and restored cognitive performance, outperforming chronic fluoxetine across most ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40484114/

Safety and tolerability of NN-dimethyltryptamine (DMT) in ... No serious adverse events were reported, and DMT was generally well-tolerated. Psychotomimetic effects, including ego dissolution and mystical ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X25001129

Safety, tolerability and subjective effects of vaporized N,N ... Our findings suggest that inhaled DMT is safe, well-tolerated, and capable of inducing profound altered states of consciousness.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06094907?term=DIMETHYLTRYPTAMINE&rank=4

Safety, Tolerability and Antidepressant Effects of DMT in ... This study aims to evaluate the acute and subacute effects of an inhaled N, N- Dimethyltryptamine (DMT) in patients with partial response in depression.