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

NCT02914769 | Completed Phase 1 Results DMC

• 1 other identifier: CNPq-466760/2014-0
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depression

Keywords

Depression; Ayahuasca; Psychedelics

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)

  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 score indicates less severe depression (better outcome). Usual cutoff points are a total score ranging from: 0 to 7 indicates that the patient is in the normal range (no depression); 8 to 16 indicates "mild depression"; 17 to 23 indicates "moderate depression"; a score of 24 and greater indicates "severe depression".

  seven days after dosing

Secondary Outcomes (5)

• Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7

  one, two and seven days after dosing

• Number of Participants With Reduction of 50% or More in Hamilton Depression Rating Scale(HAM-D) Scores at D7

  seven days after dosing

• Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7

  one, two, and seven days after dosing

• Number of Participants With a Score Lower Then or Equal to 7 in the Hamilton Depression Rating Scale (HAM-D) at D7

  seven days after dosing

• Number of Participants With a Score Lower Then or Equal to 10 in the Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7

  one, two and seven days after dosing

Study Arms (2)

placebo

PLACEBO COMPARATOR

patients receiving a passive placebo

Drug: placebo

Ayahuasca

EXPERIMENTAL

patients receiving Ayahuasca

Drug: Ayahuasca

Interventions

Ayahuasca DRUG

patients will receive a single dose of ayahuasca.

Also known as: treatment

Ayahuasca

placebo DRUG

patients will receive a single dose of a passive placebo.

placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18-60 years old;
• Diagnostic of major depressive disorder (DSM-IV);
• At least two previous unsuccessful antidepressant medications;
• Current depressive episode (HAM-D \>= 17).

You may not qualify if:

• History of psychosis;
• Present or past history of bipolar disorder or schizophrenia;
• Diagnosis of current clinical disease, based on history, physical examination and routine hematologic and biochemical tests;
• Serious and imminent suicidal risk;
• Pregnancy, current drug or alcohol dependence;
• Previous experience with ayahuasca.

Sponsors & Collaborators

• Universidade Federal do Rio Grande do Norte: lead
• University of Sao Paulo: collaborator

Study Sites (1)

Draulio B de Araujo

Natal, Rio Grande do Norte, 59012-300, Brazil

Location

Related Publications (5)

• Sanches RF, de Lima Osorio F, Dos Santos RG, Macedo LR, Maia-de-Oliveira JP, Wichert-Ana L, de Araujo DB, Riba J, Crippa JA, Hallak JE. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study. J Clin Psychopharmacol. 2016 Feb;36(1):77-81. doi: 10.1097/JCP.0000000000000436.

  PMID: 26650973 BACKGROUND

• Osorio Fde L, Sanches RF, Macedo LR, Santos RG, Maia-de-Oliveira JP, Wichert-Ana L, Araujo DB, Riba J, Crippa JA, Hallak JE. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Braz J Psychiatry. 2015 Jan-Mar;37(1):13-20. doi: 10.1590/1516-4446-2014-1496.

  PMID: 25806551 BACKGROUND

• Zeifman RJ, Palhano-Fontes F, Hallak J, Arcoverde E, Maia-Oliveira JP, Araujo DB. The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial. Front Pharmacol. 2019 Nov 19;10:1325. doi: 10.3389/fphar.2019.01325. eCollection 2019.

  PMID: 31798447 DERIVED

• de Almeida RN, Galvao ACM, da Silva FS, Silva EADS, Palhano-Fontes F, Maia-de-Oliveira JP, de Araujo LB, Lobao-Soares B, Galvao-Coelho NL. Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial. Front Psychol. 2019 Jun 4;10:1234. doi: 10.3389/fpsyg.2019.01234. eCollection 2019.

  PMID: 31231276 DERIVED

• Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, Pessoa JA, Mota-Rolim SA, Osorio FL, Sanches R, Dos Santos RG, Tofoli LF, de Oliveira Silveira G, Yonamine M, Riba J, Santos FR, Silva-Junior AA, Alchieri JC, Galvao-Coelho NL, Lobao-Soares B, Hallak JEC, Arcoverde E, Maia-de-Oliveira JP, Araujo DB. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019 Mar;49(4):655-663. doi: 10.1017/S0033291718001356. Epub 2018 Jun 15.

  PMID: 29903051 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Draulio Barros de Araujo
• Organization: UFRN

draulio@neuro.ufrn.br

+5584991225987

Study Officials

• Draulio B de Araujo, Ph.D

  Brain Institute - UFRN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: September 26, 2016
• Study Start: February 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 6, 2025
• Results First Posted: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)