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).
Highlights
There has been some recent debate about the efficacy of currently available antidepressants (Cipriani et al, 2018; Hengartner and Plöderl, 2018)
We found that volunteers treated with ayahuasca (n = 35; μ = 1179.81 ± 652.21 pg/mL; 95% CI: 10824.21–13149.12) had higher levels of brainderived neurotrophic factor (BDNF) at 48 h after the dosing session (D2) than those treated with placebo (n = 34; μ = 10229.54 ± 633.58 pg/mL; 95% CI: 9452.28– 11800.33) (GLM; Treatment: F = 4.81, df = 1, p = 0.03)
We found an interaction between serum BDNF and serum cortisol levels at baseline
Summary
There has been some recent debate about the efficacy of currently available antidepressants (Cipriani et al, 2018; Hengartner and Plöderl, 2018). It has been suggested that harmine increases BDNF in the hippocampus of rodent animal models after treatment (Fortunato et al, 2010; Brierley and Davidson, 2012) Taking these evidences into account, we hypothesize that BDNF plays a direct role in the neuroplasticity observed for different ayahuasca compounds. Preclinical and clinical evidence suggest that patients with depression tend to present lower levels of serum BDNF when compared to healthy individuals (Wilkinson et al, 2018; Ma et al, 2019), which may be reversed after antidepressant drug treatment (Brunoni et al, 2017; Molendijk et al, 2018). This study investigated serum BDNF levels from a randomized placebo-controlled trial that tested the potential antidepressant effect of a single dose of ayahuasca in treatmentresistant depression (Palhano-Fontes et al, 2018). We hypothesize that volunteers treated with ayahuasca could present higher levels of serum BDNF than those treated with placebo and this BDNF levels would predict the improvements observed in depression severity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
