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.
Physical review. E
July 28, 2021
Yonatan Sanz Perl, Hernan Bocaccio, Carla Pallavicini et al.
82 citations
Conscious wakefulness is characterized by brain dynamics far from thermodynamic equilibrium, while states of reduced consciousness—such as deep sleep and anesthesia induced by propofol, ketamine, or ketamine plus medetomidine—operate closer to equilibrium. This conclusion comes from analyzing electrocorticography data from nonhuman primates and functional magnetic resonance imaging data from humans. Entropy production and the curl of probability flux in phase space reliably distinguished conscious from unconscious states. The findings establish nonequilibrium macroscopic brain dynamics as a robust signature of consciousness and offer a statistical mechanics framework for studying cognition and awareness.
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.
J Psychopharmacol
February 10, 2021
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
73 citations
Inhaled N,N-dimethyltryptamine (DMT) in natural settings reduces alpha brainwave power (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) power. Gamma power increases correlate with reports of mystical-type experiences. DMT also raises global synchrony and metastability in the gamma band and lowers them in the alpha band. These findings align with prior lab-based psychedelic research and suggest EEG markers for mystical experiences in real-world contexts, underscoring the value of studying psychedelics in natural settings.
Communications Biology
June 29, 2022
Anira Escrichs, Yonatan Sanz Perl, Carme Uribe et al.
67 citations
Different brain states—resting, meditating, deep sleep, and disorders of consciousness after coma—are underpinned by distinct spatiotemporal dynamics that can be characterized using turbulence theory. Non-conscious states tend to be more synchronous, while conscious states are more asynchronous, but the work goes beyond this simple dichotomy. A model-free analysis of human neuroimaging data applied Kuramoto's turbulence framework with coupled oscillators and measured information cascades across spatial scales. A complementary model-based approach used exhaustive computer simulations of whole-brain models fitted to those measures to study information encoding. The framework shows that turbulence theory provides excellent tools for describing and differentiating between brain states.
Neuroimage
June 24, 2019
Carla Pallavicini, Martina G. Vilas, Mirta Villarreal et al.
66 citations
Classic serotonergic psychedelics and dissociative drugs like ketamine produce overlapping subjective effects despite different pharmacological mechanisms. Using source-localized magnetoencephalography, researchers found that LSD, psilocybin, and ketamine all caused widespread broadband reductions in spectral power. Machine learning classifiers trained on one pair of drugs could identify the third, confirming similarity. Functional connectivity analysis revealed decreases in low alpha and theta bands specific to LSD and psilocybin, linked to 5-HT2A agonism, while low beta band decreases were common to all three drugs. These findings quantify shared large-scale brain activity patterns across drug classes and suggest that beta band decoupling is an effect shared between NMDA antagonists and 5-HT2A agonists.
Conscious Cogn
December 8, 2020
Camila Sanz, Carla Pallavicini, Facundo Carrillo et al.
34 citations
Language produced under the influence of LSD shows increased entropy and reduced semantic coherence, consistent with a state of heightened neural entropy. Non-semantic analysis of speech organization revealed increased verbosity and a reduced lexicon, changes more similar to manic psychoses than to schizophrenia, as confirmed by direct comparison with reference samples. Features related to language organization allowed machine learning classifiers to identify speech under LSD with accuracy comparable to that obtained by examining semantic content. These results provide a quantitative characterization of disorganized natural speech as a landmark feature of the psychedelic state.
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.
Journal of Cannabis Research
July 17, 2020
Laura Alethia de la Fuente, Federico Zamberlán, Andrés Sánchez Ferrán et al.
30 citations
Machine learning classifiers distinguished between Cannabis sativa and Cannabis indica cultivars based on user-reported flavours and subjective effects with high accuracy. Analysis of a large dataset from Leafly.com and chemical composition data from Psilabs.org revealed significant correlations between terpene and cannabinoid content and subjective effect and flavour tags. Reported effects clustered into three groups: unpleasant, stimulant, and soothing. Terpene profiles matched user perceptual characterizations, particularly for terpene-flavours associations. The findings suggest that flavour perception could serve as a reliable marker to indirectly characterize cannabis psychoactive effects, as terpene content is robustly inherited and less influenced by environmental factors.
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 Zamberlán, 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.
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.
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 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 (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.