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

Major Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02914769
• Other study ID #: CNPq-466760/2014-0
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 21, 2016
• Last updated: February 15, 2017
• Start date: February 2014
• Est. completion date: December 2016

Study information

• Verified date: February 2017
• Source: Universidade Federal do Rio Grande do Norte
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depression

Intervention

Drug:
• Ayahuasca
patients will receive a single dose of ayahuasca.
• placebo
patients will receive a single dose of a passive placebo.

Locations

Country	Name	City	State
Brazil	Draulio B de Araujo	Natal	Rio Grande do Norte

Sponsors (2)

Lead Sponsor	Collaborator
Universidade Federal do Rio Grande do Norte	University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

Osório 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. Rev Bras Psiquiatr. 2015 Jan-Mar;37(1):13-20. doi: 10.1590/1516-4446-2014-1496. — View Citation

Sanches RF, de Lima Osório 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HAM-D effect at D7	changes in depression severity, assessed by HAM-D scale, from baseline to 7 days after dosing	seven days after dosing
Secondary	MADRS effect at D1, D2 and D7	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
Secondary	Response rate at D7 (HAM-D)	response rate: reduction of 50% or more in baseline scores, assessed seven days after dosing by the HAM-D scale.	seven days after dosing
Secondary	Response rate at D1, D2 and D7 (MADRS)	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
Secondary	Remission rate at D7 (HAM-D)	remission rate: HAM-D=7 at D7.	seven days after dosing
Secondary	Remission rate at D1, D2 and D7 (MADRS)	remission rate: MADRS=10 at D1, D2 and D7	one, two and seven days after dosing