Papers

Research literature with structured metadata.

Trials

Registered studies by status, phase, and compound.

Topics

Indications and themes psychedelics are researched for.

Compounds

Evidence across molecules with rich data.

Countries

Regulation, access, and research activity by region.

Stakeholders

Organizations shaping the space across research, policy, and funding.

People

Investigators, clinicians, and authors with mapped output.

Courses

Training programs and certifications across modalities.

Events

Conferences, workshops, and convenings by date and focus.

Results

Compare outcome data across trials and publications.

Research Snapshot

One-page overview of trials, participants, papers, and research networks.

Clinical Guidelines

Trial-anchored manuals and protocol guidance with competency mapping.

Research recaps

Monthly evidence summaries with key takeaways.

Map of research

Landscape view of trials, compounds, and outcomes.

Newsletter

Weekly or daily updates on trials, publications, analysis, and more.

Research Groups

Worldwide map of psychedelic research centres by region.

Road to Access

Science, regulation, and economics on the path to patient access.

Research Network

Interactive co-authorship map of psychedelic researchers.

Top papers

Find needles in the haystack of psychedelic research per topic.

AskBeta
Pricing

The intelligence layer for psychedelic research.

Company

  • About
  • Contact
  • Newsletter

Product

  • Feedback
  • Roadmap
  • Changelog
  • API
  • Partners
  • Clinical Guidelines

Legal

  • Privacy
  • Terms

© 2026 Blossom. All rights reserved.

Home/Research/DMT/Major Depressive Disorder (MDD)

DMT for Major Depressive Disorder (MDD)

11 papers and 10 clinical trials exploring dmt as a treatment for major depressive disorder (mdd).

CompoundTryptamine

DMT

A powerful, short-acting tryptamine psychedelic found in many botanical sources, known for rapid onset and intense subjective experiences.

Full DMT profile
IndicationOver 264 million worldwide.

Major Depressive Disorder (MDD)

Major Depressive Disorder (MDD) represents a significant mental health challenge, with emerging research into the efficacy of psychedelics like psilocybin and ketamine offering new avenues for treatment. Recent studies have demonstrated the potential of these compounds to alleviate symptoms, particularly in treatment-resistant cases of MDD.

Full Major Depressive Disorder (MDD) profile

Academic Research

11 papers
Open Accessindividual

A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer

In a randomized, placebo‑controlled ascending‑dose study in 48 healthy volunteers, single IV doses of GM‑2505 up to 20 mg were well tolerated and showed dose‑proportional pharmacokinetics (t1/2 40–50 min) with dose‑dependent neuroendocrine, neurophysiological and subjective psychedelic effects, including decreased theta/alpha and increased gamma EEG power. The duration of cardiovascular and subjective effects was intermediate between psilocybin and DMT, indicating a practical 10–15 mg IV dose range for supervised clinical use.

Published
October 16, 2025
Journal
Journal of Psychopharmacology
Authors
Marek, G. J., Makai-Bölöni, S., Umbricht, D., Christian, E. P., Winters, J., Dvorak, D., Raines, S., Hughes, Z. A., Austin, E. W., Klein, A. K., Leong, W., Krol, F. J., Van Der Graaf, A. J., Juachon, M. J., Otto, M. E., Borghans, L. G. J. M., Jacobs, G., Kruegel, A. C., Sporn, J.
Paywallindividual

Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

This rat study found that zalsupindole (third-generation psychedelic) produced robust effects on structural and functional neuroplasticity in the prefrontal cortex as well as sustained antidepressant-like responses comparable to or greater than those of ketamine, psilocybin, and DMT, despite lacking any of the acute cellular and behavioural characteristics of hallucinogenic or dissociative compounds.

Published
October 13, 2025
Journal
ACS Chemical Neuroscience
Authors
Agrawal, R., Gillie, D., Mungenast, A., Chytil, M., Engel, S., Wu, M. C., Rasmussen, K., Salinas, E., Olson, D. E.
Paywallindividual

Safety, tolerability and subjective effects of vaporized N,N-Dimethyltryptamine: A randomized double-blind clinical trial

This first RCT (n=25) of vaporised DMT (60mg) demonstrated that DMT significantly increased subjective experience measures while causing only transient, safe physiological changes and predominantly mild adverse events. This suggests that inhaled DMT is safe, well-tolerated, and effective at inducing profound altered states of consciousness. Significant correlations were observed between physiological responses and subjective experiences.

Published
June 17, 2025
Journal
European Neuropsychopharmacology
Authors
Wießner, I., Falchi-Carvalho, M., Laborde, S., Barros, H., Bolcont, R., Ruschi Silva, S., Pantrigo, E. J., Medina, M., Arichelle, F., Almeida, R., Aires, R., Nunes Ferreira, L. F., Dantas Correa, L., da Costa Bezerra, R. B., Thie, K., Silva-Costa, N., Araújo, D. B., de Araujo Costa Neto, L. A., Lima de Queiroz, M. V. J., Galvão-Coelho, N. L., Palhano-Fontes, F.
Paywallindividual

Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression

This open-label fixed-order dose-escalation trial (n=14) evaluated inhaled DMT (15mg & 60mg) for treatment-resistant depression (TRD) for the first time. Results showed rapid and sustained antidepressant effects with a 21-point reduction on the Montgomery-Asberg Depression Rating Scale by day 7 (p<0.001), an 86% response rate, and a 57% remission rate lasting up to 3 months, with significant decreases in suicidal ideation (SI).

