Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial
This placebo-controlled, double-blind randomised trial study (n=73) investigated the impact of BDNF (a protein related to the growth of neurons) on patients with depression who were administrated ayahuasca. The trial results observed a potential link between the changes in serum BDNF levels and the antidepressant effects of ayahuasca and also supported using psychedelics as an antidepressant.
Authors
- Fernanda Palhano-Fontes
- Nathalia Galvão-Coelho
- João Paulo Maia-de-Oliveira
Published
Abstract
Introduction
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.
Methods
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.
Results
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.
Discussion
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).
Research Summary of 'Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial'
Introduction
Serotonergic psychedelics are being investigated as potential rapid-acting antidepressants because they engage monoaminergic and neuroplasticity-related pathways implicated in major depression. Brain-derived neurotrophic factor (BDNF) is a neurotrophin linked to synaptic plasticity and hippocampal/prefrontal structural changes observed in depression, and previous preclinical and clinical work suggests some antidepressants increase serum BDNF. However, the utility of peripheral BDNF as a diagnostic or treatment biomarker remains unclear, and few controlled clinical trials have examined whether psychedelic administration modulates BDNF in depressed patients. Leite Galvão-Coelho and colleagues set out to test whether a single dose of ayahuasca alters serum BDNF and whether baseline BDNF or its change relates to depressive symptoms. Using a randomised, double-blind, placebo-controlled design in treatment-resistant depression and a healthy control group, the study tested (1) whether baseline BDNF discriminates patients from controls and relates to clinical features and cortisol, and (2) whether BDNF measured 48 hours after dosing differs between ayahuasca and placebo and predicts symptom change.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Almeida, R. N. D., Galvão, A. C. D. M., da Silva, F. S., Silva, E. A. D. S., Palhano-Fontes, F., Maia-de-Oliveira, J. P., de Araújo, L. 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. https://doi.org/10.3389/fpsyg.2019.01234
References (19)
Papers cited by this study that are also in Blossom
Anderson, T., Petranker, R., Rosenbaum, D. et al. · Psychopharmacology (2019)
Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)
Dakic, V., De Moraes Maciel, R., Drummond, H. et al. · PeerJ (2016)
Dakic, V., Nascimento, J. M., Sartore, R. C. et al. · Scientific Reports (2017)
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Horák, M., Hasíková, L., Verter, N. et al. · Journal of Psychoactive Drugs (2018)
Johnstad, P. G. · Nordic Studies on Alcohol and Drugs (2018)
Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)
Marek, G. J. · Current Topics in Behavioral Neurosciences (2018)
Morales-García, J. A., de la Fuente Revenga, M., Alonso-Gil, S. et al. · Scientific Reports (2017)
Show all 19 referencesShow fewer
Osório, F. L., Sanches, R. F., Macedo, L. et al. · brazilian Journal of Psychiatry (2015)
Palhano-Fontes, F., Barreto, D., Onias, H. et al. · Psychological Medicine (2018)
Polito, V., Stevenson, R. J. · PLOS ONE (2019)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Sanches, R. F., Osório, F. L., Dos Santos, R. G. et al. · Journal of Clinical Psychopharmacology (2016)
Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · Therapeutic Advances in Psychopharmacology (2016)
da Silva, F. S., Galvão-Coelho, N. L. · brazilian Journal of Psychiatry (2019)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
Winkelman, M. J. · Frontiers in Neuroscience (2017)
