Psychological Medicine
June 15, 2018
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Scientific Reports
August 1, 2017
Aline Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
154 citations
The entropic brain hypothesis suggests that psychedelic experiences arise from increased randomness in the brain's functional connectivity. Analyzing resting-state fMRI data from human subjects before and after ingesting ayahuasca, a psychedelic beverage used in Amazonian religious and scientific contexts, researchers found that the Shannon entropy of the brain's degree distribution increased, indicating greater disorder in network connections. Local integration within brain networks increased while global integration decreased. These findings align with the entropic brain hypothesis and relate to users' reports of 'mind-expansion.'
Frontiers in Psychiatry
May 8, 2018
Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida, Erick Allan Dos Santos Silva et al.
102 citations
In treatment-resistant depression, a single dose of ayahuasca normalizes the blunted awakening salivary cortisol response observed in patients, bringing it to levels similar to those in healthy controls. During the dosing session, both patients and healthy volunteers who received ayahuasca showed higher increases in salivary cortisol than those who received placebo. No significant changes in plasma cortisol were detected 48 hours after dosing. These findings suggest that ayahuasca modulates salivary cortisol, a hormone involved in depression's etiology, and support further investigation into its antidepressant potential.
Entropy
January 30, 2019
Aline Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
37 citations
A new network metric, geodesic entropy, measures the Shannon entropy of distances from one node to all others in a network, characterizing how much influence a node has based on the overall network structure. Applied to resting-state functional brain networks of humans, the metric differentiates ordinary consciousness from the altered state induced by Ayahuasca ingestion. On average, functional networks from subjects in the altered state show larger geodesic entropy than those in the ordinary state, suggesting the metric can reveal differences in brain network organization across states of consciousness.
bioRxiv (Cold Spring Harbor Laboratory)
January 27, 2017
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
22 citations
preprint
A single dose of ayahuasca produced significant antidepressant effects in patients with treatment-resistant depression compared to placebo. Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), was significantly lower in the ayahuasca group at one, two, and seven days after dosing. Effect sizes increased over time, reaching a Cohen's d of 1.49 at day seven. Response rates were significantly higher in the ayahuasca group at day seven (64% vs. 27%), and remission rates were marginally significant (36% vs. 7%). This controlled trial supports the safety and therapeutic value of ayahuasca in treating depression.
bioRxiv (Cold Spring Harbor Laboratory)
January 31, 2018
Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida, Erick Allan Dos Santos Silva et al.
5 citations
preprint
In treatment-resistant depression, a single dose of ayahuasca normalizes the blunted awakening salivary cortisol response that is characteristic of the disorder. Patients with major depression showed hypocortisolemia and a diminished cortisol awakening response compared with healthy controls at baseline. During the dosing session, both patients and controls who ingested ayahuasca had a large increase in salivary cortisol relative to placebo groups. Forty-eight hours after ayahuasca, the awakening cortisol response in treated patients became similar to that of controls, an effect not seen with placebo. No changes in plasma cortisol occurred 48 hours after either ayahuasca or placebo. The modulation of salivary cortisol may contribute to ayahuasca's rapid antidepressant effects.
Journal of Physics Complexity
March 1, 2023
Aline Viol, G. M. Viswanathan, Oleksandra Soldatkina et al.
4 citations
The physical basis of consciousness is a central open question in science. This work compares resting-state functional brain networks of individuals before and after ingesting the psychedelic brew Ayahuasca. Using a measure called pairwise information parity, which quantifies statistical symmetries between brain region connections across the entire network, the authors found an increase in average information parity under psychedelic influence. Notably, information parity between regions of the limbic system and frontal cortex was consistently higher for all individuals while under the influence. These findings suggest that the resemblance of statistical influences between pairs of brain region activities tends to increase under Ayahuasca, possibly as a mechanism to maintain network functional resilience.
Chaos Solitons & Fractals
May 30, 2026
Tales Ramos Monteiro Dos Santos, Dráulio B. Araújo, Helcio Felippe et al.
Psychedelic states can help researchers understand how the brain reorganizes at a large scale. In nine people scanned before and after taking ayahuasca, topological data analysis of resting-state fMRI connectivity showed a nominal decrease in persistent entropy of H2 features—a measure of higher-dimensional topological structure—that did not survive correction for multiple comparisons and was not reproduced with signed correlations. Exploratory analyses of signal complexity found descriptive but non-significant increases. These preliminary, hypothesis-generating results highlight persistent homology as a potential framework for studying psychedelic-related brain changes, but replication in larger placebo-controlled studies is needed.
arXiv Preprint Archive
July 28, 2022
Aline Viol, Gandhi M. Viswanathan, Oleksandra Soldatkina et al.
The physical basis of consciousness remains an open question. Using complex network theory, the study compared resting-state functional brain networks of individuals before and after ingesting the psychedelic brew Ayahuasca. The researchers calculated pairwise information parity to quantify statistical symmetries between brain region connectivity across the entire network. They detected an increase in average information parity in brain networks under psychedelic influence. Notably, information parity between regions of the limbic system and frontal cortex was consistently higher for all individuals while under the influence.
arXiv Preprint Archive
September 26, 2018
A. Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
A new network metric called geodesic entropy quantifies the Shannon entropy of the distance distribution from each node to all others, capturing the structural role of individual nodes in a network. Applied to functional brain networks of humans in two states of consciousness—ordinary waking and after ingestion of Ayahuasca—the metric distinguished the states. Brain networks under Ayahuasca showed, on average, larger geodesic entropy than those in the ordinary waking state. The authors suggest geodesic entropy is a useful tool for analyzing complex networks and may improve understanding of emergent behaviors such as self-organized criticality.
arXiv Preprint Archive
November 1, 2016
A. Viol, Fernanda Palhano-Fontes, Heloisa Onias et al.
Psychedelic Ayahuasca increases brain network complexity, supporting ancient wisdom about "mind expansion" with modern neuroscience. Brain scans revealed that this Amazonian brew creates more diverse neural connections while strengthening local brain networks. The changes in brain organization showed higher Shannon entropy, indicating more dynamic and flexible thought patterns during the psychedelic experience.