Sci Rep
July 9, 2025
Stephanie Müller, Federico Cavanna, Laura De la Fuente et al.
2 citations
High doses of psilocybin mushrooms caused people to look more locally at paintings, with less spread in where their eyes fixated, compared with low doses. Psilocybin increased subjective emotional intensity and feelings of flow but did not change how people rated the paintings aesthetically, indicating a separation between perceptual and evaluative parts of aesthetic experience. The gaze changes may stem from altered perception of low-level visual features such as textures, shapes, and colors. The work demonstrates that eye tracking can objectively measure psychedelic effects on behavior in naturalistic settings.
June 4, 2023
Timo Torsten Schmidt, Cyril Costines, Enzo Tagliazucchi et al.
2 citations
preprint
The Altered Xperience Project (AXP) is an open citizen science initiative that systematically collects data on subjective experiences from consciousness-manipulating techniques, including psychoactive substances and non-pharmacological methods. A proof-of-principle dataset (v1.0) includes data collected through May 2022, with most gathered between October 3 and 13, 2022. The dataset covers low, medium, and high doses of alcohol, cannabis, NMDA, and psilocybin. Participants were recruited internationally via social media by the citizen science group El gato y la Caja, and participation was incentivized with an infographic comparing individual data to others. The data is publicly available on the Open Science Framework.
Preprints.org
Enzo Tagliazucchi
2 citations
preprint
Serotonergic psychedelics alter conscious awareness, perception, mood, emotion, and cognition, but their effects resist simple classification like stimulant or sedative. Their defining feature is temporarily inducing an altered state of consciousness. Because only humans can explicitly report conscious experiences, studying these compounds requires non-invasive neuroimaging techniques in healthy subjects. This review examines how neuroimaging has been applied to investigate the neural correlates of altered consciousness caused by serotonergic psychedelics.
Neuroscience and biobehavioral reviews
July 1, 2026
Bruno Moses, Manoj K. Doss, Enzo Tagliazucchi
1 citation
The entropic brain hypothesis suggests that brain entropy—the uncertainty in brain state distributions—increases during psychedelic states and other states of expanded consciousness, while decreasing in states of diminished consciousness. Many neuroimaging studies have reported heightened entropy under psychedelics, leading some to consider entropy a reliable biomarker of the psychedelic state. This paper argues that view is oversimplified. It reviews evidence for entropy metrics, then identifies four challenges: entropy changes are not specific to psychedelics; current methods do not capture multidimensional conscious states; multiple entropy metrics exist with different interpretations and limited consistency; and there is little evidence linking brain entropy directly to phenomenal richness. The authors conclude the concept warrants further investigation and offer suggestions for future research.
PLoS Computational Biology
October 28, 2025
Fernando Lehue, Carlos Coronel‐Oliveros, Vicente Medel et al.
1 citation
During sleep, brain dynamics shift from wakefulness through NREM stages N1, N2, and N3, driven partly by decreases in the neuromodulators acetylcholine (ACh) and noradrenaline (NA). Analyzing fMRI data from healthy individuals and using a whole-brain model, the study shows that functional connectivity (FC) changes distinctly: locus coeruleus connectivity with the cortex decreases during N2 and N3, while basal forebrain connectivity with the cortex decreases during N3. Compared to wakefulness, the brain becomes more integrated in N1 and more segregated in N3. Region-specific neurotransmitter effects are key to explaining these FC changes, advancing understanding of how neurochemistry modulates sleep stages and consciousness transitions.
Neuroscience of Consciousness
January 1, 2025
Stephanie Müller, Federico Cavanna, Laura Alethia de la Fuente et al.
1 citation
Psilocybin alters how people process visual salience during natural scene perception, leading to more focused and exploratory gaze patterns. In a self-blinded study, 23 participants viewed natural scenes under low and high doses of psilocybin while their eye movements were tracked. Under the high dose, fixations concentrated more on salient image regions, inter-fixation distance decreased, and the Shannon entropy of fixations on high-saliency areas indicated more exploratory and less predictable scanning. Resting-state electroencephalography showed broadband spectral power reductions and increased Lempel-Ziv complexity, with delta power negatively correlating with salience metrics. These findings suggest psilocybin shifts attentional dynamics, heightening sensitivity to visual salience and altering gaze behavior.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2024
Jakub Vohryzek, Morten L. Kringelbach, Edmundo Lopez-Sola et al.
