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

February 15, 2017 updated by: Draulio Barros de Araujo, Universidade Federal do Rio Grande do Norte
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

1) Background

The therapeutic effectiveness of currently available antidepressant is low. Less than 50% of the patients achieve remission after single treatment, and about 30% after four different treatments. Besides low response rates, pharmacological treatment are associated with several side effects and response onset is usually long (~2-3 weeks). Thus, great effort has been made to the development of alternative antidepressants. For instance, ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and potent antidepressant effects in treatment of major depressive and bipolar disorders.

This proposal aims at testing the antidepressant effects of Ayahuasca, traditionally prepared by decoction of two plants: Psychotria viridis and Banisteriopsis caapi, long used by Amazonian Amerindians. P. viridis is a rich source of the serotonergic agonist N,N-dimethyltryptamine (DMT), whereas B. caapi contains potent monoamine oxidase-A inhibitors (MAOi-A) such as harmine, harmaline, and tetrahydroharmine, a serotonin reuptake inhibitor.

Common effects of Ayahuasca include sedation, gastrointestinal distress, changes of spatiotemporal scaling, dissociation, sense of well-being, insights, feelings of apprehension, increased interoceptive attention and sensory pseudo-hallucinations. Effects begin at 30-40 min after oral intake, and last up to 4 hours. Previous studies suggest the absence of psychological, neuropsychological or psychiatric harm caused by prolonged Ayahuasca consumption, and it is not addictive, on the contrary, it also shows promise in treating addiction.

Recently, two preliminary open label studies have tested tolerability, safety and the antidepressant effect of Ayahuasca in treatment-resistant depression. In the first study, six patients were recruited, in the second, 17 patients. The results show significant decrease in depression severity (HAM-D & MADRS scales) already at 2 hours after intake, which lasted for 21 days. Although the results are promising, they must be considered with caution, specially due to the lack of control of the placebo effect, which is generally high in clinical trials.

Thus, the present study is a randomized placebo-controlled trial in 50 patients with treatment resistant depression. Besides the Antidepressant effects of Ayahuasca, this study will also evaluate 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 and psychiatric scales and questionnaires.

2. Methods

All 50 patients will undergo routine evaluation, including complete blood testing for individual glycemic profile, serum cholesterol and triglyceride, plasma sodium and potassium, urea and creatinine.

Patients will undergo a wash-out period, between 7 and 14 days prior to the experimental session, depending on the lifetime of the antidepressant in use. Experiments will take place at the Hospital Universitário Onofre Lopes, a tertiary university hospital affiliated to the Universidade Federal do Rio Grande do Norte (UFRN), Brazil.

In the treatment session, 25 patients will drink Ayahuasca, 25 will drink an inert placebo. Psychiatric scales (HAM-D, MADRS, BPRS, CADSS and YMRS) will be completed during treatment session, day one before (-D1), one day after (+D1), two days (+D2), seven days (+D7), fourteen days (+D14), one month (+M1), and up to six months (+M6) following the treatment session. The following exams will also be conducted at D-1 and D+1: neuropsychological tests (watch test, trail test, and N-back), structural and functional MRI, polysomnography and blood testing (BDNF, TNF-a, cortisol, oxytocin, IL-6, and IL-10).

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59012-300
        • Draulio B de Araujo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: placebo
patients receiving a passive placebo
Drug: placebo
patients will receive a single dose of a passive placebo.
Experimental: Ayahuasca
patients receiving Ayahuasca
Drug: Ayahuasca
patients will receive a single dose of ayahuasca.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HAM-D effect at D7
Time Frame: seven days after dosing
changes in depression severity, assessed by HAM-D scale, from baseline to 7 days after dosing
seven days after dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MADRS effect at D1, D2 and D7
Time Frame: one, two and seven days after dosing
changes in depression severity, assessed by MADRS scale, from baseline to 1 day, 2 days, and 7 days after dosing
one, two and seven days after dosing
Response rate at D7 (HAM-D)
Time Frame: seven days after dosing
response rate: reduction of 50% or more in baseline scores, assessed seven days after dosing by the HAM-D scale.
seven days after dosing
Response rate at D1, D2 and D7 (MADRS)
Time Frame: one, two, and seven days after dosing
response rate: reduction of 50% or more in baseline scores, assessed at one day, two days and seven days after dosing by the MADRS scale.
one, two, and seven days after dosing
Remission rate at D7 (HAM-D)
Time Frame: seven days after dosing
remission rate: HAM-D≤7 at D7.
seven days after dosing
Remission rate at D1, D2 and D7 (MADRS)
Time Frame: one, two and seven days after dosing
remission rate: MADRS≤10 at D1, D2 and D7
one, two and seven days after dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidade Federal do Rio Grande do Norte

Collaborators

University of Sao Paulo

Investigators

  • Principal Investigator: Draulio B de Araujo, Ph.D, Brain Institute - UFRN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

September 21, 2016

First Submitted That Met QC Criteria

September 23, 2016

First Posted (Estimate)

September 26, 2016

Study Record Updates

Last Update Posted (Actual)

February 17, 2017

Last Update Submitted That Met QC Criteria

February 15, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CNPq-466760/2014-0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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