NCT02914769

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

Completed Phase 1/Phase 2 Results posted Last updated 4 April 2025

What this trial tests

Phase 1/Phase 2 trial testing Ayahuasca in Major Depression in 35 participants. Completed in 1 December 2016.

Timeline

1 February 2014

Primary endpoint
1 December 2016

1 December 2016

Quick facts

Lead sponsor	Universidade Federal do Rio Grande do Norte
Phase	Phase 1/Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	35
Start date	1 February 2014
Primary completion	1 December 2016
Estimated completion	1 December 2016
Sites	1 location across Brazil

Drugs / interventions tested

• Ayahuasca — full drug profile →
• placebo

Conditions studied

• Major Depression — all drugs for Major Depression →

Sponsor

Universidade Federal do Rio Grande do Norte — full company profile →

Who can join

Adults 18 to 60, any sex, with Major Depression. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)
  Time frame: seven days after dosing
  changes in depression severity, assessed by the Hamilton Depression Rating Scale (HAM-D) scale, from baseline to 7 days after dosing. Minimum and maximum scores are 0 and 50, respectively. Although the HAM-D form lists 21 items, the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored from 0-2. Lower HAM-D

Sponsor's own description

The purpose of the present trial is to test the efficacy of Ayahuasca in treatment-resistant depression. Ayahuasca is a decoction of two plants, long used by Amazonian Amerindians. Traditionally, it is prepared by decoction of a bush (Psychotria viridis) with a liana (Banisteriopsis caapi). P. viridis is a rich source of N,N-dimethyltryptamine (DMT), a serotonergic agonist, and B. caapi contains potent monoamine oxidase-A inhibitors (MAOi-A), such as harmine, harmaline. The study is designed as a randomized placebo controlled trial with two parallel arms, and it will also evaluate changes of different biomarkers of depression including anatomical and functional Magnetic Resonance Imaging (MRI), serum levels of BDNF, TNF-a, cortisol, IL-6, and IL-10, polysomnography, neuropsychological, psychiatric scales and questionnaires.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.
   Palhano-Fontes F, Barreto D, Onias H, Andrade KC, et al · · 2019 · cited 514× · PMID 29903051 · DOI 10.1017/s0033291718001356
2. Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial.
   de Almeida RN, Galvão ACM, da Silva FS, Silva EADS, et al · · 2019 · cited 119× · PMID 31231276 · DOI 10.3389/fpsyg.2019.01234
3. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
   Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
4. Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls.
   Galvão ACM, de Almeida RN, Silva EADS, Freire FAM, et al · · 2018 · cited 72× · PMID 29867608 · DOI 10.3389/fpsyt.2018.00185
5. Novel drug developmental strategies for treatment-resistant depression.
   Borbély É, Simon M, Fuchs E, Wiborg O, et al · · 2022 · cited 70× · PMID 34822719 · DOI 10.1111/bph.15753
6. The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial.
   Zeifman RJ, Palhano-Fontes F, Hallak J, Arcoverde E, et al · · 2019 · cited 51× · PMID 31798447 · DOI 10.3389/fphar.2019.01325
7. Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry.
   Sakurai H, Yonezawa K, Tani H, Mimura M, et al · · 2022 · cited 21× · PMID 35045580 · DOI 10.1055/a-1714-9097
8. Changes in Cortisol but Not in Brain-Derived Neurotrophic Factor Modulate the Association Between Sleep Disturbances and Major Depression.
   Santiago GTP, de Menezes Galvão AC, de Almeida RN, Mota-Rolim SA, et al · · 2020 · cited 18× · PMID 32410966 · DOI 10.3389/fnbeh.2020.00044