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A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression

Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias, Katia C Andrade, Morgana Novaes, Jessica A Pessoa, Sergio A Mota-Rolim, Flavia Osório, Rafael Sanches, Rafael G dos Santos, Luís F Tófoli, Gabriela de Oliveira Silveira, Mauricio Yonamine, Jordi Riba, Francisco RR Santos, Antonio A Silva-Junior, João Alchieri, Nicole L Galvão-Coelho, Bruno Lobão-Soares, Jaime Hallak, Emerson Arcoverde, João P Maia-de-Oliveira, Draulio B Araújo
doi: https://doi.org/10.1101/103531
Fernanda Palhano-Fontes
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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Dayanna Barreto
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
3Dept. of Clinical Medicine, UFRN, Natal, Brazil
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Heloisa Onias
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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Katia C Andrade
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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Morgana Novaes
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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Jessica A Pessoa
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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Sergio A Mota-Rolim
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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Flavia Osório
4Dept. of Neurosciences and Behaviour, University of Sao Paulo (USP), Ribeirão Preto, Brazil
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
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Rafael Sanches
4Dept. of Neurosciences and Behaviour, University of Sao Paulo (USP), Ribeirão Preto, Brazil
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
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Rafael G dos Santos
4Dept. of Neurosciences and Behaviour, University of Sao Paulo (USP), Ribeirão Preto, Brazil
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
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Luís F Tófoli
6Dept. of Psychiatry, University of Campinas, Campinas, Brazil
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Gabriela de Oliveira Silveira
7Dept. of Clinical Analysis and Toxicology, USP, São Paulo, Brazil
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Mauricio Yonamine
7Dept. of Clinical Analysis and Toxicology, USP, São Paulo, Brazil
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Jordi Riba
8Sant Pau Institute of Biomedical Research, Barcelona, Spain
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Francisco RR Santos
9Dept. of Pharmacy, UFRN, Natal, Brazil
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Antonio A Silva-Junior
9Dept. of Pharmacy, UFRN, Natal, Brazil
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João Alchieri
10Dept. of Psychology, UFRN, Natal, Brazil
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Nicole L Galvão-Coelho
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
11Dept. of Physiology, UFRN, Natal, Brazil
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Bruno Lobão-Soares
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
12Dept. of Biophysics and Pharmacology, UFRN, Natal, Brazil
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Jaime Hallak
4Dept. of Neurosciences and Behaviour, University of Sao Paulo (USP), Ribeirão Preto, Brazil
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
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Emerson Arcoverde
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
3Dept. of Clinical Medicine, UFRN, Natal, Brazil
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
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João P Maia-de-Oliveira
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
3Dept. of Clinical Medicine, UFRN, Natal, Brazil
5National Institute of Science and Technology in Translational Medicine (INCT-TM), Brazil
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Draulio B Araújo
1Brain Institute, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
2Onofre Lopes University Hospital, UFRN, Natal, Brazil
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  • For correspondence: draulio@neuro.ufrn.br
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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.

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Posted August 15, 2017.
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A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias, Katia C Andrade, Morgana Novaes, Jessica A Pessoa, Sergio A Mota-Rolim, Flavia Osório, Rafael Sanches, Rafael G dos Santos, Luís F Tófoli, Gabriela de Oliveira Silveira, Mauricio Yonamine, Jordi Riba, Francisco RR Santos, Antonio A Silva-Junior, João Alchieri, Nicole L Galvão-Coelho, Bruno Lobão-Soares, Jaime Hallak, Emerson Arcoverde, João P Maia-de-Oliveira, Draulio B Araújo
bioRxiv 103531; doi: https://doi.org/10.1101/103531
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A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias, Katia C Andrade, Morgana Novaes, Jessica A Pessoa, Sergio A Mota-Rolim, Flavia Osório, Rafael Sanches, Rafael G dos Santos, Luís F Tófoli, Gabriela de Oliveira Silveira, Mauricio Yonamine, Jordi Riba, Francisco RR Santos, Antonio A Silva-Junior, João Alchieri, Nicole L Galvão-Coelho, Bruno Lobão-Soares, Jaime Hallak, Emerson Arcoverde, João P Maia-de-Oliveira, Draulio B Araújo
bioRxiv 103531; doi: https://doi.org/10.1101/103531

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