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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effects of DMT, a psychedelic compound, on individuals with depression and healthy participants. Researchers aim to determine if DMT can reduce depression symptoms and cause brain changes, measured in both groups. Participants will receive varying doses of DMT or a placebo for comparison. The study seeks individuals with moderate to severe depression who have not responded to other treatments, as well as healthy individuals without a history of mental health disorders or substance abuse. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking treatment.

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.

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

Research has shown that DMT (dimethyltryptamine) is generally safe and well-tolerated in studies involving both healthy volunteers and individuals with depression. For instance, one study found that inhaling DMT did not cause serious side effects and was manageable for participants. Another study confirmed DMT's safety, noting no serious negative effects. While some participants experienced strong psychedelic effects, these were expected and not harmful.

This trial also examines THC (tetrahydrocannabinol), the main active ingredient in cannabis. Although specific safety data for THC in this trial isn't available yet, THC is already used in other approved treatments.

Participants in past studies have not reported major safety issues with these treatments. However, as this is a Phase 1 trial, the primary focus is on assessing safety, and more detailed information will emerge as the research progresses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for depression because they use DMT and THC, which are quite different from the usual antidepressants like SSRIs or SNRIs. DMT, known for its psychedelic effects, could potentially offer rapid relief by altering serotonin receptors in the brain, leading to fast and profound changes in mood and perception. THC, the active compound in cannabis, might help by interacting with the endocannabinoid system, which influences mood regulation. These treatments are delivered intravenously, allowing for precise dosing and potentially quicker onset of effects compared to traditional oral medications. This novel approach could be a game-changer for those who haven't found relief with existing therapies.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that dimethyltryptamine (DMT) can significantly reduce symptoms of depression. In one study, 85.71% of individuals with treatment-resistant depression experienced improvement, and 57.14% saw their symptoms nearly disappear within a week, with effects lasting up to three months. Another small study found that depression symptoms noticeably decreased just one day after taking DMT. Short DMT sessions are generally safe and can quickly alleviate depression symptoms. While more research is needed, these findings suggest DMT could be a promising treatment for depression. Participants in this trial will receive varying doses of DMT or a placebo to further evaluate its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Deepak D'Souza, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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

I am willing to only take medications approved by the study doctor.

English speaking

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. 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 ...

2. 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 administration. While larger (but ...

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230890

Benefits and Challenges of Ultra-Fast, Short-Acting ... Short interventions (15–30 min) with 5-MeO-DMT and DMT are safe and well tolerated and can induce marked improvement in symptoms of depression within 24 hours.

4. 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 ...

5. 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.

6. 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.