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

TLDR

Psychedelics such as ayahuasca have shown promise as fast‑onset antidepressants in treatment‑resistant depression, and this study is the first controlled trial to evaluate such a substance. The study aimed to test the antidepressant effects of a single dose of ayahuasca versus placebo in a double‑blind randomized trial of 29 patients with treatment‑resistant depression. Participants received a single dose of ayahuasca or placebo and were evaluated with the MADRS and Hamilton scales at baseline and on days 1, 2, and 7 post‑dosing. Ayahuasca produced significant, dose‑dependent reductions in depression scores at all time points, with larger effect sizes and higher response rates at day 7 (Cohen’s d = 1.49, 64 % vs 27 % response), and a trend toward higher remission (36 % vs 7 %). The trial is registered at ClinicalTrials.gov (NCT02914769).

Abstract

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.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.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).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).