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Home/Research/Ayahuasca/Treatment-Resistant Depression (TRD)

Ayahuasca for Treatment-Resistant Depression (TRD)

21 papers and 1 clinical trial exploring ayahuasca as a treatment for treatment-resistant depression (trd).

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
IndicationAffects roughly a third of people with depression

Treatment-Resistant Depression (TRD)

Treatment-resistant depression, depression that has not responded to at least two adequate antidepressant trials, is where psychedelic and rapid-acting therapies are furthest along. Esketamine is FDA-approved, and in 2025 a synthetic psilocybin became the first classic psychedelic to meet a Phase 3 endpoint for depression. The progress is real, but so are the caveats: modest effect sizes, short-lived benefits, and unresolved questions about how well these trials are blinded.

Full Treatment-Resistant Depression (TRD) profile

Academic Research

21 papers
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 Accessindividual

The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression

This Phase 2a open‑label, dose‑escalation study in six patients with treatment‑resistant depression found that a single‑day session of vapourised N,N‑dimethyltryptamine produced rapid and sustained reductions in depressive symptoms (mean MADRS change −22 at Day 7 and −17 at one month), with 83.3% response and 66.7% remission at Day 7 and 66.7% response and 50% remission at one month. The authors highlight the non‑invasive, short‑acting delivery as a practical advantage that could improve accessibility of psychedelic-assisted interventional psychiatry.

Published
January 4, 2024
Journal
MedRvix
Authors
Falchi-Carvalho, M., Barros, H., Bolcont, R., Laborde, S., Wießner, I., 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., Arcoverde, E., Galvão-Coelho, N. L., Araújo, D. B., Palhano-Fontes, F.
Open Accessindividual

A quantitative textual analysis of the subjective effects of ayahuasca in naive users with and without depression

Using quantitative textual analysis of open-ended reports from first-time ayahuasca users (9 with treatment-resistant depression, 20 healthy controls), the study identified five core experiential clusters—altered states of consciousness, cognitive changes, somatic alterations, auditory experiences and visual perceptual content—and found that participants with depression reported more aversive bodily reactions. These findings align with central axes of the psychedelic experience and may inform therapeutic applications of ayahuasca.

Published
November 10, 2023
Journal
Scientific Reports
Authors
Cruz, L., Tófoli, L.F., Araújo, D. B., Mograbi, D. C., Favero, B. B.
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.

Clinical Trials

1 trial
CompletedPhase I/II

Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression

This randomised, placebo-controlled parallel trial (n=35) tested a single oral dose of ayahuasca versus placebo in patients with treatment-resistant depression.

Started
February 1, 2014
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT02914769

Explore further

Search all Ayahuasca papers Search all Treatment-Resistant Depression (TRD) trials Full Ayahuasca profile Full Treatment-Resistant Depression (TRD) profile