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Home/Research/Ayahuasca/Depressive Disorders

Ayahuasca for Depressive Disorders

114 papers and 3 clinical trials exploring ayahuasca as a treatment for depressive disorders.

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
IndicationApproximately 260 million people worldwide are affected by depression.

Depressive Disorders

Depressive disorders, particularly major depressive disorder (MDD), are significant contributors to global mental health issues. Research into the therapeutic potential of psychedelics, such as psilocybin and ketamine, offers promising avenues for treatment, especially for cases that are resistant to conventional therapies.

Full Depressive Disorders profile

Academic Research

114 papers
Open Accessindividual

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published
February 18, 2026
Journal
JAMA Psychiatry
Authors
Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.
Open Accessindividual

Naturalistic psychedelic use and changes in depressive symptoms

This longitudinal observational study (n=12,345) of U.S. residents found that naturalistic psychedelic use (n=505, 4.1% of participants) was associated with modest increases in depressive symptoms, particularly when occurring in 'risk contexts' characterised by negative mindset and lack of psychological support, with challenging psychedelic experiences mediating this relationship and suggesting that unsupervised psychedelic use may not be generally therapeutic and could worsen depression under certain circumstances.

Published
December 1, 2025
Journal
Journal of Affective Disorders
Authors
Simonsson, O., Hendricks, P. S., Swords, C. M., Osika, W., Goldberg, S. B.
Open Accessindividual

Intact neurophysiological markers of death denial in long-term ayahuasca users

Using a no‑report MEG visual mismatch response paradigm, the study found that long‑term ayahuasca users report reduced fear of death and greater life satisfaction, but nonetheless retain intact neurophysiological markers of self‑specific death denial at automatic perceptual levels. The neural denial marker correlated with lower self‑reported death acceptance and reduced accessibility of death‑related thoughts, suggesting ayahuasca alters conceptual and affective engagement with death but not unconscious self‑specific denial.

Published
November 10, 2025
Journal
Psychopharmacology
Authors
Dor-Ziderman, Y., David, J., Berkovich-Ohana, A.
Open Accessindividual

Meditation, psychedelics, and brain connectivity: A randomized controlled resting-state fMRI study of N,N-dimethyltryptamine and harmine in a meditation retreat

In a double-blind, placebo-controlled resting-state fMRI study of 40 meditation practitioners, buccal DMT–harmine increased functional connectivity within the visual network and between visual and attention/salience networks, whereas meditation with placebo produced greater network segregation. No prolonged disruption of cortical gradients was observed, indicating a return to typical brain organisation shortly after the experience and pointing to distinct neural mechanisms — and potential clinical complementarities — between meditation and psychedelic-augmented meditation.

Published
September 29, 2025
Journal
Imaging Neuroscience
Authors
Egger, K., Meling, D., Polat, F., Seifritz, E., Avram, M., Scheidegger, M.
Open Accessindividual

Ayahuasca-assisted meaning reconstruction therapy as an early resource for bereavement: a non-randomized clinical trial

In this non-randomised, three-arm clinical trial of 84 adults bereaved within 12 months, ayahuasca-assisted meaning reconstruction therapy (A-MR) was well tolerated and produced significantly larger reductions in grief severity and greater improvements in prolonged grief symptoms, post‑traumatic growth and quality of life than meaning reconstruction alone or no treatment. These preliminary findings support A-MR as a potentially effective early intervention for severe grief but require replication in larger randomised trials.

Published
September 1, 2025
Journal
Scientific Reports
Authors
Soto-Angona, Ó., Andión, O., Sabucedo, P., Neimeyer, R. A., Haro, J. M., Javkin, J., Farré, M., González, D.
Open Accessindividual

Exploring the Therapeutic Effects of Psychedelics Administered to Military Veterans in Naturalistic Retreat Settings

Veterans attending naturalistic psilocybin or ayahuasca retreats showed significant improvements across eight mental‑health and reintegration measures, with the largest reductions in depression (PHQ‑9, 29.1%) and PTSD (PCL‑5, 26.1%). Psilocybin retreats produced greater gains on most outcomes while ayahuasca yielded slightly larger PTSD improvement; those with worse baseline symptoms benefited most, with some gender-specific differences.

Published
July 7, 2025
Journal
Brain and Behavior
Authors
Calnan, M., Blest-Hopley, G., Busch, C., Adams, M., Ruffell, S. G. D., Piper, T., Roseman, L., Kettner, H., Carhart-Harris, R.

Clinical Trials

3 trials
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
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
Completed

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: An Open-Label SPECT Neuroimaging Study

This unregistered trial (n=17) was an open-label, single-arm pilot study of ayahuasca for recurrent depression in adults, which demonstrated significant, sustained reductions in depressive symptoms alongside changes in regional cerebral blood flow.

Started
January 1, 2012
Type
interventional
Randomized
No
Registry ID
SANCHES-2016-JCP-AYAHUASCA-SPECT

Explore further

Search all Ayahuasca papers Search all Depressive Disorders trials Full Ayahuasca profile Full Depressive Disorders profile