Cited By (45)
Papers in Blossom that reference this study
Silva-Costa, N., Pessoa, J. A., Andrade, K. C. et al. · Journal of Psychopharmacology (2025)
Soto-Angona, Ó., Andión, O., Sabucedo, P. et al. · Scientific Reports (2025)
Rego Ramos, L., Fernandes Jr, O., Arruda Sanchez, T. · Journal of Magnetic Resonance Imaging (2025)
Agnorelli, C., Spriggs, M. J., Godfrey, K. et al. · Preprints (2024)
Allen, J., Dames, S., Foldi, C. J. et al. · Molecular Psychiatry (2024)
Mallaroni, P., Mason, N. L., Kloft, L. et al. · Frontiers in Neuroscience (2023)
Wall, M. B., Harding, R., Zafar, R. et al. · Molecular Psychiatry (2023)
Winkelman, M. J., Szabo, A., Frecska, E. · European Neuropsychopharmacology (2023)
Vogt, S. B., Ley, L., Erne, L. et al. · Translational Psychiatry (2023)
Perkins, D., Ruffell, S. G. D., day, K. et al. · Frontiers in Neuroscience (2023)
Show all 45 papersShow fewer
Galvão-Coelho, N. L., De Meiroz Grilo, M. L. P., de Sousa, G. M. et al. · Frontiers in Behavioural Neuroscience (2022)
Perkins, D., Pagni, B. A., Sarris, J. et al. · Frontiers in Pharmacology (2022)
Calder, A. E., Hasler, G. · Neuropsychopharmacology (2022)
van Elk, M., Yaden, D. B. · Neuroscience and Biobehavioral Reviews (2022)
Rossi, G. N., Hallak, J. E., Baker, G. et al. · European Archives of Psychiatry and Clinical Neuroscience (2022)
De Gregorio, D., Inserra, A., Enns, J. P. et al. · Neuropsychopharmacology (2022)
Holze, F., Ley, L., Müller, F. et al. · Neuropsychopharmacology (2022)
Reckweg, J., Uthaug, M. V., Szabo, A. et al. · Journal of Neurochemistry (2022)
Vollenweider, F. X., Smallridge, J. W. · Pharmacopsychiatry (2022)
Barker, S. A. · Psychopharmacology (2022)
Schenberg, E. E., Gerber, K. · Transcultural Psychiatry (2022)
Almeida, C. A. F., Pereira, B. P., Pereira Junior, A. A. et al. · Behavioural Brain Research (2022)
Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)
Olson, D. E. · Journal of Neurochemistry (2021)
Becker, A. M., Holze, F., Grandinett, T. et al. · Clinical Pharmacology and Therapeutics (2021)
Khan, S. I., Carter, G. T., Aggarwal, S. K. et al. · Frontiers in Neuroscience (2021)
Dos Santos, R. G., Osório, F. L., Rocha, J. M. et al. · Journal of Clinical Psychopharmacology (2021)
Bement, W., Banks, M. I., Zahid, Z. et al. · Molecular Biology of the Cell (2021)
Rush, B., Marcus, O., García, S. et al. · Frontiers in Pharmacology (2021)
Romeo, B., Hermand, M., Pétillion, A. et al. · Journal of Psychiatric Research (2021)
Rocha, J. M., Rossi, G. N., de Lima Osório, F. et al. · Journal of Clinical Psychopharmacology (2021)
Dos Santos, R. G., Hallak, J. E., Baker, G. et al. · Journal of Psychopharmacology (2021)
da Silva, M. G., Daros, G. C., de Bitencourt, R. M. · Behavioural Brain Research (2021)
Galvão-Coelho, N. L., Marx, W., Sinclair, J. et al. · Psychopharmacology (2021)
Bouso, J. C., Ona, G., Dos Santos, R. G. et al. · Advances in Experimental Medicine and Biology (2021)
Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)
Kadriu, B., Greenwald, M., Ba et al. · International Journal of Neuropsychopharmacology (2020)
Holze, F., Vizeli, P., Ley, L. et al. · Neuropsychopharmacology (2020)
Thompson, C., Szabo, A. · Immunology Letters (2020)
Hutten, N. R. P. W., Mason, N. L., Dolder, P. C. et al. · ACS Pharmacology and Translational Science (2020)
Galvão-Coelho, N. L., de Menezes Galvão, A. C., de Almeida, R. N. et al. · Journal of Psychopharmacology (2020)
Castellanos, J. P., Woolley, C., Bruno, K. A. et al. · Regional Anesthesia and Pain Medicine (2020)
Mason, N. L., Feilding, A., Ramaekers, J. G. · European Neuropsychopharmacology (2020)
Garcia-Romeu, A., Davis, A. K., Griffiths, R. R. et al. · Frontiers in Psychiatry (2020)
Dos Santos, R. G., Hallak, J. E. · Neuroscience and Biobehavioral Reviews (2020)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.