This case-control fMRI study (n=38 males) found that long-term ayahuasca users showed significantly higher psychological resilience scores and altered emotional brain reactivity patterns compared to controls. Machine learning algorithms achieved 75% accuracy in distinguishing users from non-users.
Abstract of Resilience and Brain Changes in Long-Term Ayahuasca Users
“Background: Ayahuasca is an Amazonian psychedelic brew that contains dimethyltryptamine (DMT) and beta carbolines. Prolonged use has shown changes in cognitive-behavioral tasks, and in humans, there is evidence of changes in cortical thickness and an increase in neuroplasticity factors that could lead to modifications in functional neural circuits.
Purpose: To investigate the long-term effects of Ayahuasca usage through psychometric scales and fMRI data related to emotional processing using artificial intelligence tools.
Study Type: Retrospective Cross-sectional, case–control study.
Subjects: 38 healthy male participants (19 long-term Ayahuasca users and 19 non-user controls).
Field Strength/Sequence: 1.5 Tesla; gradient-echo T2*-weighted echo-planar imaging sequence during an implicit emotion processing task.
Assessment: Participants completed standardized psychometric scales including the Ego Resilience Scale (ER89). During fMRI, participants performed a gender judgment task using faces with neutral or aversive (disgust/fear) expressions. Whole-brain fMRI data were analyzed using multivariate pattern recognition.
Statistical Tests: Group comparisons of psychometric scores were performed using Student’s t-tests or Mann–Whitney U tests based on normality. Multivariate pattern classification and regression were performed using machine learning algorithms: Multiple Kernel Learning (MKL), Support Vector Machine (SVM), and Gaussian Process Classification/Regression (GPC/GPR), with k-fold cross-validation and permutation testing (n = 100–1000) to assess model significance (α = 0.05).
Results: Ayahuasca users (mean = 43.89; SD = 5.64) showed significantly higher resilience scores compared to controls (mean = 39.05; SD = 5.34). The MKL classifier distinguished users from controls with 75% accuracy (p = 0.005). The GPR model significantly predicted individual resilience scores (r = 0.69).
Data Conclusion: Long-term Ayahuasca use may be associated with altered emotional brain reactivity and increased psychological resilience. These findings support a neural patterns consistent with long-term adaptations of Ayahuasca detectable via fMRI and machine learning-based pattern analysis.“
Authors: Lucas Rego Ramos, Orlando Fernandes Jr & Tiago Arruda Sanchez
Summary of Resilience and Brain Changes in Long-Term Ayahuasca Users
The study opens by highlighting the long-standing use of psychoactive plants in many civilisations, with ayahuasca presented as one of the most widely used psychedelic brews in Brazil and beyond. Traditionally consumed in indigenous and syncretic religious rituals, ayahuasca is prepared by combining two plants: Psychotria viridis, which contains the psychedelic compound DMT (dimethyltryptamine), and Banisteriopsis caapi, which contains beta-carboline alkaloids such as harmine and tetrahydroharmine. These compounds act synergistically; while DMT activates serotonin 5-HT2A receptors in the brain, the alkaloids inhibit enzymes known as monoamine oxidases (MAO), which would otherwise rapidly break down DMT. This pharmacological combination allows DMT to become active when ingested orally.
The introduction explains that scientific interest in ayahuasca has increased, with recent clinical trials and laboratory studies showing its potential in psychiatric disorders. For example, earlier research demonstrated that ayahuasca boosts brain-derived neurotrophic factor (BDNF), a protein that supports the survival of neurons and promotes neurogenesis. It also influences the sigma-1 receptor, which contributes to stress regulation, neuroprotection, and brain plasticity. Short-term use of ayahuasca has been associated with altered mood, changes in cognition, and heightened emotional reactivity. Neuroimaging studies reveal acute effects on the brain’s default mode network and increased blood flow in emotional processing regions, including the amygdala and insula.
The authors note that machine learning is increasingly used in neuroscience to detect subtle brain changes induced by psychoactive substances. For example, machine learning has helped predict treatment outcomes with psilocybin in depression and distinguish LSD from placebo conditions in imaging studies. Unlike traditional methods, these techniques can identify specific brain patterns related to drug effects. However, few studies have applied these advanced analyses to psychedelics in the long term. The authors therefore aimed to explore whether long-term ayahuasca use, independent of acute intoxication, produces measurable differences in brain function and psychological resilience. They hypothesised that extended use might alter how the brain processes emotions, especially in the limbic and prefrontal regions involved in emotional regulation.
Materials and Methods
Sample Characteristics
Find this paper
https://doi.org/10.1002/jmri.70063
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Cite this paper (APA)
Ramos, L. R., Fernandes Jr, O., & Sanchez, T. A. (2025). Resilience and Brain Changes in Long‐Term Ayahuasca Users: Insights From Psychometric and fMRI Pattern Recognition. Journal of Magnetic Resonance Imaging.
Study details
Compounds studied
Ayahuasca
Topics studied
Healthy Subjects
Neuroscience
Study characteristics
Observational
Bio/Neuro
Participants
38
Humans