Biology subjects

Palhano-Fontes, F.

Publications and source records attributed to Palhano-Fontes, F..

4 recordsLinked to original sources

bioRxiv2025

Network Rerouting Under Ayahuasca: Temporally and Hemisphere-Resolved EEG Connectomics

Ayahuasca profoundly alters conscious experience, yet robust, time-resolved EEG markers of its network-level effects remain limited. We combined machine learning with complex-network analysis to quantify how functional connectivity reorganizes across time and hemispheres in resting-state EEG from a randomized, double-blind, placebo-controlled trial including three 5-min sessions: pre-dose (T1), 2 h post-dose (T2), and 4 h post-dose (T3). The cohort consisted of naive ayahuasca users, a population known to exhibit attenuated or more stable acute responses, making the detection of network-level changes particularly challenging. Connectivity was estimated using multiple metrics and sliding windows (10-120 s), and network features were computed and averaged to ensure statistical validity. A representation-selection step identified Spearman correlation and an intermediate temporal scale as optimal, with classification performance peaking at 60-70 s (independent-test AUC and accuracy = 0.93). Linear mixed models revealed a bilateral decrease in eigenvector centrality (weaker hub influence), increased degree heterogeneity in the right hemisphere, and reduced global efficiency in the left. Edge-level analyses localized these effects: Posterior-left connections weakened acutely (lowest at T2), whereas right temporal-central coupling transiently strengthened (highest at T2). Together, these convergent results support a mechanistic summary: as hub-centric short-cuts weaken, communication is increasingly routed through alternative, more distributed--and less efficient--pathways, with a right-lateralized expression at a later time. Methodologically, the window-optimized, hemisphere-resolved, and edge-validated pipeline extends prior EEG work and highlights temporal scale (approximately 60 s) as a biologically meaningful parameter for detecting psychedelic-induced network reorganization.

neuroscience↗

bioRxiv2025

Ayahuasca Shifts Brain Dynamics Toward Higher Entropy: Persistent Elevation of Ising Temperature Correlates with Acute Subjective Effects

Serotonergic psychedelics profoundly alter high-order cognition, emotion, and sensory perception, creating dynamic, unpredictable brain states consistent with the entropic brain hypothesis. Although these acute effects are short-lived, users often experience lasting improvements in emotional and social functioning. Yet, few studies have quantitatively linked subjective experiences to neural dynamics. To bridge this gap, we investigate the acute and subacute effects of ayahuasca using fMRI data and the 2D Ising model, estimating the Ising brain temperature to quantify the shift from ordered to disordered resting state configurations and expose the critical transitions that characterize ayahuasca-induced brain dynamics. To complement our analysis, we investigated cortical functional connectivity changes through graph-theoretical metrics, quantifying how psychedelic ingestion alters functional network architecture in acute and subacute phases. Only the Ising temperature reliably differentiated the subacute phase. Applying a recently developed method that combines cortical connectivity analyses with Graph Neural Networks trained on Ising networks, our results robustly revealed significant Ising temperature increases during the acute (p < 0.001) and subacute (p < 0.05) phases compared with placebo, reflecting heightened brain entropy and a persistent shift toward a more disordered, paramagnetic state. To evaluate longer-term effects, the subacute temperature change correlated linearly with affective scores on the Hallucinogenic Rating Scale (HRS) captured during the acute session (p < 0.01), with HRS scores explaining substantially greater variance in the subacute group (adjusted R2 = 0.58) than in the placebo group (adjusted R2 = -0.05). These observations suggest that ayahuasca elevates system entropy and that the magnitude of lasting functional alterations scales with the intensity of the acute subjective experience.

neuroscience↗

bioRxiv2018

A Single Dose Of Ayahuasca Modulates Salivary Cortisol In Treatment-Resistant Depression

Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized placebo-controlled trial supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients and in healthy volunteers. Subjects received a single dose of ayahuasca or placebo, and both plasma and awakening salivary cortisol response were measured at baseline (before dosing) and 48h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients (DM), both with respect to healthy controls group (C). Salivary cortisol also was measured during dosing session and we observed a large increased for both C and DM that ingested ayahuasca, than placebo groups. After 48h of the dosing session (D2) with ayahuasca, awakening salivary cortisol response (for both sexes) of treated patients became similar to levels detected in controls. This was not observed in patients that ingested placebo. No changes in plasma cortisol were observed after 48 hours of ayahuasca or placebo ingestion for both groups and sexes. Therefore, these findings point to new evidence of modulation of ayahuasca on salivary cortisol levels, as cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes related to etiology of depression, this modulation could be an important part of the antidepressant effects observed with ayahuasca. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.

physiology↗

bioRxiv2017

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomised placebo-controlled trial

Major Depressive Disorder affects about 350 million people worldwide, and about one-third of the patients are considered treatment-resistant. Furthermore, available antidepressants take usually two weeks for the onset of their antidepressant effect. Recent open label trials show that psychedelics, such as ayahuasca and psilocybin, hold promise as fast-onset antidepressants. Although promising, these studies were not controlled for the placebo effect. To address this issue, and to further test the antidepressant effects of ayahuasca, we conducted a parallel arm, double-blind randomised placebo-controlled trial, in patients with treatment-resistant major depression. Thirty-five patients with treatment-resistant major depression received a single dose of ayahuasca or placebo. We measured as primary outcome the change in the Hamilton Depression Rating scale (HAM-D) seven days after the dosing session, and as secondary outcomes the changes in Montgomery-[A]sberg Depression Rating Scale (MADRS), and response rates at one day (D1), two days (D2) and seven days (D7) after dosing, and remission rates at D7. This study is registered with http://clinicaltrials.gov (NCT02914769). We observed robust evidence of rapid antidepressant effects of a single dosing session with ayahuasca when compared to placebo. HAM-D scores at D7 were significantly lower in patients treated with ayahuasca than in those treated with placebo (p=0{middle dot}019; Cohens d=0{middle dot}98). MADRS scores were significantly reduced in the ayahuasca group compared to the placebo group at all endpoints (at D1 and D2, p=0{middle dot}04; at D7, p<0{middle dot}0001). Between-group effect sizes increased from D1 to D7 (D1: Cohens d=0{middle dot}84; D2: Cohens d=0{middle dot}84; D7: Cohens d=1{middle dot}49). Response rates were high for both groups at D1 and D2, and were significantly higher in the ayahuasca group only at D7 (64% vs. 27%; OR = 4{middle dot}95; p = 0{middle dot}04; NNT = 2{middle dot}66). Remission rate was not significantly different between groups. Our study provides new evidence of rapid antidepressant effects of ayahuasca for treatment-resistant major depression.

clinical trials↗