Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

This randomized placebo-controlled trial investigated the antidepressant efficacy of ayahuasca (25.2mg/70kg DMT, 130.2mg/70kg harmine, 16.8mg/70kg harmaline, 84mg/70kg tetrahydroharmine) in patients with depression. While both groups exhibited improvements in depression, between-group effect sizes increased throughout the week, yielding a significantly higher response rate in the ayahuasca group after a week.

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.”

Authors: Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias, Katia C. Andrade, Morgana M. Novaes, Jessica A. Pessoa, Sergio A. Mota-Rolim, Flávia L. Osório, Rafael Sanches, Rafael G. dos Santos, Luís Fernando Tófoli, Gabriela de Oliveira Silveira, Mauricio Yonamine, Jordi Riba, Francisco R. Santos, Antonio A. Silva-Junior, João C. Alchieri, Nicole L. Galvão-Coelho, Bruno Lobão-Soares, Jaime E. C. Hallak, Emerson Arcoverde, João P. Maia-de-Oliveira & Dráulio B. Araújo

Notes

This paper is included in our ‘Top 10 Articles on Psychedelics in the Treatment of Depression‘

This paper is included in the meta-analytical review by Galvão-Coelho and colleagues (2021) that found psychedelics to improve mood (for those with mood disorders) both in the short and long-term (up to 60 days).

Summary