bioRxiv (Cold Spring Harbor Laboratory)
January 3, 2023
Saampras Ganesan, Bradford A. Moffat, Nicholas T. van Dam et al.
1 citation
preprint
Using ultra-high strength 7 Tesla fMRI, a pilot study scanned 10 beginner meditators during focused attention meditation and rest. Meditation significantly reduced activity in Default-mode network hubs—antero-medial prefrontal cortex, posterior cingulate cortex, precuneus—and in visual and thalamic regions, even after adjusting for physiological differences between conditions. State Mindfulness Scale scores significantly increased after the meditation session and remained elevated at a two-week follow-up. The findings support that focused attention meditation attenuates default-mode activity linked to self-referential processing, establishing the feasibility of 7 Tesla fMRI for meditation research.
bioRxiv (Cold Spring Harbor Laboratory)
July 14, 2022
Sandeep Singh, Alexander Botvinnik, Orr Shahar et al.
1 citation
preprint
In mice, psilocybin reduced marble-burying, a behavior linked to obsessive-compulsive disorder, as effectively as the antidepressant escitalopram. This effect was not blocked by a 5-HT2A antagonist or a 5-HT1A antagonist, indicating neither receptor is essential for psilocybin's anti-obsessional action. The 5-HT1A partial agonist buspirone also reduced marble-burying, but combining buspirone with psilocybin did not enhance the effect. Staggered doses of psilocybin over 3.5 hours had no effect, and the effect of a single injection was not persistent. Importantly, buspirone blocked psilocybin's head-twitch response, a rodent correlate of psychedelic effects, suggesting buspirone could prevent psychedelic effects without interfering with anti-obsessional benefits.
bioRxiv (Cold Spring Harbor Laboratory)
July 3, 2022
Mohamed Sherif, Mostafa Z. Khalil, Rammohan Shukla et al.
1 citation
preprint
Synaptic atrophy in major depressive disorder may impair the brain's ability to confidently predict future affective states, even when predictions remain accurate. Using a temporal memory algorithm that mimics a single neocortical layer with Hebbian learning, researchers simulated depression by progressively destroying synapses. Destroying 50% of synapses slightly reduced the number of predictions, but a 25% reduction distinctly lowered prediction confidence. This suggests that in depression, interoceptive cortices become stuck in limited affective states with high prediction error. Treatments like ketamine and psilocybin may help by growing new synapses, enabling more confident and futuristic predictions.
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)
June 17, 2021
Karina Karmirian, Livia Goto‐silva, Juliana Nascimento et al.
1 citation
preprint
Harmine, a β-carboline found in the ayahuasca vine Banisteriopsis caapi, upregulates proteins in human brain organoids that are involved in synaptic vesicle cycling, cytoskeleton-dependent transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling. Treatment with harmine also increased levels of Akt and phosphorylated CREB after 24 hours. These findings point to cellular and molecular pathways that may explain harmine's potential neuroprotective effects, which have been suggested by previous animal studies to include anti-inflammatory and antioxidant activities. The work advances understanding of how harmine might contribute to the antidepressant effects observed with ayahuasca.
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 (Cold Spring Harbor Laboratory)
March 9, 2019
Andria Pelentritou, Levin Kuhlmann, John Cormack et al.
1 citation
preprint
Equivalent stepwise subanesthetic doses of the NMDA-antagonists nitrous oxide (N2O) and xenon (Xe) produce distinct, frequency-dependent changes in cortical oscillatory source power, measured with simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). At the highest Xe concentration (42%, 1.30 MAC-awake), delta and theta band power significantly increased in both MEG and EEG. N2O administration reduced frontal alpha power more strongly than equivalent Xe doses. N2O alone increased MEG (but not EEG) high-frequency gamma power, with occipital low gamma and widespread high gamma rises. These results demonstrate divergent MEG and EEG signatures of dissociative anesthesia.
bioRxiv (Cold Spring Harbor Laboratory)
July 24, 2018
Greg R. Boyce, Emile Gluck-Thaler, Jason C. Slot et al.
