Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial
Raíssa Nóbrega de Almeida, Ana Cecília de Menezes Galvão, Flávia Santos Da Silva, Erick Allan Dos Santos Silva, Fernanda Palhano-Fontes, João Paulo Maia‐de‐oliveira, Dráulio Barros de Araújo, Bruno Lobão‐soares, Nicole Leite Galvão‐coelho
Frontiers in Psychology June 4, 2019 DOI: 10.3389/fpsyg.2019.01234 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind randomized placebo-controlled clinical trial Peer reviewed |
|---|---|
| Sample size | 73 |
| Population | Healthy controls and patients with treatment-resistant depression |
| Intervention | Ayahuasca |
| Dose | single dose |
| Duration | 48 hours |
| Topics | Ayahuasca Serotonin |
| Keywords | Brain-derived neurotrophic factor Placebo Antidepressant Neurotrophic factors Depression economics Randomized controlled trial Oncology Endocrinology Receptor Hippocampus Pathology |
| Citations | 173 |
| Registration | NCT02914769 |
| Key findings | Ayahuasca increased serum BDNF levels at 48 hours compared with placebo, and in patients this increase correlated with reduced depressive symptoms. |
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).
Comparable studies
Other randomized controlled trials on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Patients with treatment-resistant depression | 2018 | Randomized controlled trial | n = 29 |
| Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Volunteers with prior experience in the use of psychedelics | 2003 | Double-blind placebo-controlled clinical trial | n = 18 |
| Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers Healthy male volunteers with prior experience using ayahuasca | 2001 | Single-blind crossover placebo-controlled clinical trial | n = 6 |
| Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant Male volunteers with prior experience in the use of psychedelics | 2006 | Randomized controlled trial | n = 15 |
| Human brain effects of DMT assessed via EEG-fMRI. Healthy volunteers | 2023 | Within-subjects, placebo-controlled design | n = 20 |
Citations in the library
Cited by 141
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry September 10, 2021
- Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology October 15, 2020
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology February 25, 2022
and 136 more in the library
Cites 27
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
and 22 more in the library