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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Randomized controlled trial Rating scale Hallucinogen Alternative medicine |
| Citations | 22 |
| Key findings | 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.
Comparable studies
Other randomized controlled trials on ayahuasca for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Patients with treatment-resistant depression | 2018 | Randomized controlled trial | n = 29 |
| 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 |
| 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 13
- Serotonergic psychedelics and personality: A systematic review of contemporary research Neuroscience & Biobehavioral Reviews February 13, 2018
- Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls Frontiers in Psychiatry May 8, 2018
- Ayahuasca use and reported effects on depression and anxiety symptoms: An international cross-sectional study of 11,912 consumers Journal of Affective Disorders Reports February 6, 2021
- Toxicity of ayahuasca after 28 days daily exposure and effects on monoamines and brain-derived neurotrophic factor (BDNF) in brain of Wistar rats Metabolic Brain Disease February 27, 2020
- A Single Administration of Psilocybin Persistently Rescues Cognitive Deficits Caused by Adolescent Chronic Restraint Stress Without Long-Term Changes in Synaptic Protein Gene Expression in a Rat Experimental System with Translational Relevance to Depression. Psychedelic Medicine March 1, 2023
and 8 more in the library
Cites 20
- 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 15 more in the library