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.
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.
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 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.
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.
Frontiers in neuroscience
January 1, 2018
Camila Sanz, Federico Zamberlán, Earth Erowid et al.
3 citations
correction
No Summary
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.
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.
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.
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.