Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial methods
Show snapshot details
On this page
This experiment, in seven questions
Jump straight to the part of the recipe you need. Data and provenance labels stay close to the action they support.
Shopping and prep list
What do I need before I start?
Biological model pending
Subject model for the experiment.
- Use
- confirm full cohort details in the source paper
Before you run
What should be confirmed before execution?
First confirmation
Species or subject information is missing.
Confirm before execution
Protocol does not list structured equipment.
Confirm before execution
This page shows passages quoted from the paper. Equipment, materials, times, and temperatures are hidden until the page is rebuilt from the full paper and checked by a reviewer. Check the paper before using this method.
Confirm before execution
Open the source paper before finalizing run-specific details.
Procurement checkpoint
Use source-stated vendors where present. Treat mapped products as sourcing options unless the page marks an exact source match.
Open quote workflowStep-by-step procedure
What do I do, in order?
Methods
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
Procedures
After screening, patients underwent a washout period of 2 weeks on average and adjusted to the half-life time of the antidepressant medication in use. During dosing session, patients were not under any antidepressant medication, and a new treatment scheme was introduced only 7 days after dosing. If needed, benzodiazepines were allowed as a supporting hypnotic and/or anxiolytic agents (online Supplementary Table S2 for demographic and clinical characteristics).
Procedures
Dosing sessions lasted approximately 8 h, from 8:00 a.m. to 4:00 p.m., and intake usually occurred at 10:00 a.m. After a light breakfast, patients were reminded about the effects they could experience, and strategies to help alleviating eventual difficulties. Patients were also told that they could receive ayahuasca and feel nothing, or placebo and feel something. Sessions took place in a quiet and comfortable living room-like environment, with a bed, a recliner, controlled temperature, natural, and dimmed light.
Procedures
Patients received a single dose of 1 ml/kg of placebo or ayahuasca adjusted to contain 0.36 mg/kg of N, N-DMT. They were asked to remain quiet, with their eyes closed, while focusing on their body, thoughts, and emotions. They were also allowed to listen to a predefined music playlist. Patients received support throughout the session from at least two investigators who remained in a room next door, offering assistance when needed. Acute effects were assessed with the Clinician-Administered Dissociative States Scale (CADSS) (Bremner et al., ), the Brief Psychiatric Rating Scale (BPRS) (Crippa et al., ), and the Young Mania Rating Scale (YMRS) (Vilela et al., ), applied at -10 min, +1:40 h, +2:40 h, and +4:00 h after intake.
Procedures
When the acute psychedelic effects ceased, patients had a last psychiatric evaluation, debriefed their experience, and responded to the Hallucinogenic Rating Scale (HRS) (Strassman et al., ) and Mystical Experience Questionnaire (MEQ30) (MacLean et al., ). Around 4:00 p.m. they could go home accompanied by a relative or friend. Only four patients presenting a more delicate condition remained as inpatients in the hospital ward for an entire week. Patients were asked to return for follow-up assessments at 1, 2, and 7 days after dosing.
Outcomes
The primary outcome measure was the change in depression severity assessed by the HAM-D scale, comparing baseline with seven days (D7) after dosing. The secondary outcome was the change in MADRS scores from baseline to 1 (D1), 2 (D2), and 7 (D7) days after dosing. We examined the proportion of patients meeting response criteria, defined as a reduction of 50% or more in baseline scores. Remission rates were also examined and were defined as HAM-D⩽7 or MADRS⩽10. We assessed response and remission rates using HAM-D (at D7) and MADRS (at D1, D2, and D7) scores. Safety and tolerability were assessed with the CADSS, the BPRS, and the YMRS applied during dosing session. We used the HRS and the MEQ30 to assess specific aspects of the psychedelic effects.
