Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Translational Psychiatry
August 2, 2022
Federico Cavanna, Stephanie Müller, Laura Alethia de la Fuente et al.
130 citations
A double-blind placebo-controlled trial tested the effects of a low (0.5 g) dose of dried psilocybin mushrooms on 34 individuals beginning a microdosing protocol. The active dose produced more intense acute subjective effects than placebo, but only among participants who correctly guessed their condition. These effects coincided with reduced EEG theta-band power and preserved Lempel-Ziv broadband signal complexity. No evidence was found for enhanced well-being, creativity, or cognitive function; instead, small changes toward cognitive impairment appeared. The findings suggest that expectation, not the drug itself, accounts for many anecdotal benefits attributed to psilocybin microdosing.
Neuroscience
February 4, 2020
Rocío Martínez Vivot, Carla Pallavicini, Federico Zamberlán et al.
116 citations
Long-term meditation practice can increase the entropy of brain oscillations, indicating a more flexible and diverse neural state. Among three traditions—focused attention (Himalayan Yoga), open monitoring (Vipassana), and open awareness (Isha Shoonya Yoga)—Vipassana produced the largest entropy increases, especially in alpha and gamma bands. All traditions increased global coherence in the gamma band while reducing metastability, stabilizing gamma dynamics. Machine learning classifiers distinguished between traditions based on gamma entropy scalp distributions. These findings show that meditation can endogenously induce high-entropy brain states, similar to those seen with serotonergic psychedelics, but achieved through prolonged practice.
Consciousness and cognition
March 1, 2019
Charlotte Martial, Héléna Cassol, Vanessa Charland-Verville et al.
98 citations
Near-death experiences (NDEs) share consistent features across cultures, suggesting a common neurobiological basis. Analyzing semantic similarity between about 15,000 reports from 165 psychoactive substances and 625 NDE narratives, the NMDA receptor antagonist ketamine produced reports most similar to NDEs, followed by Salvia divinorum and serotonergic psychedelics like DMT. The similarity was driven by concepts of self and environmental consciousness, as well as therapeutic, ceremonial, and religious aspects of drug use. Ketamine may serve as a safe experimental model for NDE phenomenology, and endogenous NMDA antagonists might be released near death.
Frontiers in Integrative Neuroscience
November 1, 2018
Camila Sanz, Carla Pallavicini, Carla Pallavicini et al.
78 citations
Classic psychedelics produce a wide range of subjective effects influenced by the user's mindset and environment, and their common mechanism involves activation of the serotonin 5-HT2A receptor. The diversity of effects across different compounds may also stem from their binding affinities for multiple neurotransmitter receptors and transporters. By analyzing two binding affinity datasets alongside natural language processing of thousands of trip reports from Erowid's Experience Vaults, preliminary evidence showed that similarity in binding profiles across phenethylamines and tryptamines correlates with similarity in the language used to describe experiences.
Frontiers in Integrative Neuroscience
November 1, 2018
Camila Sanz, Carla Pallavicini, Carla Pallavicini et al.
78 citations
Classic psychedelics produce a wide range of subjective effects influenced by the user's mindset and environment, and their common mechanism involves activation of the serotonin 5-HT2A receptor. The diversity of effects across different compounds may also stem from their binding affinities for multiple neurotransmitter receptors and transporters. By analyzing two binding affinity datasets alongside natural language processing of thousands of trip reports from Erowid's Experience Vaults, preliminary evidence showed that similarity in binding profiles across phenethylamines and tryptamines correlates with similarity in the language used to describe experiences.
Journal of Psychedelic Studies
May 6, 2021
Federico Cavanna, Carla Pallavicini, Virginia Milano et al.
31 citations
During the COVID-19 pandemic, people who had used psychedelic drugs at least once in their lives reported higher positive affect and personality traits linked to resilience, such as greater openness and lower conscientiousness, compared to those who had not. Among 5,618 participants (average age 29, 72% female), 32% reported lifetime psychedelic use. The number of past psychedelic experiences predicted higher scores on a measure of plasticity. No evidence linked lifetime psychedelic use to impaired mental health indicators. Other psychoactive drugs showed opposite associations with mental health.
Frontiers in Psychiatry
November 5, 2021
Enzo Tagliazucchi, Federico Zamberlán, Federico Cavanna et al.
23 citations
Inhaled DMT, a classic psychedelic, produces short but profound shifts in consciousness. In 35 healthy volunteers, electroencephalography recorded before and during the drug's acute effects in a natural setting showed marked reductions in alpha and beta brain oscillations and increases in delta, theta, and gamma power, particularly in posterior regions. The power of fronto-temporal theta oscillations inversely correlated with feelings of unity and transcendence—core features of mystical-type experiences. These findings suggest that baseline brain activity prior to psychedelic use may help predict the likelihood of such experiences, which are linked to lasting well-being and improved therapeutic outcomes.
bioRxiv (Cold Spring Harbor Laboratory)
August 20, 2020
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
17 citations
preprint
Inhaled DMT, a short-acting psychedelic found in plants and animals, was studied in 35 experienced participants in natural settings using wireless EEG and questionnaires. DMT reduced alpha brain waves (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) waves. Increases in gamma power correlated with reports of mystical-type experiences. DMT also altered global synchrony and metastability in gamma and alpha bands and increased signal complexity. These findings align with prior psychedelic research and suggest EEG markers for mystical experiences in natural contexts, underscoring the value of studying these compounds in real-world settings.
bioRxiv (Cold Spring Harbor Laboratory)
December 7, 2021
Federico Cavanna, Stephanie Müller, Laura Alethia de la Fuente et al.
