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. 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. 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, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. 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. 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. 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. 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. Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. 7Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.6Department of Clinical Medicine, Federal University of Rio Grande do Norte, Natal, Brazil.5National Science and Technology Institute for Translational Medicine (INCT-TM), Natal, Brazil.
Raíssa Nóbrega de Almeida 1,2, Ana Cecília de Menezes Galvão 1,2, Flávia Santos da Silva 1,2, Erick Allan dos Santos Silva 1, Fernanda Palhano-Fontes 3,4, João Paulo Maia-de-Oliveira 3,5,6, Dráulio Barros de Araújo 3,4, Bruno Lobão-Soares 5,7 and Nicole Leite Galvão-Coelho 1,2,5*
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