Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias, Kátia C. Andrade, Morgana Menezes Novaes, Jéssica Andrade Pessoa, Sérgio Mota-Rolim, Flávia de Lima Osório, Rafael Faria Sanches, Rafael G. Dos Santos, Luís Fernando Tófoli, Gabriela de Oliveira Silveira, Maurı́cio Yonamine, Jordi Riba, Francisco R. Santos, Antonio A Silva-Junior, João Carlos Alchieri, Nicole Leite Galvão‐coelho, Bruno Lobão‐soares, Jaime E. C. Hallak, Emerson Arcoverde, João Paulo Maia‐de‐oliveira, Dráulio Barros de Araújo
Psychological Medicine June 15, 2018 DOI: 10.1017/s0033291718001356 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Open-label Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Patients with treatment-resistant depression |
| Intervention | Ayahuasca |
| Dose | single dose |
| Duration | 7 days |
| Topics | Anxiety Ayahuasca Depression |
| Keywords | Placebo Depression economics Antidepressant Randomized controlled trial Rating scale Hallucinogen Alternative medicine |
| Citations | 827 |
| Registration | NCT02914769 |
| Key findings | Ayahuasca produced significantly greater reductions in depression severity than placebo at all measured time points over seven days in patients with treatment-resistant depression. |
Abstract
Abstract Background Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
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.
Results: We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 ( p = 0.04), and at D7 ( p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
Conclusions: To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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A single ayahuasca dose produced significantly greater reductions in depression severity than placebo at all time points over seven days, with large between-group effect sizes.
Synthesized
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A single dose of ayahuasca produced significantly greater reductions in depression severity than placebo at days 1, 2, and 7, with effect sizes increasing to d=1.49 at day 7.
Synthesized
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State of the evidence: Ayahuasca Supports
A single ayahuasca dose produced significantly greater reductions in depression severity than placebo at all time points over seven days, with effect sizes increasing from d=0.84 at day 1 to d=1.49 at day 7 and higher response rates at day 7 (64% vs 27%).
Synthesized
Comparable studies
Other randomized controlled trials on ayahuasca for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls Treatment-resistant depression patients and healthy volunteers | 2018 | Randomized controlled trial | |
| Acute effects of ayahuasca in a juvenile non-human primate model of depression Juvenile marmosets (Callithrix jacchus), 8 males and 7 females | 2018 | Randomized controlled trial | n = 15 |
| A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression Patients with treatment-resistant depression | 2017 | Parallel-arm, double-blind randomized placebo-controlled trial | n = 29 |
| Moderators of ayahuasca’s biological antidepressant action Patients with treatment-resistant depression and healthy volunteers | 2022 | Randomized double-blinded, placebo-controlled trial | n = 72 |
| A Single Dose Of Ayahuasca Modulates Salivary Cortisol In Treatment-Resistant Depression Treatment-resistant depressed patients and healthy volunteers | 2018 | Randomized placebo-controlled trial |
Citations in the library
Cited by 702
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioral Science 2020
- Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Acta Psychiatrica Scandinavica October 30, 2020
- Neural correlates of the DMT experience assessed with multivariate EEG. Scientific Reports November 19, 2019
and 697 more in the library
Cites 32
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 27 more in the library