8 citations
preprint
A double-blind placebo-controlled trial tested the effects of a low (0.5 g) sub-hallucinogenic dose of dried psilocybin mushrooms in 34 individuals planning to microdose. Acute subjective effects were significantly stronger with the active dose than with placebo, possibly due to unblinding. For other measures—including creativity, perception, cognition, and brain activity—the results were null or showed a trend toward cognitive impairment and, in electroencephalography, reduced theta band spectral power. These findings suggest that expectation effects may account for some of the anecdotal benefits people report from microdosing psilocybin.
Communications biology
March 11, 2025
Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al.
6 citations
The transition into a psychedelic brain state is often overlooked in favor of static descriptions of acute effects. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the work shows that a transient of heightened reactivity in fronto-parietal regions and visual cortices correlates with serotonin 5HT2a receptor density. Simulated perturbations suggest that minimal disturbances can achieve maximal effects during this brief period, and the temporal evolution of these features aligns with pharmacokinetics. These findings indicate a mechanism for how short psychedelic episodes may exert a lasting influence over time.
Journal of Cognitive Neuroscience
December 30, 2025
Evan Lewis-Healey, Carla Pallavicini, Federico Cavanna et al.
4 citations
The psychedelic drug DMT rapidly reorganizes conscious experience and brain activity, but the link between brain dynamics and subjective effects remains unclear. In a blinded, dose-dependent study, 19 participants received 20 mg or 40 mg of DMT. The higher dose produced more intense visual hallucinations and emotional experiences. Electroencephalography data showed that alpha power and permutation entropy best tracked moment-to-moment changes in subjective experience, while Lempel-Ziv complexity—previously thought to be a strong correlate—showed the weakest association. The findings indicate that the relationship between neural complexity and psychedelic phenomenology is less straightforward than hypothesized.
bioRxiv (Cold Spring Harbor Laboratory)
November 1, 2023
Stephanie Müller, Federico Cavanna, L. de la Fuente et al.
3 citations
preprint
High doses of psilocybin mushrooms cause people to explore paintings with more local, less random eye movements, making their gaze patterns less entropic. Participants also reported stronger emotional responses and a greater state of flow under the high dose. These effects are consistent with psilocybin altering the perception of low-level visual features like textures, shapes, and colors. The findings demonstrate that eye-tracking under naturalistic conditions can objectively measure psychedelic-induced perceptual changes, supporting greater ecological validity.
bioRxiv Preprint Server
March 11, 2021
Enzo Tagliazucchi, Federico Zamberlan, Federico Cavanna et al.
3 citations
preprint
Inhaled DMT, a classic psychedelic, produces brief but profound changes in consciousness that vary with context. Using wireless EEG and source imaging, researchers mapped changes in neural oscillations. Frontal and temporal theta power inversely correlated with feelings of unity and transcendence—hallmarks of mystical-type experiences. A machine learning model confirmed the robustness of these results. The findings align with the idea that pre-drug mindset influences subjective experience. Priming individuals to lower theta power before taking a serotonergic psychedelic might increase the likelihood of mystical-type experiences, potentially enhancing well-being and therapeutic outcomes.
Neuroscience of Consciousness
January 1, 2025
Stephanie Muller, 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 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.
bioRxiv Preprint Server
April 22, 2026
Nicolás Bruno, Federico Cavanna, Federico Zamberlan 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.
Zenodo (CERN European Organization for Nuclear Research)
January 7, 2026
Carla Pallavicini
Psilocybin combined with compassion-focused imagery alters resting-state brain network connectivity and self-reported psychological measures for up to six months. Functional MRI data collected before and after the psilocybin experience show changes in resting-state network connectivity matrices. Longitudinal psychometric assessments indicate lasting effects. The dataset supports transparency and reproducibility of the original findings.
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.
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.
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.
bioRxiv Preprint Server
July 2, 2020
Yonatan Sanz Perl, Carla Pallavicini, Ignacio Pérez Ipiña et al.
preprint
The level of consciousness—how conscious someone is—is often measured by how similar their brain activity is to normal wakefulness. However, this approach misses important information about how stable that state is. Using computer models of the whole brain, the authors show that the stability of a conscious state—how easily it can be disrupted—provides additional, complementary information. They propose a new framework that sorts brain states by both their similarity to wakefulness and their stability, which helps distinguish between different types of unconsciousness: natural sleep, anesthesia, and brain injury. This framework offers a more complete way to characterize and differentiate states of consciousness.