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DMT for depression

Studies whose primary subject is both DMT and Depression, with an evidence synthesis read across the most-cited and most recent of them.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for DMT, dimethyltryptamine, N,N-DMT, Depression, major depressive disorder, MDD, then ranked by relevance.

The research on DMT for depression is early-stage but points in a positive direction: small open-label trials of inhaled or intravenous DMT and 5-MeO-DMT report rapid reductions in depression scores, with response and remission rates often high and some effects lasting weeks to months. Animal studies generally support rapid, long-lasting antidepressant-like effects, and reviews describe the evidence as promising but limited. The main caveats are very small samples, mostly open-label or uncontrolled designs, scarce long-term durability data, and a lack of rigorous placebo-controlled trials.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Study Design Sample size Direction Finding
Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression 2018 experimental study Supports DMT produced antidepressant- and anxiolytic-like behavioral effects in rats, including reduced immobility in the forced swim test and facilitated extinction of cued fear memory.
Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. 2022 open-label dose-escalation phase 1 study 10 Supports Intravenous DMT at 0.3 mg/kg was associated with a significant next-day reduction in HAMD-17 depression scores in treatment-resistant MDD patients.
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. 2019 cross-sectional survey 362 Supports Most respondents with prior depression or anxiety diagnoses reported improvement after 5-MeO-DMT use, with greater improvement associated with mystical experience intensity and spiritual significance.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders. 2021 review 70 Unclear As of December 2020, 70 registered trials were investigating psychedelics for psychiatric disorders, with DMT and 5-MeO-DMT among the less common compounds studied for MDD and only 21 studies having published results.
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 phase 1/2 clinical trial 16 Supports An individualized dosing regimen of inhaled 5-MeO-DMT produced an 87.5% remission rate at day 7 in treatment-resistant depression, outperforming single-dose administration.
Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression. 2025 open-label trial 14 Supports Inhaled DMT produced rapid and sustained antidepressant effects, with an average 21.14-point reduction on the MADRS by day 7 and high response and remission rates.
Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. 2024 double-blind placebo-controlled single ascending dose study 44 Supports Intranasal 5-MeO-DMT was well tolerated up to 12 mg with dose-proportional exposure and dose-related mystical-type effects, but the study assessed safety and pharmacodynamics rather than depression outcomes.
Role of Psychedelics in Treatment-Resistant Depression. 2023 review Mixed Evidence for classic psychedelics including ayahuasca/DMT in treatment-resistant depression is limited, though early studies show promising results, and the field may be subject to a hype bubble.
Psilocybin and Other Classic Psychedelics in Depression. 2024 review Supports Psychedelics targeting the 5-HT2A receptor, including DMT, can produce rapid mood improvement in depressed individuals that can last for months when coupled with psychological support.
Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review 2021 systematic review 10 Supports Most included studies showed a significant correlation between psilocybin and DMT use and reduction in depression symptom intensity, but further observations were deemed necessary.
Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression 2025 review Supports Early clinical trials in small samples show that short 5-MeO-DMT and DMT interventions are safe and can induce marked improvement in depression symptoms within 24 hours that sustains for at least one week, though long-term efficacy data are scarce.