Published
April 22, 2025
Journal
Neuropsychopharmacology
Authors
Falchi-Carvalho, M., Palhano-Fontes, F., Wießner, I., Barros, H., Bolcont, R., Laborde, S., Silva, S. R. B., Montanini, D., Barbosa, D. C., Teixeira, E., Florence-Vilela, R., Almeida, R., Macedo, R. K. A., Arichelle, F., Pantrigo, E. J., Costa-Macedo, J. V., da Cruz Nunes, J. A., Araújo, D. B., de Araujo Costa Neto, L. A., Nunes Ferreira, L. F., Dantas Correa, L., da Costa Bezerra, R. B., Arcoverde, E., Galvão-Coelho, N. L.
Open Accessmeta

A review of psychedelics trials completed in depression, informed by European regulatory perspectives

This systematic review (s=8) analyses completed controlled trials of psychedelics for depression, including psilocybin, LSD, ayahuasca, and DMT, all in Phase II or I/II. It evaluates methodological patterns against the draft European Medicines Agency guideline revision, highlighting challenges such as unblinding, expectancy, and adverse event characterisation, while calling for larger studies to assess long-term efficacy and safety.

Published
January 1, 2025
Journal
Neuroscience Applied
Authors
Silva, F., Butlen-Ducuing, F., Guizzaro, L., Balabanov, P., Meyer-Lindenberg, A.
Open Accessindividual

Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial

In a randomized, placebo‑controlled Phase 1 trial in psychedelic‑naïve healthy volunteers, single escalating IV doses of SPL026 (DMT fumarate) were well tolerated with an acceptable safety profile and showed dose‑related increases in acute psychometric intensity that correlated with plasma concentrations; based on safety, PK and pharmacodynamic data a 21.5 mg two‑phase 10‑minute infusion was selected for the subsequent Phase 2a study.

Published
January 11, 2024
Journal
Frontiers in Psychiatry
Authors
James, E., Erritzoe, D., Benway, T., Joel, Z., Timmermann, C., Good, M., Agnorelli, C., Weiss, B., Barba, T., Campbell, G., Jones, M., Hughes, C., Topping, H., Boyce, M., Routledge, C.

Clinical Trials

10 trials
RecruitingPhase II

Inhaled DMT for Major Depressive Disorder

This Phase IIb, randomised, double-blind, active-controlled trial (n=140) will evaluate the efficacy and safety of inhaled DMT in adults with major depressive disorder (MDD). It will assess whether a higher-dose inhaled DMT regimen can more rapidly reduce depressive symptoms and suicide risk than a lower-dose active comparator, with primary outcomes focused on change in Montgomery-Åsberg Depression Rating Scale (MADRS) score and incidence of suicidal ideation and behaviour. Participants will be allocated 1:1 to receive either 15 mg followed 1 hour later by 60 mg of inhaled DMT, or 1 mg followed 1 hour later by 4 mg, administered via a Volcano Medic 2 vaporiser in two inhalations. Those who do not achieve remission at Day 7 (MADRS >10) will enter an open-label extension and receive a high-dose session on Day 14 (±3 days), while remitters will not be re-dosed; all participants will then be followed for up to 12 months to examine durability of response, safety, functioning and quality of life.

Started
August 1, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07562191
RecruitingPhase NA

Antidepressant Response of DMT Masked With Propofol (DMT4D)

This randomised, placebo-controlled, quadruple-masked trial (n=112) will investigate whether the antidepressant effects of DMT (2 mg/min over 20 minutes; total ~40 mg) in patients with MDD depend on the subjective psychedelic experience by comparing DMT vs placebo under propofol sedation or no sedation.

Started
April 1, 2025
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06927076
RecruitingPhase I

Study of the Safety, Tolerability, Electrophysiological Effects and Efficacy of DMT in Humans (DMT-Bolus)

This Phase I, randomised, placebo-controlled, triple-masked, crossover design trial (n=60) will investigate the safety, tolerability, electrophysiological effects, and efficacy of dimethyltryptamine (DMT) in individuals with major depressive disorder (MDD) and healthy controls.

Started
March 1, 2025
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06671977
CompletedPhase II

Safety, Tolerability and Antidepressant Effects of DMT in Patients With Depression

Open-label Phase II single-group study (n=14) assessing ascending inhaled DMT (15 mg then 60 mg on a single day) for patients with partial response in depression.

Started
October 9, 2023
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT06094907
CompletedPhase I

IM and IV SPL026 Drug Product in Healthy Participants

Open-label, crossover study (n=14) assessing IM and IV SPL026 (DMT) in healthy participants with varying psychedelic experience (Part A crossover IM→IV; Part B single IM).

Started
January 3, 2023
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT05644093
CompletedPhase I

Safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of intravenous dosing of SPL026 drug product (N, N-dimethyltryptamine fumarate; DMT Fumarate [A Serotonergic Psychedelic]) alone or in combination with selective serotonin reuptake inhibitors in patients with major depressive disorder

Open-label Phase I study (n=24 planned; 18 enrolled) single 27.5 mg IV SPL026 (DMT fumarate) 10-minute infusion in adults with major depressive disorder, comparing patients on stable SSRI versus those not on pharmacotherapy; primary outcomes: safety, PK/PD and exploratory efficacy.

Started
December 13, 2022
Type
interventional
Blinding
none
Randomized
No
Registry ID
ISRCTN10974027

Explore further

Search all DMT papers Search all Major Depressive Disorder (MDD) trials Full DMT profile Full Major Depressive Disorder (MDD) profile