Toxicity of ayahuasca after 28 days daily exposure and effects on monoamines and brain-derived neurotrophic factor (BDNF) in brain of Wistar rats
Abstract
Ayahuasca is a hallucinogenic beverage that affects the serotonergic system and have therapeutic potential for many diseases and disorders, including depression and drug addiction. The objectives of this study were to evaluate the potential toxic effects of ayahuasca on rats after chronic exposure, and the levels of monoamines, their metabolites and the brain-derived neurotrophic factor (BDNF) in the brain. Female and male rats were treated orally for 28 days with H 2 O (control), fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, or ayahuasca (Aya) at doses of 0.5X, 1X and 2X the ritualistic dose (7 to 10 animals/group). Clinical, hematological and macroscopic results showed that ayahuasca was safe to the rats. Behavior tests conducted one hour after the last treatment showed that male rats from the Aya1 group explored the open field central area less than the control group, and the number of entries in the central area compared to total locomotion was also significantly lower in this group and in the FLX group. The hippocampus was removed for BDNF analysis and the remaining brain was used for monoamine analysis by HPLC-FL. Serotonin levels were significantly higher than control only in the Aya2 female group, while a significant reduction of its metabolite 5-HIAA was observed in the FLX group. Dopamine levels were similar among the experimental groups, but the levels of its metabolite DOPAC increased significantly in the Aya1 and Aya2 groups compared to controls, especially in females, and the DOPAC/dopamine turnover was significantly higher in Aya2 group. The levels of HVA, another dopamine metabolite, did not change with the treatments compared to controls, but HVA/DOPAC ratio was significantly lower in all ayahuasca male groups. Norepinephrine was not detected in any brain sample, and the levels of its metabolite MHPG did not change significantly among the groups. BDNF levels in the hippocampus were significantly higher in the FLX and Aya2 female groups compared to controls when expressed in relation to the total brain weight. The mechanisms involved in the increase in serotonin, dopamine turnover and BDNF levels observed in ayahuasca treated animals should be further investigated in specific brain areas.
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Repeated ayahuasca administration resulted in increased anxiety behavior in male rats treated with the middle dose, 1 h after the last treatment.
“These administration patterns did not change hippocampal BDNF protein levels and resulted in increased anxiety behavior in male rats treated with the middle dose, 1 h after the last treatment (63).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [63]
After 3 h, female rats treated with the high dose of ayahuasca exhibited increased hippocampal BDNF protein levels.
“After 3 h, female rats treated with the high dose exhibited increased hippocampal BDNF protein levels but did not show changed anxiety behavior (63).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [63]
Repeated ayahuasca administration (28 days, 0.5, 1, or 2 times human ritualistic oral dose) did not change hippocampal BDNF protein levels in rats at 1 h after the last treatment.
“These administration patterns did not change hippocampal BDNF protein levels and resulted in increased anxiety behavior in male rats treated with the middle dose, 1 h after the last treatment (63).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [63]
After 3 h, female rats treated with the high dose of ayahuasca did not show changed anxiety behavior.
“After 3 h, female rats treated with the high dose exhibited increased hippocampal BDNF protein levels but did not show changed anxiety behavior (63).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [63]
Male, but not female rats showed increased anxiety behavior directly after prolonged ayahuasca administration.
“which were shown in a preclinical study where male, but not female rats showed increased anxiety behavior directly after prolonged ayahuasca administration (63).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [63]
Cortical bdnf mRNA was upregulated by LSD and ayahuasca.
“Cortical bdnf mRNA was upregulated by LSD and ayahuasca (61, 63).”
From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [63]
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Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation
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Natural psychedelics in the treatment of depression; a review focusing on neurotransmitters
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Psychoactive substances 25H-NBOMe and 25H-NBOH induce antidepressant-like behavior in male rats
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Cortical structural differences following repeated ayahuasca use hold molecular signatures
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The zebrafish for preclinical psilocybin research
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Psilocin fosters neuroplasticity in iPSC-derived human cortical neuronsPreprint
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Psilocin fosters neuroplasticity in iPSC-derived human cortical neuronsPreprint
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The current state of ayahuasca research in animal models: A systematic reviewPreprint
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Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons
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Psilocin fosters neuroplasticity in iPSC-derived human cortical neuronsPreprint
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Medical Use of Cannabinoids and Psychedelic Compounds
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Psilocin fosters neuroplasticity in iPSC-derived human cortical neuronsPreprint
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Ayahuasca, DMT, and Mental Health: A Current Review of Scientific Studies
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- Authors
- Colaço, C. S., Alves, S. S., Nolli, L. M., Pinheiro, W. O., de Oliveira, D. G. R., Santos, B. W. L., Pic-Taylor, A., Mortari, M. R., & Caldas, E. D.
- Affiliations
- Universidade de Brasília (BR)
- ORCID
- Venue
- Metabolic Brain Disease
- Published
- 2020-02-27
- Volume
- 35
- Issue
- 5
- Pages
- 739-751
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- OpenAlex
- W4205947596
- Cited by
- 58
- References
- 58
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 11 · 2023: 14 · 2022: 10 · 2021: 4 · 2020: 6 · 2012: 1
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-10-01)
- Open access
- closed
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação de Apoio à Pesquisa do Distrito Federal (0193.000.913/2015)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ayahuasca, toxicity, chronic oral exposure, monoamines, serotonin, dopamine, norepinephrine, brain-derived neurotrophic factor, hippocampus, 5-hydroxyindoleacetic acid, DOPAC, homovanillic acid, fluoxetine, locomotor activity, sex differences, hallucinogens
- MeSH terms
- Animals, Behavior, Animal, Brain Chemistry, Dopamine, Female, Fluoxetine, Hippocampus, Male, Motor Activity, Serotonin, Biogenic Monoamines, Rats, Wistar, Selective Serotonin Reuptake Inhibitors, Brain-Derived Neurotrophic Factor, Banisteriopsis, Rats
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