Ayahuasca for the Treatment of Depression. 2022 review Supports Open and randomized placebo-controlled trials of ayahuasca, which contains DMT, show significant and rapid antidepressant effects starting as early as one day after intervention.
A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT) 2017 case study 1 Opposes Chronic self-administration of DMT augmented with phenelzine in a physician with bipolar depression resulted in mania and psychosis.
The current state of ayahuasca research in animal models: A systematic review. 2023 systematic review 32 Supports Animal studies indicate ayahuasca is safe at ceremonial-comparable doses and shows an antidepressant effect, while anxiety-related outcomes remain inconclusive.
The Antidepressant Effects of Vaporized N,N-Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant Depression. 2025 open-label clinical trial 6 Supports Vaporized DMT produced rapid and sustained antidepressant effects, with 83.33% of patients responding by day 7 and 66.67% maintaining response at one month.
Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression 2026 open-label clinical trial 41 Supports Inhaled DMT with psychological support was associated with reduced anxiety, increased life satisfaction, and sustained improvements in quality of life in patients with treatment-resistant depression.
N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. 2026 animal study Supports DMT was as effective as S-ketamine in producing rapid and long-lasting antidepressant-like effects in helpless mice and also showed anxiolytic-like effects.
Treatment of major depressive disorder and treatment resistant depression with 5-MeO-DMT: Impact of 25 years of non-traditional public scientific communication and education on clinical development and commercialization 2026 review Supports Informal and underground use of 5-MeO-DMT has generated substantial knowledge about alleviating depressive symptoms, but communication gaps hinder its integration into mainstream psychiatry.
Ayahuasca Therapy: Possible Reduction of Suicidal Ideation in Treatment-Resistant Depression - A Systematic Review. 2026 systematic review 5 Supports Ayahuasca administration was consistently associated with rapid and significant reductions in suicidal ideation and depressive symptoms in patients with depressive disorders.
Intranasal 5-MeO-DMT Concomitant with SSRI for Treatment-Resistant Depression: A Proof-of-Concept Trial. 2026 proof-of-concept trial Supports Intranasal 5-MeO-DMT combined with an SSRI was well tolerated and showed preliminary antidepressant effects in treatment-resistant depression.
A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression 2026 phase 2 open-label clinical trial Supports A single dose of intranasal BPL-003 produced a rapid and sustained reduction in MADRS score over 12 weeks in people with treatment-resistant depression.
Vaporizable Formulation of 5-MeO-DMT and THCV as Prophylactic or Therapeutic Agent for Treatment-Resistant Depression (TRD) and Anxiety Disorders 2026 theoretical paper Unclear Argues that co-administering 5-MeO-DMT and THCV via a precision vaporization device may provide a more effective and tolerable treatment for treatment-resistant depression and anxiety disorders.
5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines. 2026 preclinical animal study 11 No effect Intranasal 5-MeO-DMT did not induce seizures or epileptiform activity in a canine model, addressing seizure liability rather than antidepressant efficacy.
Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model. 2026 preclinical animal study Supports A single dose of DMT reversed depressive-like behavior and cognitive deficits in stressed male mice and enhanced adult-born granule cell integration, outperforming fluoxetine in most domains.
Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study. 2025 randomized controlled trial Supports Sub-psychedelic sublingual doses of 5-MeO-DMT were safe and well tolerated with dose-dependent brain modulation, but the study assessed safety and tolerability rather than antidepressant efficacy.

