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

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ClinicalTrials.gov Identifier: NCT02914769
Recruitment Status : Completed
First Posted : September 26, 2016
Last Update Posted : February 17, 2017
Sponsor:
Collaborator:
University of Sao Paulo
Information provided by (Responsible Party):
Draulio Barros de Araujo, Universidade Federal do Rio Grande do Norte

Tracking Information
First Submitted Date  ICMJE September 21, 2016
First Posted Date  ICMJE September 26, 2016
Last Update Posted Date February 17, 2017
Study Start Date  ICMJE February 2014
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
HAM-D response [ Time Frame: seven days after intervention ]
response: reduction of at least 50% in depression severity according to the HAM-D scale, with respect to baseline.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2017)
  • 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
  • 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.
  • 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.
  • Remission rate at D7 (HAM-D) [ Time Frame: seven days after dosing ]
    remission rate: HAM-D≤7 at D7.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
  • HAM-D interaction [ Time Frame: seven days after intervention ]
    Interaction (time x drug) observed from scores in the HAM-D scale at baseline with respect to 7 days after intervention
  • MADRS interaction [ Time Frame: day 1, day 2, day 7 ]
    Interaction (time x drug) observed from scores in the HAM-D scale at baseline with respect to days 1, 2 and 7 after intervention
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression
Official Title  ICMJE Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Major Depression
Intervention  ICMJE
  • Drug: Ayahuasca
    patients will receive a single dose of ayahuasca.
  • Drug: placebo
    patients will receive a single dose of a passive placebo.
Study Arms  ICMJE
  • Placebo Comparator: placebo
    patients receiving a passive placebo
    Intervention: Drug: placebo
  • Experimental: Ayahuasca
    patients receiving Ayahuasca
    Intervention: Drug: Ayahuasca
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 15, 2017)
35
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2016)
50
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02914769
Other Study ID Numbers  ICMJE CNPq-466760/2014-0
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Draulio Barros de Araujo, Universidade Federal do Rio Grande do Norte
Study Sponsor  ICMJE Universidade Federal do Rio Grande do Norte
Collaborators  ICMJE University of Sao Paulo
Investigators  ICMJE
Principal Investigator: Draulio B de Araujo, Ph.D Brain Institute - UFRN
PRS Account Universidade Federal do Rio Grande do Norte
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP