Modulação sérica do fator neurotrófico derivado do cérebro (BDNF) pela ayahuasca: contribuições para a depressão maior

Abstract

The Major Depression (MD) reaches about 300 million people of all age, totalizing 5% of the world population. American projections suggest a cumulative incidence of DM of 13.6% among men and 36.1% among women. In addition, about 30% of patients do not respond to treatment. Recently, a double-blind, placebo-controlled randomized clinical trial showed that ayahuasca, a psychedelic tea from Amazonian, induced rapid antidepressant effects in patients with treatment-resistant MD. A clinical response was observed 24 hours after it ingestion, with effects statistically different from placebo 7 days post dose. It is speculated that this antidepressant action is related to increased levels of brain-derived neurotrophic factor (BDNF), polypeptide related to neurogenesis and neuroplasticity. In order to better understand the antidepressant action of ayahuasca, this study investigated the serum levels of BDNF in the same sample of this clinical trial, healthy control volunteers (M = 20, W = 25) and MD patients (M = 7, W = 21), before and 48 hours (D2) after ingestion of a single dose of ayahuasca (AYA) or placebo (PLA), in order to associate possible changes in BDNF with depressive symptoms and serum cortisol. The research was approved by the Ethics Committee in Medical Research of the University Hospital Onofre Lopes (process nº 579.479) and registered as clinical trial no. NCT02914769. All blood collections were performed around 7:00 a.m. in order to reduce circadian variations. Prior to administration of AYA / PLA, we found similar serum BDNF levels between patients (P) and controls (C). However, in baseline we detected lower levels of BDNF in a subgroup of volunteers (P and C) who presented hypocortisolemia (n = 31), compared to those with eucortisolemia (n = 38). Moreover, was observed a negative correlation between BDNF and cortisol in these volunteers with eucortisolemia. After treatment (D2) we observed higher levels of BDNF in volunteers (P and C) who ingested AYA (n = 35) when compared to PLA (n = 34). In addition, only patients treated with AYA (n = 14), and not with PLA (n = 14), had a significant negative correlation between serum BDNF levels and depressive symptoms measured by the Depression Scale of Montgomery-Asberg (MADRS). Few clinical trials evaluated serum BDNF levels in patients in response to antidepressant treatments and their results are inconclusive. This is the first double-blind, randomized, placebo-controlled clinical trial to investigate the relation of BDNF and the clinical response of patients with depression after treatment with psychedelic that shows antidepressant potential. We observed a relationship between BDNF and cortisol that corroborates the current literature. In addition, the results suggest a link between ayahuasca-induced antidepressant effects and serum BDNF. Thus, this study contributes with an emerging view of the use of psychedelic drugs in the treatment of treatment-resistant DM, as well as the relationship between BDNF and the druginduced antidepressant effect for DM treatment.