Statistical analysis
Analyses adhered to a modified intent-to-treat principle, including all patients who completed assessments at baseline, dosing and D7. An estimated sample size of 42 patients was estimated in G*Power software to provide 80% power to detect a five-point HAM-D difference (standardized effect size = 0.9) between baseline and D7 with two-sided 5% significance. The initial estimation was based on our previous open-label trial with ayahuasca in treatment-resistant depression (Sanches et al., ). A fixed-effects linear mixed model, with baseline scores as covariate, examined changes in HAM-D at D7, and MADRS at D1, D2, and D7. A Toeplitz covariance structure was the best fit to the data according to Akaike's information criterion. Missing data were estimated using restricted maximum-likelihood estimation. Main effects and treatment v. time interaction were evaluated. Post-hoc t tes...
Measurement outputs
What raw and processed outputs should exist?
Analysis plan
How should the outputs become interpretable results?
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
inferred from protocolPreprocessing / cleaning
Review raw outputs for quality, remove unusable captures, and organize the data into a comparison-ready table or image set.
inferred from protocolScoring or quantification
Quantify the primary endpoint described in the methods before moving into any statistical comparison.
inferred from protocolStatistical comparison
Statistical method not yet structured for this page.
inferred from protocolReporting output
Report representative outputs alongside the summary comparison used to support the conclusion.
inferred from protocolSource and audit
What supports the facts on this page?
Evidence quotes (7)
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
After screening, patients underwent a washout period of 2 weeks on average and adjusted to the half-life time of the antidepressant medication in use. During dosing session, patients were not under any antidepressant medication, and a new treatment scheme was introduced only 7 days after dosing. If needed, benzodiazepines were allowed as a supporting hypnotic and/or anxiolytic agents (online Supplementary Table S2 for demographic and clinical characteristics).
Dosing sessions lasted approximately 8 h, from 8:00 a.m. to 4:00 p.m., and intake usually occurred at 10:00 a.m. After a light breakfast, patients were reminded about the effects they could experience, and strategies to help alleviating eventual difficulties. Patients were also told that they could receive ayahuasca and feel nothing, or placebo and feel something. Sessions took place in a quiet and comfortable living room-like environment, with a bed, a recliner, controlled temperature, natural, and dimmed light.
Patients received a single dose of 1 ml/kg of placebo or ayahuasca adjusted to contain 0.36 mg/kg of N, N-DMT. They were asked to remain quiet, with their eyes closed, while focusing on their body, thoughts, and emotions. They were also allowed to listen to a predefined music playlist. Patients received support throughout the session from at least two investigators who remained in a room next door, offering assistance when needed. Acute effects were assessed with the Clinician-Administered Dissociative States Scale (CADSS) (Bremner et al., ), the Brief Psychiatric Rating Scale (BPRS) (Crippa et al., ), and the Young Mania Rating Scale (YMRS) (Vilela et al., ), applied at -10 min, +1:40 h, +2:40 h, and +4:00 h after intake.
When the acute psychedelic effects ceased, patients had a last psychiatric evaluation, debriefed their experience, and responded to the Hallucinogenic Rating Scale (HRS) (Strassman et al., ) and Mystical Experience Questionnaire (MEQ30) (MacLean et al., ). Around 4:00 p.m. they could go home accompanied by a relative or friend. Only four patients presenting a more delicate condition remained as inpatients in the hospital ward for an entire week. Patients were asked to return for follow-up assessments at 1, 2, and 7 days after dosing.
The primary outcome measure was the change in depression severity assessed by the HAM-D scale, comparing baseline with seven days (D7) after dosing. The secondary outcome was the change in MADRS scores from baseline to 1 (D1), 2 (D2), and 7 (D7) days after dosing. We examined the proportion of patients meeting response criteria, defined as a reduction of 50% or more in baseline scores. Remission rates were also examined and were defined as HAM-D⩽7 or MADRS⩽10. We assessed response and remission rates using HAM-D (at D7) and MADRS (at D1, D2, and D7) scores. Safety and tolerability were assessed with the CADSS, the BPRS, and the YMRS applied during dosing session. We used the HRS and the MEQ30 to assess specific aspects of the psychedelic effects.
