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

Ayahuasca for Major Depressive Disorder (MDD)

24 papers and 1 clinical trial exploring ayahuasca as a treatment for major depressive disorder (mdd).

Compoundclassic psychedelic

Ayahuasca

Ayahuasca is a botanical decoction combining DMT with MAO-inhibiting harmala alkaloids, producing intense psychedelic effects lasting 3-6 hours. Clinical trials show rapid, large antidepressant effects from a single dose, with a favourable safety profile in controlled settings.

Full Ayahuasca 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

24 papers
Open Accessmeta

‘Equal-unblinding’ meta-analysis of psychedelic therapy vs. antidepressants for the treatment of depression

In a pre-registered meta-analysis of 8 PAT trials (548 patients) and 16 open‑label traditional antidepressant studies (9,751 patients), psychedelic-assisted therapy was not more effective than open‑label antidepressants on the 17‑item Hamilton Depression Rating Scale (difference 0.3 favouring tAD; 95% CI −1.39 to 1.98; p=0.73). This equal‑unblinding comparison emphasises that blinding integrity materially influences apparent treatment effects and that both PAT and tAD produced robust, clinically meaningful improvements.

Published
June 9, 2025
Journal
OSF Preprints
Authors
Williams, Z. J., Barnett, H., Szigeti, B.
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.
Paywallmeta

Quality of reporting on psychological interventions in psychedelic treatments: a systematic review

This systematic review (s=45) on psychedelic-assisted psychotherapy for mental disorders finds that psychological interventions are reported with low completeness and high heterogeneity. It also finds that MDMA studies are more homogeneous, with greater procedural detail.

Published
December 9, 2024
Journal
Lancet
Authors
Seybert, C., Schimmers, N., Silva, L., Breeksema, J. J., Veraart, J. K. E., Bessa, B. S., d'Orsi, D., Schoevers, R. A., Dinis-Oliveira, R. J.
Open Accessmeta

Effects of psychedelics on neurogenesis: A systematic review of pre-clinical studies

This systematic review of 68 pre-clinical (and related human) studies categorised psychedelics into five classes—CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines and entactogens—and synthesised their reported effects on adult neurogenesis and related brain plasticity. The authors conclude that diverse psychedelic compounds can modulate the birth of new neurons and neural plasticity, supporting further investigation into their therapeutic potential for neuropsychiatric disorders.

Published
July 20, 2023
Journal
Biorxiv
Authors
Lima da Cruz, R. V., Leão, R. N., Moulin, T. C.
Open Accessindividual

Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior

This primate study (n=12) found that ayahuasca (at 3 points in time) led to better resilience to being separated from the family groups. The animals that had received ayahuasca (n=6) showed no indication of anhedonia (inability to feel pleasure) and showed higher cortisol reactivity (positive).

Published
November 4, 2022
Journal
Frontiers in Behavioural Neuroscience
Authors
Galvão-Coelho, N. L., De Meiroz Grilo, M. L. P., de Sousa, G. M., de Sousa, M. B. C., Lobão-Soares, B., Palhano-Fontes, F., de Araujo, D. B., Perkins, D., Hallak, J. E., de Mendoça, L. A. C.

Clinical Trials

1 trial
Unknown statusPhase I

Open-Label Dose-Ranging Study of Oral SM-001 in Healthy Adults

Open-label, Phase I dose-ranging safety study (n=12) in healthy adults testing single oral doses of SM-001 (0.5, 1.0, 2.0 mL/kg) to assess safety and plasma biomarkers.

Started
October 1, 2023
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT05894902

Explore further

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