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de Araujo, D. B.

Publications and source records attributed to de Araujo, D. B..

7 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↗
bioRxiv2022

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain's Neurotransmitter Landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brains rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brains functional architecture.

neuroscience↗
bioRxiv2019

d-Lysergic acid diethylamide has major potential as a cognitive enhancer

Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains uncharted. Here we show that a single dose of d-LSD, a potent serotonergic agonist, increased novel object preference in young and adult rats several days after treatment. d-LSD alone did not increase preference in old animals, but could rescue it to young levels when followed by a 6-day exposure to enriched environment (EE). Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions, with alterations of long-range synapses. Better pattern separation within EE explained its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.

neuroscience↗
bioRxiv2017

Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

Dimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca, Virola) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention, self-referential thought, and internal mentation. Historical and technical restrictions impaired understanding how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by dimethyltryptamine (5-methoxy-N, N-dimethyltryptamine, 5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico systems biology analyses support 5-MeO-DMTs anti-inflammatory effects and reveal a modulation of proteins associated with the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. Proteins involved in long-term potentiation were modulated in a complex manner, with significant increases in the levels of NMDAR, CaMKII and CREB, but a reduction of PKA and PKC levels. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.

neuroscience↗
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↗