Analyses adhered to a modified intent-to-treat principle, including all patients who completed assessments at baseline, dosing and D7. An estimated sample size of 42 patients was estimated in G*Power software to provide 80% power to detect a five-point HAM-D difference (standardized effect size = 0.9) between baseline and D7 with two-sided 5% significance. The initial estimation was based on our previous open-label trial with ayahuasca in treatment-resistant depression (Sanches et al., ). A fixed-effects linear mixed model, with baseline scores as covariate, examined changes in HAM-D at D7, and MADRS at D1, D2, and D7. A Toeplitz covariance structure was the best fit to the data according to Akaike's information criterion. Missing data were estimated using restricted maximum-likelihood estimation. Main effects and treatment v. time interaction were evaluated. Post-hoc t tests were performed for between-groups comparisons at all time points, and Sidak's test was used to control for multiple comparisons. Cohen's d effect sizes were obtained for between and within group comparisons. Between-group effect sizes were calculated using the estimated means of each group at eac...
Machine-readable layer
[
{
"@context": "https://schema.org",
"@type": "HowTo",
"name": "Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial methods",
"description": "Protocol for Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial methods",
"step": [
{
"@type": "HowToStep",
"position": 1,
"name": "Methods",
"text": "To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing."
},
{
"@type": "HowToStep",
"position": 2,
"name": "Procedures",
"text": "After screening, patients underwent a washout period of 2 weeks on average and adjusted to the half-life time of the antidepressant medication in use. During dosing session, patients were not under any antidepressant medication, and a new treatment scheme was introduced only 7 days after dosing. If needed, benzodiazepines were allowed as a supporting hypnotic and/or anxiolytic agents (online Supplementary Table S2 for demographic and clinical characteristics)."
},
{
"@type": "HowToStep",
"position": 3,
"name": "Procedures",
"text": "Dosing sessions lasted approximately 8 h, from 8:00 a.m. to 4:00 p.m., and intake usually occurred at 10:00 a.m. After a light breakfast, patients were reminded about the effects they could experience, and strategies to help alleviating eventual difficulties. Patients were also told that they could receive ayahuasca and feel nothing, or placebo and feel something. Sessions took place in a quiet and comfortable living room-like environment, with a bed, a recliner, controlled temperature, natural, and dimmed light."
},
{
"@type": "HowToStep",
"position": 4,
"name": "Procedures",
"text": "Patients received a single dose of 1 ml/kg of placebo or ayahuasca adjusted to contain 0.36 mg/kg of N, N-DMT. They were asked to remain quiet, with their eyes closed, while focusing on their body, thoughts, and emotions. They were also allowed to listen to a predefined music playlist. Patients received support throughout the session from at least two investigators who remained in a room next door, offering assistance when needed. Acute effects were assessed with the Clinician-Administered Dissociative States Scale (CADSS) (Bremner et al., ), the Brief Psychiatric Rating Scale (BPRS) (Crippa et al., ), and the Young Mania Rating Scale (YMRS) (Vilela et al., ), applied at -10 min, +1:40 h, +2:40 h, and +4:00 h after intake."
},
{
"@type": "HowToStep",
"position": 5,
"name": "Procedures",
"text": "When the acute psychedelic effects ceased, patients had a last psychiatric evaluation, debriefed their experience, and responded to the Hallucinogenic Rating Scale (HRS) (Strassman et al., ) and Mystical Experience Questionnaire (MEQ30) (MacLean et al., ). Around 4:00 p.m. they could go home accompanied by a relative or friend. Only four patients presenting a more delicate condition remained as inpatients in the hospital ward for an entire week. Patients were asked to return for follow-up assessments at 1, 2, and 7 days after dosing."