1 citation
preprint
Both psychedelic states and reduced states of consciousness flatten the brain's functional hierarchy, yet their behavioral and phenomenological profiles differ. To resolve this paradox, researchers defined hierarchy by the brain's proximity to thermodynamic equilibrium and examined changes induced by three serotonergic psychedelics: psilocybin, LSD, and DMT. All three consistently reduced the functional hierarchy globally. Unlike loss of consciousness, psychedelics moved the brain toward equilibrium while increasing neural activity complexity, indicating a distinct mechanism involving altered configuration and differentiation of resting-state networks. This work demonstrates how statistical mechanics metrics can characterize different global brain states, advancing understanding of consciousness as an emergent collective process.
bioRxiv Preprint Server
December 19, 2024
Evan Lewis-Healey, Carla Pallavicini, Federico Cavanna et al.
1 citation
preprint
A dose of the fast-acting psychedelic DMT rapidly reorganizes conscious experience and brain dynamics, but the link between neural complexity and subjective effects is weaker than previously thought. Nineteen participants received 20 mg or 40 mg of DMT in two sessions. The higher dose produced more extreme visual hallucinations and emotionally intense experiences. Contrary to earlier claims, Lempel-Ziv complexity—a measure of neural signal diversity—was the least strongly associated neural marker of the psychedelic state. The findings suggest the relationship between neural complexity and phenomenology during psychedelic experiences is less clear than originally hypothesized.
bioRxiv (Cold Spring Harbor Laboratory)
February 22, 2022
Camila Sanz, Federico Cavanna, Stephanie Müller et al.
1 citation
preprint
Low doses of psilocybin (microdoses) can be detected in natural speech. In a double-blind, placebo-controlled experiment, participants given 0.5 g of psilocybin mushrooms showed significant differences in verbosity and sentiment scores compared to placebo, though semantic variability did not differ. Machine learning classifiers using these speech metrics distinguished between the psilocybin and placebo conditions with high accuracy (AUC≈0.8). These findings suggest that unconstrained natural language may serve as a practical, low-cost tool for monitoring microdosing effects, addressing limitations of existing questionnaires designed for larger psychedelic doses.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
bioRxiv (Cold Spring Harbor Laboratory)
September 8, 2019
Laura Alethia de la Fuente, Federico Zamberlán, Andrés Sánchez Ferrán et al.
1 citation
preprint
Machine learning analysis of a large public dataset where users freely reported their experiences with cannabis strains, combined with chemical composition data, reveals that cannabis strains can be reliably classified into three major clusters corresponding to Cannabis sativa, Cannabis indica, and hybrids based on self-reported effect and flavor tags. Terpene profiles matched users' perceptual characterizations and could predict associations between different psychoactive effects, while cannabinoid content was variable even within individual strains. The findings suggest that flavor perception, reflecting robustly inherited terpene content, could serve as a reliable marker to predict psychoactive effects, offering a data-driven approach to strain classification for the growing medicinal and recreational cannabis market.
bioRxiv
May 4, 2026
Tomás Ariel D’amelio, Tomás Gil Garbagnoli, Jerónimo Rodríguez Cuello et al.
Inhalation of DMT, a serotonergic psychedelic, produces a brief surge in sympathetic nervous system activity—heart rate, skin conductance, and respiration—that closely tracks the intensity of the emotional experience. Nineteen participants received 20 or 40 mg of DMT under a semi-naturalistic blinded design. Higher doses caused heart rate and breathing to increase within the first two minutes, while skin conductance rose only later, indicating a prolonged autonomic response. As the drug's effects waned, feelings of pleasantness and bliss emerged. Combining simple physiological measures with moment-by-moment self-reports offers a way to objectively characterize psychedelic-induced emotional states, which may aid future clinical biomarker research.
bioRxiv Preprint Server
April 22, 2026
Nicolás Bruno, Federico Cavanna, Federico Zamberlán et al.
preprint
Spontaneous thoughts make up most of everyday inner experience, but studying them is difficult because traditional methods disrupt the natural flow of thinking or introduce motor artifacts. An alternative approach combined delayed verbal retrospective free reports with automated ratings from large language models. Twenty-two participants performed an eyes-closed free-thinking task, and their reports were evaluated on ten dimensions by four LLMs and human raters. Machine-learning models trained on EEG features achieved above-chance accuracy for predicting emotional valence. LLMs showed higher inter-rater agreement than humans, supporting their use for scalable annotation and suggesting that affective dimensions of spontaneous thoughts can be decoded from brain activity.
