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 4 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 between-group effect sizes increasing from d=0.84 to d=1.49.
Synthesized
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State of the evidence: Anxiety Supports
Ayahuasca produced significantly greater reductions in depression severity than placebo at all time points over seven days, with large effect sizes.
Synthesized
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State of the evidence: Ayahuasca Supports
Ayahuasca produced significantly greater reductions in depression severity than placebo at all measured time points over seven days, with effect sizes increasing from day 1 to day 7.
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 |