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Psychol Med. 2019 Mar;49(4):655-663. doi: 10.1017/S0033291718001356. Epub 2018 Jun 15.

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

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Brain Institute, Federal University of Rio Grande do Norte (UFRN),Natal/RN,Brazil.
Onofre Lopes University Hospital, UFRN,Natal/RN,Brazil.
Department of Neurosciences and Behaviour,University of São Paulo (USP),Ribeirão Preto/SP,Brazil.
Department of Medical Psychology and Psychiatry,University of Campinas,Campinas/SP,Brazil.
Department of Clinical Analysis and Toxicology,USP,São Paulo/SP,Brazil.
Sant Pau Institute of Biomedical Research,Barcelona,Spain.
Department of Pharmacy,UFRN,Natal/RN, -Brazil.
Department of Psychology,UFRN,Natal/RN,Brazil.
National Institute of Science and Technology in Translational Medicine (INCT-TM),Ribeirão Preto/SP,Brazil.



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 (NCT02914769).


Ayahuasca; HRS; MEQ; depression; psychedelics; randomized controlled trial (RCT)

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