Apollo (University of Cambridge)
December 30, 2025
Evan Lewis-Healey, Carla Pallavicini, Federico Cavanna et al.
A dose of the fast-acting psychedelic drug DMT rapidly reorganizes both conscious experience and brain activity. In a blinded, counterbalanced study, 19 participants received either 20 mg or 40 mg of freebase DMT. The higher dose caused more extreme visual hallucinations and emotionally intense experiences. Electroencephalography showed that changes in alpha brainwave power and a measure of signal irregularity (permutation entropy) were most strongly linked to moment-by-moment changes in subjective experience. Surprisingly, a measure of neural signal complexity (Lempel-Ziv complexity), previously thought to be a robust marker of psychedelic states, showed the weakest link to experience. This suggests the connection between brain complexity and conscious experience during psychedelic states is less straightforward than previously assumed.
Neuroscience of Consciousness
December 27, 2025
Yayla A Ilksoy, Alethia de la Fuente, Jacobo Sitt et al.
In a backward masking task, participants received transcranial alternating current stimulation (tACS) at 20 Hz or 40 Hz to test whether beta- or gamma-band oscillations causally influence conscious and unconscious visual perception. Contrary to expectations, 20 Hz-tACS selectively impaired objective visibility (correct categorization of masked targets) but not subjective visibility (self-reported conscious perception). 40 Hz-tACS showed no effect. Local beta power increased after 20 Hz-tACS, but inter-areal beta synchrony may have been disrupted. The findings suggest a potential causal role for beta-band activity in visual perception, particularly for objective discrimination, and point to future studies using other stimulation methods or model organisms.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2025
Carla Pallavicini, Lorena Llobenes, Federico Cavanna et al.
Combining psilocybin with a compassion-focused imagery exercise produces long-term synergistic effects on cognitive absorption, self-compassion, and decentering. In a sample of 105 participants, those who received a compassion imagery prime before taking psilocybin showed distinct changes in brain network interactions—particularly among attentional, executive, and default mode networks—compared to those who simply focused on breathing. fMRI-based classifiers could distinguish the two priming conditions only at a high dose of psilocybin. The findings suggest that pairing psilocybin with compassion-based practices may amplify lasting psychological shifts and reorganize large-scale brain networks, though confirmatory studies are needed.
Open Science Framework
January 1, 2025
Federico Cavanna, Enzo Tagliazucchi
Psilocybin acutely alters probabilistic reinforcement learning in healthy adults. In a double-blind, randomized, within-subject, placebo-controlled study, behavioral data and event-related potentials from EEG recordings will reveal how the psychedelic modulates neural mechanisms of reward processing and decision-making.
bioRxiv
January 29, 2024
Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al.
preprint
The brain state induced by psychedelic drugs is often studied as a static snapshot, but this work focuses on the transition itself. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the authors show that the drug briefly pushes the brain near a critical point where it becomes maximally responsive to perturbations. This heightened reactivity is concentrated in fronto-parietal regions and visual cortices and correlates with serotonin 5HT2a receptor density. The findings suggest that even a short psychedelic episode can have a lasting influence because minimal perturbations during this transient achieve maximal effect, with the temporal evolution aligning with the drug's pharmacokinetics.
arXiv (Cornell University)
August 6, 2020
Rodrigo Cofré, Rubén Herzog, Pedro A. M. Mediano et al.
