Frontiers in Human Neuroscience
January 1, 2014
Robin Carhart‐Harris, Robert Leech, Peter J. Hellyer et al.
1,289 citations
Entropy, a measure of uncertainty or disorder, is applied to brain function and consciousness, focusing on the psychedelic state induced by psilocybin. The psychedelic state is considered a primary or primitive state of consciousness, characterized by elevated entropy in brain function, including a greater repertoire of functional connectivity motifs that form and fragment over time. This suggests primary states may exhibit criticality, a transition zone between order and disorder. Normal waking consciousness suppresses entropy, operating just below criticality, which constrains cognition and enables metacognitive functions like reality-testing and self-awareness. Entry into primary states involves collapse of default-mode network activity and decoupling from medial temporal lobes. These hypotheses can be tested by comparing brain activity in REM sleep, early psychosis, normal waking consciousness, and anesthesia.
Human Brain Mapping
July 3, 2014
Enzo Tagliazucchi, Robin Carhart‐Harris, Robert Leech et al.
423 citations
Psilocybin, the active compound in magic mushrooms, increases the variability and range of brain activity and connectivity. Using fMRI, fifteen healthy volunteers were scanned before, during, and after receiving psilocybin or a placebo. Psilocybin raised the variability of blood-oxygen-level-dependent signals in the hippocampi and anterior cingulate cortex. Changes in the spectral behavior of brain signals were limited to higher-order networks, including the default mode, executive control, and dorsal attention networks. The brain also explored a wider repertoire of connectivity states after psilocybin than under control conditions. These findings help explain the unconstrained, hyper-associative quality of consciousness in the psychedelic state.
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.
Frontiers in Neuroscience
January 22, 2018
Camila Sanz, Federico Zamberlán, Earth Erowid et al.
112 citations
Subjective reports of experiences under hallucinogens like LSD are semantically most similar to reports of high-lucidity dreams, while Datura (a deliriant) resembles low-lucidity dreams. Sedatives, stimulants, antipsychotics, and antidepressants rank lowest in similarity to dream reports. Frequent words across both dreams and hallucinogen experiences include perception-related terms ("see," "visual," "color"), emotion ("fear"), setting ("inside," "outside"), and family members ("mom," "dad"). The analysis confirms that hallucinogens produce experiences with the highest semantic similarity to dreams among all psychoactive substances.
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.
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.
Scientific Reports
October 20, 2020
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
60 citations
Psychedelic drugs such as lysergic acid diethylamide, which activate the serotonin 2A receptor, produce profound changes in consciousness and increase entropy in spontaneous neural activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonergic neuromodulation. The model reproduced the overall entropy rise seen in previous experiments. Entropy changes were not uniform: some brain regions showed increased entropy while others showed decreases, indicating a topographical reconfiguration driven by receptor activation. At the whole-brain level, this reconfiguration was not well explained by receptor density but was closely related to the brain's anatomical connectivity topology.
Scientific reports
April 17, 2023
Rubén Herzog, Pedro A M Mediano, Fernando E Rosas et al.
51 citations
Psychedelic drugs such as LSD, which activate the serotonin 2A receptor, produce profound changes in consciousness and are linked to increased entropy in spontaneous brain activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonin neuromodulation. The model reproduced the overall rise in neural entropy seen in prior experiments. Entropy increased across all brain regions, with the largest effects in visuo-occipital areas. At the whole-brain level, this reconfiguration was not well explained by the density of serotonin 2A receptors but was closely related to the topological properties of the brain's anatomical connectivity.
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.
Network Neuroscience
January 1, 2022
Josephine Cruzat, Yonatan Sanz Perl, Anira Escrichs et al.
28 citations
Psychedelic drugs like LSD and psilocybin may treat neuropsychiatric disorders by dose-dependently altering the brain's functional hierarchy—the organization of neural activity across regions. Using a turbulence framework that measures local synchronization (vorticity) in both space and time, researchers found that both drugs produce consistent and distinct effects, particularly compressing the default mode network, a higher-level network. These findings support the hypothesis that psychedelics modulate the functional hierarchy and provide a quantitative comparison of how LSD and psilocybin change brain dynamics, with implications for therapeutic use.
Cerebral cortex (New York, N.Y. : 1991)
August 1, 2024
Evan Lewis-Healey, Enzo Tagliazucchi, Andres Canales-Johnson et al.
27 citations
Intentional breathing techniques (breathwork) can induce altered states of consciousness similar to those produced by psychedelics. By tracking subjective experiences moment-by-moment alongside portable EEG recordings across 301 sessions from 14 novice participants, researchers found that psychedelic-like experiences—especially intense bliss—corresponded with increased neural complexity (Lempel-Ziv complexity) and changes in the aperiodic exponent of brain activity, but not with alpha brainwave power. These non-linear neural features map onto both broad positive experiences and specific psychedelic-like states, suggesting breathwork alters consciousness through mechanisms distinct from simple relaxation or meditation.
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.
Frontiers in Pharmacology
March 22, 2022
Enzo Tagliazucchi
20 citations
Psychedelics profoundly alter subjective experience, sometimes with lasting effects, yet how they affect language production is understudied. This review examines two aspects: how acute psychedelic effects impact speech organization regardless of semantic content, and how analyzing semantic content of written retrospective reports can characterize subjective effects. Computational analysis of language production can partially predict therapeutic outcomes, relate psychedelic effects to other altered states and psychiatric disorder symptoms, and investigate neurochemical profiles and mechanisms of action. The authors conclude that analyzing brief interviews before, during, and after acute effects can expand scientific conclusions, and they list open questions for future research.
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.
Psychology of Consciousness Theory Research and Practice
June 12, 2025
Etzel Cardeña, Aviva Berkovich‐ohana, Katja Valli et al.
11 citations
A multidisciplinary, international group used taxonomic principles and a modified Delphi method to create a taxonomy of altered states of consciousness based on central phenomenological features. They identified eight distinct states, some with subcategories: proto and transitional, delirium, minimal to no awareness, experiential detachment, enhanced physicality, altered identity, imaginary/fantasy/visionary, and unity/mystical. The authors hope this taxonomy will foster conceptual clarity and stimulate research across specializations, helping reveal what is common and different across triggers and antecedents of altered states, and encouraging phenomenological, psychological, cultural, and neuroscientific understanding.
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.
Frontiers in neuroscience
January 1, 2018
Camila Sanz, Federico Zamberlan, Earth Erowid et al.
3 citations
correction
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