This page follows a source whose reuse terms permit translation, preserving its structure and line of argument in English.
About this resource
This is an English version of a double-blind randomized trial that compared ayahuasca with placebo in patients with treatment-resistant depression. The authors assessed how depressive symptoms changed after a single research intervention in people who had not improved sufficiently with existing antidepressants, with evaluations 1 day, 2 days, and 7 days afterward. It is an important controlled clinical trial within ayahuasca research, but it included 29 participants and follow-up was primarily limited to 1 week.
The ayahuasca used here was a chemically analyzed research preparation and does not represent every diverse brew in circulation. The results are also limited to selected participants under medical supervision in a defined research setting. A “short-term change on a symptom scale” is a different question from “long-term therapeutic efficacy” or “safety in general settings.”
Study design
The trial was conducted at a research facility in Brazil. Participants were adults with moderate to severe depression who had not responded adequately to several antidepressants in the past. People with psychotic disorders, mania, and certain physical risks were excluded, and participants were randomized to an ayahuasca group or a placebo group whose color, taste, nausea, and other sensory qualities were designed to be similar. Both participants and raters were intended to be blinded.
The Montgomery–Åsberg Depression Rating Scale (MADRS) was a principal measure, with the Hamilton Depression Rating Scale (HAM-D) also used as a supplementary measure. Participants were assessed before the intervention and 1, 2, and 7 days afterward, and score changes, response rates, and remission rates were compared between groups. Trial registration and a statistical plan were reported, but with an intervention that has strong subjective effects, it is impossible to guarantee completely how well formal blinding held in practice.
Content
In their background discussion, the authors note that conventional antidepressants can take time to act and that options for patients with treatment-resistant depression are limited. Ayahuasca contains DMT and β-carboline alkaloids, which may act on the central nervous system in combination. This pharmacological account does not directly prove the cause of the clinical results; it provides background for the research hypothesis.
Psychological and physical reactions were also recorded during the trial. Acute perceptual changes and internal experiences may occur, as may nausea and vomiting. Researchers monitored participants and kept them under observation at the facility until the acute effects subsided. This framework is one reason the findings cannot be transferred directly to unsupervised use.
Results
MADRS scores decreased in both groups, but the strength of the between-group difference varied by time point. The authors reported changes favoring the ayahuasca group in some comparisons at 1, 2, and 7 days after the intervention. On day 7, the response rate was 64% in the ayahuasca group and 27% in the placebo group, while remission rates were 36% versus 7%. The between-group difference in remission, however, was not statistically clear, and with so few participants, a difference of only several people can substantially change these percentages.
Improvement in the placebo group is also important. The inpatient environment, expectations, contact with researchers, natural fluctuation, and other factors besides pharmacology could have affected both groups. The trial therefore shows that differences in short-term scales were observed under these conditions; it does not establish that the intervention works for every patient, prevents relapse, or is superior to existing treatments.
Limitations
The principal limitations are the sample of 29 participants and the short follow-up period. The study had insufficient power to assess rare adverse events, duration of effects, safety with repeated exposure, or comparisons with other treatments. Participants were selected in a single region, so the results cannot be generalized directly to the wider population of people with depression, people with comorbidities, or different age groups.
The distinctive subjective effects may also have allowed participants to infer their allocation. The placebo was designed to mimic sensory qualities, but functional unblinding cannot be ruled out completely. Rating scales are important clinical measures, but they do not fully represent everyday functioning, relapse, or long-term benefits and risks.
Expectations at enrollment, prior treatment history, and severity also differed among individuals. Prespecified primary outcomes and exploratory comparisons carry different evidentiary weight, and a difference at one time point should not be recast as a consistent difference across every time point. Response and remission rates also depend on the scales and thresholds used.
Safety
The safety findings from this trial are records from a small study with prior screening and medical monitoring. Nausea, vomiting, anxiety, perceptual changes, and changes in blood pressure or heart rate may be concerns. Risks differ with a history of psychotic or bipolar disorders, cardiovascular status, pregnancy, concomitant medication, and other factors; interactions with substances that affect monoamine systems in particular require individual assessment.
This page does not provide instructions for use or preparation. The observation that serious problems were not frequent in the study is not grounds for considering brews of unknown composition or unsupervised environments safe. Nor is this a resource recommending changes to depression treatment or discontinuation of medication.
Results from an intervention study need to be interpreted after considering diagnosis, medication history, physical condition, and available support. The article’s rank reflects editorial importance, not a ranking of treatment choices.
Completing the acute phase without incident is also different from remaining psychologically stable afterward. Outside research settings, adequate screening, emergency response, and follow-up may be absent. Individual contraindications, interactions, and crisis response must be considered before short-term average results.
Source and rights
Original source: Palhano-Fontes F, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine. 2019;49(4):655–663. DOI: 10.1017/S0033291718001356.
The original article is available under Creative Commons Attribution 4.0 (CC BY 4.0). This page is a source-aligned English translation under that license, with the structure reorganized for readability. Tables and figures are not reproduced, and the numbers and statements in the original source take precedence when interpreting the findings.