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 via OpenAlex
Summary
AI-generated from the abstractA single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Study at a glance
| 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 |
| Citations | 827 |
| Registration | NCT02914769 |
| Key finding | 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).