Altered states of consciousness provide a key opportunity to understand how global brain activity changes relate to different subjective experiences. This paper advocates a research program that bridges bottom-up generative models of whole-brain activity with top-down signatures proposed by theories of consciousness. It defines altered states, discusses relevant brain-activity signatures, and introduces whole-brain models to explore the mechanisms of altered consciousness from the bottom-up. The authors argue that systematic investigation of altered states via bottom-up modeling may help clarify the biophysical, informational, and dynamical foundations of consciousness.
bioRxiv Preprint Server
September 28, 2022
Yonatan Sanz Perl, Carla Pallavicini, Juan Piccinini et al.
preprint
Brain states are often described on a single scale from full consciousness to unconsciousness, but this ignores the complex, high-dimensional nature of brain activity. By combining whole-brain modeling, data augmentation, and deep learning, researchers mapped states of consciousness into a low-dimensional space where distances reflect similarities between states. They found an orderly trajectory from wakefulness to brain-injured patients, with coordinates related to functional modularity and structure-function coupling, both increasing as consciousness is lost. Model perturbations provided a geometric interpretation of state stability and reversibility. The work suggests conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.
Psychopharmacology
September 1, 2022
Camila Sanz, Federico Cavanna, Stephanie Müller et al.
Natural speech can reveal whether someone has taken a microdose of psilocybin. In a double-blind, placebo-controlled experiment, 34 healthy adults provided speech samples after consuming either 0.5 grams of psilocybin mushrooms or a placebo. Machine learning classifiers distinguished between the two conditions with high accuracy (AUC ~0.8), based on features such as verbosity and sentiment scores, though semantic variability did not differ significantly. This suggests that low doses of serotonergic psychedelics leave detectable signatures in unconstrained speech, offering a potential low-cost, non-invasive method for monitoring microdosing regimens.
arXiv Preprint Archive
July 11, 2022
Matthieu Gilson, Enzo Tagliazucchi, Rodrigo Cofré
Consciousness depends on complex, irreversible brain dynamics that produce entropy. By fitting a statistical model to fMRI data and calculating entropy production, researchers found a monotonic relationship: entropy production decreases as people move from wakefulness to deep sleep. This suggests that entropy production is a robust signature of consciousness, linking conscious states to the thermodynamic activity of the brain.
bioRxiv Preprint Server
September 2, 2021
Laura De la Fuente, Federico Zamberlán, Hernan Bocaccio et al.
preprint
The laws of physics are time-symmetric, but dissipative systems like the brain show a preferred temporal direction. Using a deep learning framework inspired by stochastic thermodynamics, researchers analyzed electrocorticography signals from non-human primates. Brain activity during conscious wakefulness could be distinguished from its time-reversed version with high accuracy, using both frequency and phase information. This ability was reduced during deep sleep and ketamine-induced anesthesia. Transitions between slow (≈20 Hz) and fast frequencies (> 40 Hz) mainly contributed to the temporal asymmetry seen during wakefulness. The findings suggest that a preferred temporal direction in neural activity correlates with conscious awareness, linking brain processes to the subjective experience of time's passage.
arXiv Preprint Archive
December 19, 2020
Yonatan Sanz Perl, Hernan Bocaccio, Ignacio Perez-Ipina et al.
Consciousness depends on brain activity that is far from thermodynamic equilibrium. Analyzing electrocorticography data from non-human primates during sleep and various anesthetics, and fMRI data from humans during deep sleep and propofol anesthesia, all states of reduced consciousness showed dynamics closer to equilibrium than conscious wakefulness. This was measured by entropy production and the curl of probability flux in phase space. Non-equilibrium macroscopic brain dynamics therefore serve as a robust signature of consciousness, offering a statistical mechanics approach to studying cognition and awareness.
arXiv Preprint Archive
August 6, 2020
Rodrigo Cofré, Rubén Herzog, Pedro A. M. Mediano et al.
Altered states of consciousness, such as those experienced during dreaming or meditation, offer a way to study how large-scale brain activity relates to different subjective experiences. This paper advocates a research program that combines bottom-up generative models of whole-brain activity, based on known properties of neural tissue, with top-down signatures proposed by theories of consciousness. The authors define altered states, discuss relevant brain-activity signatures, and introduce whole-brain models to explore the mechanisms behind these states. They argue that systematically investigating altered states through bottom-up modeling can clarify the biophysical, informational, and dynamical foundations of consciousness.