OPEN Foundation

B. Lobao-Soares

Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca

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.

Galvão-Coelho, N. L., de Menezes Galvão, A. C., de Almeida, R. N., Palhano-Fontes, F., Campos Braga, I., Lobão Soares, B., … & de Araujo, D. B. (2020). Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. Journal of Psychopharmacology34(10), 1125-1133; 10.1177/0269881120936486
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It’s Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

Abstract

Ayahuasca is a psychoactive brew traditionally used in shamanistic and vegetalistic rituals and has recently received lot of attention due to potential cognitive benefits. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The present study approaches the effects of chronic and acute exposure to two Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to discriminate objects in a one-trial learning task in zebrafish. Based on the combination of concentrations and exposure regimens, we divided adult zebrafish in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and control 0.0 (n = 20 for each group). Then we tested them in a memory task of object discrimination. Acute Ayahuasca exposed groups performed similarly to the control group, however chronically treated fish (13 days) presented both impaired discriminative performance and locomotor alterations. Overall, these results indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure, negatively affects mnemonic parameters in zebrafish. In single exposure it does not affects cognitive performance, but the higher concentration (0.5) affected locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral pharmacological studies of drug screening, in special to psychedelic drug research.

Eduardo-da-Silva, P., Lobao-Soares, B., Amarilha, H., Pinheiro-da-Silva, J., Silva, P. F., & Luchiari, A. C. (2018). It’s tea time: Interference of Ayahuasca brew on discriminative learning in zebrafish. Frontiers in behavioral neuroscience12, 190., 10.3389/fnbeh.2018.00190

Link to full text

It's Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

Abstract

Ayahuasca is a psychoactive brew traditionally used in shamanistic and vegetalistic rituals and has recently received lot of attention due to potential cognitive benefits. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The present study approaches the effects of chronic and acute exposure to two Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to discriminate objects in a one-trial learning task in zebrafish. Based on the combination of concentrations and exposure regimens, we divided adult zebrafish in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and control 0.0 (n = 20 for each group). Then we tested them in a memory task of object discrimination. Acute Ayahuasca exposed groups performed similarly to the control group, however chronically treated fish (13 days) presented both impaired discriminative performance and locomotor alterations. Overall, these results indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure, negatively affects mnemonic parameters in zebrafish. In single exposure it does not affects cognitive performance, but the higher concentration (0.5) affected locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral pharmacological studies of drug screening, in special to psychedelic drug research.

Eduardo-da-Silva, P., Lobao-Soares, B., Amarilha, H., Pinheiro-da-Silva, J., Silva, P. F., & Luchiari, A. C. (2018). It’s tea time: Interference of Ayahuasca brew on discriminative learning in zebrafish. Frontiers in behavioral neuroscience12, 190., 10.3389/fnbeh.2018.00190

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Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish

Abstract

The combined infusion of Banisteriopsis caapi stem and Psychotria viridis leaves, known as ayahuasca, has been used for centuries by indigenous tribes. The infusion is rich in NN-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, with properties similar to those of serotonin. Despite substantial progress in the development of new drugs to treat anxiety and depression, current treatments have several limitations. Alternative drugs, such as ayahuasca, may shed light on these disorders. Here, we present time-course behavioral changes induced by ayahuasca in zebrafish, as first step toward establishing an ideal concentration for pre-clinical evaluations. We exposed adult zebrafish to five concentrations of the ayahuasca infusion: 0 (control), 0.1, 0.5, 1, and 3 ml/L (n = 14 each group), and behavior was recorded for 60 min. We evaluated swimming speed, distance traveled, freezing and bottom dwelling every min for 60 min. Swimming speed and distance traveled decreased with an increase in ayahuasca concentration while freezing increased with 1 and 3 ml/L. Bottom dwelling increased with 1 and 3 ml/L, but declined with 0.1 ml/L. Our data suggest that small amounts of ayahuasca do not affect locomotion and reduce anxiety-like behavior in zebrafish, while increased doses of the drug lead to crescent anxiogenic effects. We conclude that the temporal analysis of zebrafish behavior is a sensitive method for the study of ayahuasca-induced functional changes in the vertebrate brain.
Savoldi, R., Polari, D., Pinheiro-da-Silva, J., Silva, P. F., Lobao-Soares, B., Yonamine, M., … & Luchiari, A. C. (2017). Behavioral changes over time following ayahuasca exposure in zebrafish. Frontiers in behavioral neuroscience11. 10.3389/fnbeh.2017.00139
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