},
{
"@type": "HowToStep",
"position": 6,
"name": "Outcomes",
"text": "The primary outcome measure was the change in depression severity assessed by the HAM-D scale, comparing baseline with seven days (D7) after dosing. The secondary outcome was the change in MADRS scores from baseline to 1 (D1), 2 (D2), and 7 (D7) days after dosing. We examined the proportion of patients meeting response criteria, defined as a reduction of 50% or more in baseline scores. Remission rates were also examined and were defined as HAM-D⩽7 or MADRS⩽10. We assessed response and remission rates using HAM-D (at D7) and MADRS (at D1, D2, and D7) scores. Safety and tolerability were assessed with the CADSS, the BPRS, and the YMRS applied during dosing session. We used the HRS and the MEQ30 to assess specific aspects of the psychedelic effects."
},
{
"@type": "HowToStep",
"position": 7,
"name": "Statistical analysis",
"text": "Analyses adhered to a modified intent-to-treat principle, including all patients who completed assessments at baseline, dosing and D7. An estimated sample size of 42 patients was estimated in G*Power software to provide 80% power to detect a five-point HAM-D difference (standardized effect size = 0.9) between baseline and D7 with two-sided 5% significance. The initial estimation was based on our previous open-label trial with ayahuasca in treatment-resistant depression (Sanches et al., ). A fixed-effects linear mixed model, with baseline scores as covariate, examined changes in HAM-D at D7, and MADRS at D1, D2, and D7. A Toeplitz covariance structure was the best fit to the data according to Akaike's information criterion. Missing data were estimated using restricted maximum-likelihood estimation. Main effects and treatment v. time interaction were evaluated. Post-hoc t tes..."
}
],
"tool": [],
"supply": [],
"isBasedOn": {
"@type": "ScholarlyArticle",
"headline": "Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial",
"datePublished": "2019",
"author": [
{
"@type": "Person",
"name": "Fernanda Palhano-Fontes"
},
{
"@type": "Person",
"name": "Dayanna Barreto"
},
{
"@type": "Person",
"name": "Heloisa Onias"
},
{
"@type": "Person",
"name": "Katia C. Andrade"
},
{
"@type": "Person",
"name": "Morgana M. Novaes"
},
{
"@type": "Person",
"name": "Jessica A. Pessoa"
},
{
"@type": "Person",
"name": "Sergio A. Mota-Rolim"
},
{
"@type": "Person",
"name": "Flávia L. Osório"
},
{
"@type": "Person",
"name": "Rafael Sanches"
},
{
"@type": "Person",
"name": "Rafael G. dos Santos"
},
{
"@type": "Person",
"name": "Luís Fernando Tófoli"
},
{
"@type": "Person",
"name": "Gabriela de Oliveira Silveira"
},
{
"@type": "Person",
"name": "Mauricio Yonamine"
},
{
"@type": "Person",
"name": "Jordi Riba"
},
{
"@type": "Person",
"name": "Francisco R. Santos"
},
{
"@type": "Person",
"name": "Antonio A. Silva-Junior"
},
{
"@type": "Person",
"name": "João C. Alchieri"
},
{
"@type": "Person",
"name": "Nicole L. Galvão-Coelho"
},
{
"@type": "Person",
"name": "Bruno Lobão-Soares"
},
{
"@type": "Person",
"name": "Jaime E. C. Hallak"
},
{
"@type": "Person",
"name": "Emerson Arcoverde"
},
{
"@type": "Person",
"name": "João P. Maia-de-Oliveira"
},
{
"@type": "Person",
"name": "Dráulio B. Araújo"
}
],
"identifier": "10.1017/s0033291718001356"
}
},
{
"@context": "https://schema.org",
"@type": "BreadcrumbList",
"itemListElement": [
{
"@type": "ListItem",
"position": 1,
"name": "Experiments",
"item": "https://replicatescience.com/experiments"
},
{
"@type": "ListItem",
"position": 2,
"name": "Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial methods",
"item": "https://replicatescience.com/experiments/rapid-antidepressant-effects-of-the-psychedelic-ayahuasca-in-treatment-resistant-depression-a-randomized-placebo-controlled-trial-methods-fernanda-palhano-fontes-pmc6378413/rapid-antidepressant-effects-of-the-psychedelic-ayahuasca-in-treatment-resistant-depression-a-random-mlpgxpho"
}
]
}
]