Points of agreement

  • Small open-label clinical trials of DMT and 5-MeO-DMT consistently report rapid reductions in depression severity, often within a day and sometimes sustained for weeks to months.
  • Animal studies across multiple models show DMT produces rapid and long-lasting antidepressant-like behavioral effects.
  • Reviews and systematic reviews describe the clinical evidence as promising but limited, with calls for larger controlled trials.
  • Short-acting DMT and 5-MeO-DMT interventions are generally reported as safe and well tolerated in the studied samples.

Conflicts

  • One case study reports mania and psychosis from chronic self-administered DMT with phenelzine, contrasting with the generally positive safety profile in controlled settings.
  • Some reviews caution about a hype bubble and limited evidence, while individual trials report high response and remission rates.

Gaps

  • Lack of large randomized placebo-controlled trials for DMT and 5-MeO-DMT in depression.
  • Limited long-term durability data beyond 12 weeks to 12 months.
  • Most clinical trials are open-label with very small samples, limiting generalizability.
  • Unclear optimal dosing, route of administration, and whether psychological support is necessary.
  • Little research in diverse populations and in depression subtypes other than treatment-resistant depression.
Browse these studies in the library

Common questions

What does the research agree on about DMT for depression?
  • Small open-label clinical trials of DMT and 5-MeO-DMT consistently report rapid reductions in depression severity, often within a day and sometimes sustained for weeks to months.
  • Animal studies across multiple models show DMT produces rapid and long-lasting antidepressant-like behavioral effects.
  • Reviews and systematic reviews describe the clinical evidence as promising but limited, with calls for larger controlled trials.
  • Short-acting DMT and 5-MeO-DMT interventions are generally reported as safe and well tolerated in the studied samples.
Where do studies on DMT for depression conflict?
  • One case study reports mania and psychosis from chronic self-administered DMT with phenelzine, contrasting with the generally positive safety profile in controlled settings.
  • Some reviews caution about a hype bubble and limited evidence, while individual trials report high response and remission rates.
What is still unknown about DMT for depression?
  • Lack of large randomized placebo-controlled trials for DMT and 5-MeO-DMT in depression.
  • Limited long-term durability data beyond 12 weeks to 12 months.
  • Most clinical trials are open-label with very small samples, limiting generalizability.
  • Unclear optimal dosing, route of administration, and whether psychological support is necessary.
  • Little research in diverse populations and in depression subtypes other than treatment-resistant depression.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is DMT for depression, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when DMT for depression or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

The full method, including what a person does and does not review, is on the methods page.

Ask your own question in the Research Synthesis Tool

37 articles · 18 from the last two years · 843 participants across 17 studies reporting sample size

Common study designs

review 9 case study 2 systematic review 4 randomized controlled trial 2 theoretical or philosophical paper 2

Research volume by year

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37 studies whose primary subject is DMT for depression since 2017

Studies about DMT for depression per year, 2017 to 2026, peaking at 9 in 2025 Bar chart: one bar per year, taller where more studies were published that year. 0 5 10 2020 2025
2026 is partial
Show the numbers
Studies about DMT for depression per year, 2017 to 2026, peaking at 9 in 2025
Year Studies
2017 1
2018 1
2019 1
2020 0
2021 3
2022 2
2023 8
2024 3
2025 9
2026 9

Research

Synthesize the evidence →

Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression

Journal of Psychopharmacology July 8, 2026 Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.

BACKGROUND: -dimethyltryptamine (DMT); however, long-term effects, including broader well-being dimensions, are sparsely explored across populations. AIMS: Investigating whether DMT produces sustained improvements in anxiety, life satisfaction, and quality of life, in both healthy individuals and patients with treatment-resistant depression (TRD). METHODS: In 2 open-label clinical trials, 27...

DOI: 10.1177/02698811261465005 (opens in new tab) Anxiety Life satisfaction Depression economics Optimism +8

N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine.

Neuropharmacology July 1, 2026 Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al. 1 citation

N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...

DOI: 10.1016/j.neuropharm.2026.110947 (opens in new tab) Full text (opens in new tab) Anxiety Depression Animal models Mouse +2

Treatment of major depressive disorder and treatment resistant depression with 5-MeO-DMT: Impact of 25 years of non-traditional public scientific communication and education on clinical development and commercialization

Psychedelics April 25, 2026 Juliet Meccia, David Casimir, Sisi Li et al.

Over the past 25 years, the use of 5-MeO-DMT in informal and underground settings has contributed a substantial, yet underrecognized, body of knowledge relating to the efficacy of 5-MeO-DMT in alleviating depressive symptoms. Traditional models of drug development, typically characterized by structured trials and regulatory milestones, rarely consider findings from these alternative routes. The...

DOI: 10.1016/j.psyche.2026.100019 (opens in new tab) Major depressive disorder Mainstream Commercialization Grassroots +8

Ayahuasca Therapy: Possible Reduction of Suicidal Ideation in Treatment-Resistant Depression - A Systematic Review.

Journal of Psychoactive Drugs April 23, 2026 Brayan Jonas Mano-Sousa, Maria Clara Gama Fontes, Ana Clara Anacleto Gonçalves et al.

Suicide, particularly in treatment-resistant depression (TRD), remains a pressing global health issue, with over 700,000 annual deaths. Existing treatments often have limited efficacy and delayed onset, creating a need for rapid-acting interventions. Ayahuasca, a traditional Amazonian psychedelic, has shown potential for rapidly reducing suicidal ideation. Our systematic review evaluated the...

