Clinical Trial ARTICLE
Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca: observation from a randomized controlled trial
- 1Federal University of Rio Grande do Norte, Brazil
- 2Center for Biosciences, Federal University of Rio Grande do Norte, Brazil
- 3Department of Physiology and Behavior, Department of Physiology and Behavior, Center for Biosciences, Federal University of Rio Grande do Norte, Brazil
- 4Department of Physiology and Behavior, Center for Biosciences, Federal University of Rio Grande do Norte, Brazil
- 5Onofre Lopes University Hospital, Brazil
- 6Brain Institute, Federal University of Rio Grande do Norte, Brazil
- 7Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Brazil
- 8Department of Biophysics and Pharmacology, Center for Biosciences, Federal University of Rio Grande do Norte, Brazil
Serotonergic psychedelics are emerging as potential antidepressant treatment tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have shown that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants. However, the exact role of BDNF as a biomarker for diagnostic and treatment of major depression needs to be better explored. In this study, registered at http://clinicaltrials.gov (NCT02914769), we investigated serum BDNF levels in healthy controls (N= 45) and patients with treatment resistant depression (N = 28), before (baseline) and 48 hours after (D2) a single dose of ayahuasca or placebo. We found similar baseline levels of serum BDNF in both patients and healthy individuals. We detected lower levels of BDNF at baseline in a subgroup of subjects who also presented hipocortisolemia, with respect to individuals with eucortisolemia. Moreover, we found a baseline 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). Moreover, in 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 (MADRS scores). Few previous randomized controlled trials have evaluated serum BDNF levels in response to antidepressant treatments and their results are not conclusive. This is the first clinical trial to explore the modulation of BDNF in response to a psychedelic with antidepressant potential, and 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 psychedelic substances in the treatment of resistant depression.
Keywords: ayahuasca, antidepressant, BDNF (brain derived neurotrophic factor), biomarker, Cortisol (serum), psychedelics, treatment-resistance, Depression
Received: 30 Jan 2019;
Accepted: 10 May 2019.
Edited by:Karin G. Coifman, Kent State University, United States
Reviewed by:Lucy J. Troup, Strategic Hub for Psychology, Social Work, Health Behaviours and Addictions, University of the West of Scotland, United Kingdom
Roger C. Ho, National University of Singapore, Singapore
Haiteng Jiang, Carnegie Mellon University, United States
Copyright: © 2019 Almeida, Galvão, Da Silva, Silva, Palhano-Fontes, Maia-de-Oliveira, de Araujo, Lobao-Soares and Galvão-Coelho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 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.
* Correspondence: Prof. Nicole Galvão-Coelho, Federal University of Rio Grande do Norte, Natal, Brazil, firstname.lastname@example.org