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Differential effects of subacute ayahuasca administration on CA1 and CA3 hippocampal layer thickness in C57BL/6 mice

Otávio Durigon Cocco, Marina Rodrigues da Silva, Gabriel Fernandes Gonçalves, Luana Tenório Lopes, Luciane Helena Gargaglioni Batalhão, Marcelo Leite da Veiga, Isabela Maraschin Vieira

ANPAbstract_CBN26 October 7, 2026 DOI: 10.65034/anpabstract_cbn260108 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled animal experiment Peer reviewed
Population Adult male C57BL/6 mice, 10–12 weeks old
Intervention Ayahuasca
Dose 0.1 mL/day
Duration Four consecutive days of administration; tissue collected 24 hours after the last dose
Topics Ayahuasca
Key findings Subacute oral Ayahuasca administration in mice was associated with a significant reduction in CA1 hippocampal thickness (mean 42.645 µm vs 50.844 µm in controls) but no significant change in CA3 thickness (67.780 µm vs 70.336 µm). The authors suggest this indicates region-specific structural effects, possibly reflecting short-term tissue reorganization.

Abstract

Background: The hippocampus is a key structure for memory and neuronal integration, comprising subregions with distinct morphological and functional properties. Among them, CA1 and CA3 display specific organizational features: CA1 is highly plastic and commonly used as a marker of morphophysiological changes associated with cognition, whereas CA3 is characterized by recurrent circuits and high synaptic integration capacity, making both regions relevant targets for neural plasticity studies. Ayahuasca, a traditional Amazonian psychoactive brew, has been associated with neuroplastic effects; however, its impact on hippocampal cytoarchitecture remains poorly understood.

Objective: This study aimed to evaluate the effect of subacute Ayahuasca administration on the thickness of the CA1 and CA3 hippocampal regions in C57BL/6 mice.

Methods: Adult male mice (10–12 weeks) were allocated into two groups: Vehicle (filtered water) and Ayahuasca (0.1 mL/day), administered orally for four consecutive days. Twenty‑four hours after the last administration, animals were anesthetized with isoflurane and transcardially perfused with buffered paraformaldehyde. Brains were collected, fixed, processed for paraffin embedding, sectioned on a microtome, and stained with hematoxylin and eosin. The thickness of CA1 and CA3 was quantified by morphometry using ImageJ software.

Results: In CA1, vehicle‑treated animals presented a mean thickness of 50.844 ± 11.727 µm (median 50.038 µm), whereas the Ayahuasca group showed 42.645 ± 8.908 µm (median 41.966 µm), with a statistically significant reduction in thickness in Ayahuasca‑treated animals compared with controls (Mann–Whitney test, p < 0.0001). In contrast, no significant differences were observed in CA3 thickness: the vehicle group showed a mean of 70.336 ± 17.871 µm (median 67.514 µm), while the Ayahuasca group presented 67.780 ± 20.079 µm (median 65.300 µm), with no statistically significant difference between groups (Mann–Whitney test, p = 0.2017).

Conclusion: These findings indicate that subacute Ayahuasca exposure induces region‑specific structural effects within the hippocampus, promoting a reduction in CA1 layer thickness while preserving CA3 thickness. The decrease in CA1 thickness may reflect tissue reorganization involving changes in cellular organization and/or extracellular matrix architecture, suggesting short‑term modulation of hippocampal structure by Ayahuasca. Taken together, the results support a selective morphostructural susceptibility of CA1, highlighting the importance of hippocampal subregional analysis for understanding the neurobiological effects of Ayahuasca on the central nervous system.

Comparable studies

Other preclinical and animal studies on ayahuasca, most cited first.

Study Year Design Participants
Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Eight ayahuasca samples from Peru and several Banisteriopsis caapi cultivars 1984 Qualitative and quantitative chemical analysis with in vitro assay
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains 2017 In vitro experimental study
N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice 2020 In vitro and in vivo experimental study
Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat Female Wistar rats 2015 Observational cohort
Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Mice 2015 Experimental study

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