DOI: 10.1080/02791072.2026.2661580 (opens in new tab) Full text (opens in new tab) DMT Ayahuasca Neuroplasticity Psychedelic therapy +2

A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression

Journal of Psychopharmacology February 27, 2026 Claire T. Roberts, Mathieu Seynaeve, Anna O. Ermakova et al.

Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, suggesting BPL-003 could be beneficial in TRD, warranting investigation in larger controlled trials.

DOI: 10.1177/02698811261420087 (opens in new tab) Treatment-resistant depression Major depressive disorder Depression economics Nasal administration +5

Vaporizable Formulation of 5-MeO-DMT and THCV as Prophylactic or Therapeutic Agent for Treatment-Resistant Depression (TRD) and Anxiety Disorders

Preprints.org February 9, 2026 Philippe Henry preprint

The global burden of mental health conditions, including Treatment-Resistant Depression (TRD) and chronic anxiety, has increased. Existing treatments like SSRIs, SNRIs, and TCAs often require weeks for efficacy and do not address synaptic atrophy or the rapid "reset" of the Default Mode Network (DMN) required for immediate relief. While 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) shows rapid...

DOI: 10.20944/preprints202602.0590.v1 (opens in new tab) Panic disorder Neuroplasticity Anxiety disorder Antidepressant +3

5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines.

International journal of toxicology January 31, 2026 Amir Lotfi, Samantha Sparapani, Mylène Pouliot et al.

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and other psychiatric disorders. A critical safety concern for serotonergic compounds is their potential to induce seizures, as a severe manifestation of serotonin toxicity. The objective of this study was to evaluate the seizure liability of 5-MeO-DMT in a...

DOI: 10.1177/10915818261419429 (opens in new tab) Full text (opens in new tab) Depression Serotonin Cns safety pharmacology EEG +3

Single-dose DMT reverses anhedonia and cognitive deficits via restoration of neurogenesis in a stress-induced depression model.

Translational Psychiatry January 29, 2026 Rafael V Lima Da Cruz, Rêmullo B. G. De Miranda Costa, Gabriel M. De Queiroz et al. 2 citations

Major depressive disorder (MDD) remains a leading cause of disability worldwide, with current treatments limited by delayed onset and low efficacy. The serotonergic psychedelic N,N-dimethyltryptamine (DMT) has shown rapid antidepressant effects in early clinical studies, yet its mechanisms and efficacy remain poorly characterized in established models of depression. Here, we evaluated the...

DOI: 10.1038/s41398-026-03852-7 (opens in new tab) Full text (opens in new tab)

Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 15, 2025 Maria Beatriz Bistue Millón, Laura Noguera, Diana Bruno et al. 4 citations

This Phase I clinical trial is the first to rigorously evaluate the safety, tolerability, and pharmacokinetics of a novel sublingual formulation of 5-MeO-DMT, administered at sub-psychedelic doses to adults with moderate to high levels of anxiety and/or depression, without formal psychiatric diagnosis or ongoing treatment. Using a double-blind, placebo-controlled design, participants received a...

DOI: 10.1038/s41386-025-02167-3 (opens in new tab) Full text (opens in new tab) 5-MEO-DMT Mental health therapy Clinical trials Drug safety

Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy.

ACS Medicinal Chemistry Letters June 12, 2025 Robert B. Kargbo 1 citation

Innovative formulations of N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enable parenteral and intranasal delivery, respectively. These delivery systems overcome limitations of poor bioavailability and rapid metabolism, offering rapid-onset, short-duration therapeutic effects. The compositions support controlled psychedelic interventions for psychiatric...

DOI: 10.1021/acsmedchemlett.5c00265 (opens in new tab) Full text (opens in new tab) 5-MEO-DMT Treatment-resistant depression Entheogenic treatment Hallucinogen-assisted therapy +9

Clinical trials

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