Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial

Raíssa Nóbrega De Almeida; Ana Cecília de Menezes Galvão; Flavia Santos Da Silva; Erick Allan dos Santos Silva; Fernanda Palhano-Fontes; João Paulo Maia-de-Oliveira; Dráulio Barros de Araújo; Bruno Lobão-Soares; Nicole Leite Galvão-Coelho

doi:10.3389/fpsyg.2019.01234

Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial

Raíssa Nóbrega De Almeida, Ana Cecília de Menezes Galvão, Flavia Santos Da Silva, Erick Allan dos Santos Silva, Fernanda Palhano-Fontes, João Paulo Maia-de-Oliveira, Dráulio Barros de Araújo, Bruno Lobão-Soares, Nicole Leite Galvão-Coelho

Western Sydney University

Research output: Contribution to journal › Article › peer-review

118 Citations (Scopus)

Abstract

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

Original language	English
Article number	1234
Number of pages	13
Journal	Frontiers in Psychology
Volume	10
DOIs	https://doi.org/10.3389/fpsyg.2019.01234
Publication status	Published - 2019

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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De Almeida, R. N., Galvão, A. C. D. M., Da Silva, F. S., Silva, E. A. D. S., Palhano-Fontes, F., Maia-de-Oliveira, J. P., de Araújo, D. B., Lobão-Soares, B., & Galvão-Coelho, N. L. (2019). Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial. Frontiers in Psychology, 10, Article 1234. https://doi.org/10.3389/fpsyg.2019.01234

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title = "Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial",

abstract = "Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).",

author = "{De Almeida}, {Ra{\'i}ssa N{\'o}brega} and Galv{\~a}o, {Ana Cec{\'i}lia de Menezes} and {Da Silva}, {Flavia Santos} and Silva, {Erick Allan dos Santos} and Fernanda Palhano-Fontes and Maia-de-Oliveira, {Jo{\~a}o Paulo} and {de Ara{\'u}jo}, {Dr{\'a}ulio Barros} and Bruno Lob{\~a}o-Soares and Galv{\~a}o-Coelho, {Nicole Leite}",

year = "2019",

doi = "10.3389/fpsyg.2019.01234",

language = "English",

volume = "10",

journal = "Frontiers in Psychology",

issn = "1664-1078",

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De Almeida, RN, Galvão, ACDM, Da Silva, FS, Silva, EADS, Palhano-Fontes, F, Maia-de-Oliveira, JP, de Araújo, DB, Lobão-Soares, B & Galvão-Coelho, NL 2019, 'Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial', Frontiers in Psychology, vol. 10, 1234. https://doi.org/10.3389/fpsyg.2019.01234

TY - JOUR

T1 - Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial

AU - De Almeida, Raíssa Nóbrega

AU - Galvão, Ana Cecília de Menezes

AU - Da Silva, Flavia Santos

AU - Silva, Erick Allan dos Santos

AU - Palhano-Fontes, Fernanda

AU - Maia-de-Oliveira, João Paulo

AU - de Araújo, Dráulio Barros

AU - Lobão-Soares, Bruno

AU - Galvão-Coelho, Nicole Leite

PY - 2019

Y1 - 2019

N2 - Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

AB - Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).

UR - https://hdl.handle.net/1959.7/uws:63668

U2 - 10.3389/fpsyg.2019.01234

DO - 10.3389/fpsyg.2019.01234

M3 - Article

SN - 1664-1078

VL - 10

JO - Frontiers in Psychology

JF - Frontiers in Psychology

M1 - 1234

ER -

Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial

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