A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression
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
bioRxiv (Cold Spring Harbor Laboratory) January 27, 2017 preprint DOI: 10.1101/103531 via OpenAlex
Summary
AI-generated from the abstractA single dose of ayahuasca produced significant antidepressant effects in patients with treatment-resistant depression compared to placebo. Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), was significantly lower in the ayahuasca group at one, two, and seven days after dosing. Effect sizes increased over time, reaching a Cohen's d of 1.49 at day seven. Response rates were significantly higher in the ayahuasca group at day seven (64% vs. 27%), and remission rates were marginally significant (36% vs. 7%). This controlled trial supports the safety and therapeutic value of ayahuasca in treating depression.
Study at a glance
| Characteristics | Parallel-arm, double-blind randomized placebo-controlled trial Open-label |
|---|---|
| Sample size | 29 |
| Population | Patients with treatment-resistant depression |
| Intervention | Ayahuasca |
| Dose | single dose |
| Duration | 7-day follow-up |
| Topics | Anxiety Ayahuasca Depression |
| Keywords | Placebo Depression economics Antidepressant |
| Citations | 22 |
| Key finding | Ayahuasca significantly reduced depression severity compared to placebo at all timepoints measured, with a large effect size at day seven. |
Abstract
Abstract Recent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further 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. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to 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% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). 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.