Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca
In a double‑blind placebo‑controlled trial of treatment‑resistant depression patients and healthy controls, ayahuasca produced a significant 48‑hour reduction in C‑reactive protein (CRP) and, in patients, larger CRP decreases correlated with greater reductions in depressive symptoms. No significant effects were seen for interleukin‑6 or BDNF, and these biomarkers did not predict antidepressant response or remission.
Authors
- Fernanda Palhano-Fontes
- Nathalia Galvão-Coelho
- Daniel Perkins
Published
Abstract
Background
Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients ( n = 28) and healthy controls ( n = 45).
Aims
We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale.
Results
At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed ( rho = –0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation ( rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed.
Conclusions
These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.
Research Summary of 'Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca'
Introduction
Major depressive disorder (MDD) is heterogeneous and many patients do not achieve sustained remission with standard pharmacological treatments, leaving a subset with treatment-resistant depression. Earlier research has identified raised circulating inflammatory markers in some people with depression, notably interleukin 6 (IL-6) and C-reactive protein (CRP), and has linked chronic stress, reduced brain-derived neurotrophic factor (BDNF), and inflammation to depressive pathophysiology. Findings on whether conventional antidepressants reduce inflammatory markers are inconsistent, and baseline inflammation may influence treatment effects. Classical serotonergic psychedelics have attracted renewed interest as potentially fast-acting antidepressants, and some preclinical and mechanistic work has proposed direct anti-inflammatory actions mediated via 5-HT2A and sigma-1 (σ1R) receptors. Leite Galvão‑Coelho and colleagues set out to examine whether a single dose of ayahuasca alters blood inflammatory biomarkers and whether such changes relate to antidepressant effects. Using data from a randomised, double-blind, placebo-controlled trial in adults with treatment-resistant depression and healthy controls, the investigators measured plasma CRP and serum IL-6 before treatment and 48 hours after dosing, and tested correlations with serum cortisol and BDNF as well as associations with clinical change on the Montgomery-Åsberg Depression Rating Scale (MADRS). They hypothesised that changes in inflammatory markers would correlate with symptom improvement and might predict antidepressant response or remission at 48 hours.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Galvão-Coelho, N. L., de Menezes Galvão, A. C., de Almeida, R. N., Palhano-Fontes, F., Campos Braga, I., Lobão Soares, B., Maia-de-Oliveira, J. P., Perkins, D., Sarris, J., & de Araujo, D. B. (2020). Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. Journal of Psychopharmacology, 34(10), 1125-1133. https://doi.org/10.1177/0269881120936486
References (10)
Papers cited by this study that are also in Blossom
Galvão-Coelho, N. L., de Almeida, R. N., de Menezes Galvão, A. C. et al. · Frontiers in Psychology (2019)
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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)
Szabo, A., Kovacs, A., Frecska, E. et al. · PLOS ONE (2014)
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