1 citation
preprint
Some entomopathogenic fungi keep their insect hosts alive while releasing spores, a behavior that improves spore dispersal. Metabolomics of four populations of periodical cicadas infected with Massospora cicadina revealed the plant-associated amphetamine cathinone, while annual cicadas infected with Massospora platypediae or Massospora levispora contained the mushroom-associated tryptamine psilocybin; the latter two fungi appear to be a single species. The absence of certain fungal enzymes needed to produce cathinone and psilocybin, along with undetectable intermediate metabolites or gene orthologs, suggests novel biosynthesis pathways in Massospora. The neurogenic activity of these compounds indicates that the extended phenotype of Massospora, which alters cicada behavior to maximize spore dissemination, is chemically induced.
bioRxiv (Cold Spring Harbor Laboratory)
October 16, 2017
Suresh Muthukumaraswamy, David T. J. Liley
1 citation
preprint
The arhythmical, scale-free brain activity (1/f β) that dominates neurophysiological recordings is dynamically linked to oscillatory alpha rhythms and is systematically modulated by excitation-inhibition balance. Using IRASA to separate arhythmical from oscillatory activity, the authors show that alpha power correlates over time with the high-frequency power-law exponent βhf, and participants with higher alpha power also have higher βhf. Pharmacological manipulations with tiagabine, perampanel, ketamine, and LSD in MEG, and propofol and ketamine in monkey ECoG, reveal consistent effects of excitation-inhibition balance on both high- and low-frequency β exponents.
bioRxiv (Cold Spring Harbor Laboratory)
Kathleen A. Trychta, Brandon K. Harvey
1 citation
preprint
Hyperthermia—elevated body temperature—triggers the abnormal secretion of proteins normally retained inside the endoplasmic reticulum (ER), a process called ER exodosis. The club drugs MDMA (ecstasy) and caffeine, alone or combined, worsen this protein leakage in a cellular model. Hyperthermia also activates the unfolded protein response (UPR), a cellular stress pathway, but the drugs do not alter most UPR-related gene expression despite increasing ER exodosis of UPR proteins. One exception: MDMA raised BiP/Grp78 mRNA levels under hyperthermia. These results suggest that using club drugs in hot environments disrupts ER protein balance, potentially increasing cell toxicity.
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
bioRxiv (Cold Spring Harbor Laboratory)
Iga Adamska, Karolina Finc
1 citation
preprint
Listening to music while under the influence of LSD alters the brain's moment-to-moment patterns of activity, particularly in networks linked to attention and task performance. In a study of 15 participants who underwent functional MRI scans after taking LSD or a placebo, the combination of music and LSD changed how long the brain stayed in a task-positive state. LSD alone, regardless of music, affected the dynamics of a state involving the default mode, somatomotor, and visual networks. Music itself appeared to have a lingering effect on resting-state brain activity, especially on networks associated with tasks. These findings suggest that music, as part of the setting, can shape the psychedelic experience at a neural level.
bioRxiv (Cold Spring Harbor Laboratory)
Shawn. M. Aarde, Pai-Kai Huang, Michael A. Taffe
1 citation
preprint
In rats, high ambient temperature (30°C) increases the acquisition of intravenous self-administration of MDMA more than low temperature (20°C). Initially, MDMA caused similar hypothermia in both temperature groups, but this effect diminished over training in the hot group. Activity levels, initially lower in the hot group, became similar by the end of training. When temperature conditions were swapped, rats trained in the hot condition increased MDMA intake under cold, while those trained in the cold modestly decreased intake under hot. Rats with higher MDMA intake showed blunted hypothermia after non-contingent MDMA. High temperature alone raised brain reward thresholds, and MDMA lowered thresholds below baseline only at low temperature. The findings suggest that high temperature enhances MDMA self-administration acquisition through an aversive effect rather than thermoregulatory motivation.
bioRxiv (Cold Spring Harbor Laboratory)
Matthew J. Baggott, Kathleen J. Garrison
1 citation
preprint
MDMA (ecstasy) use can cause dangerously low blood sodium levels (hyponatremia), especially when people drink too much water. In two double-blind, placebo-controlled studies, healthy volunteers who took MDMA did not show increased levels of the hormone that normally regulates water balance (ADH or copeptin), but their blood sodium dropped more than with placebo when they drank standardized amounts of water. Women tended to have lower baseline sodium, but this did not significantly interact with MDMA. The findings indicate that consuming hypotonic fluids during MDMA use poses a significant risk of hyponatremia, which should be anticipated and managed in clinical and recreational settings.
bioRxiv (Cold Spring Harbor Laboratory)
Lucas Dwiel, Angela Henricks, Elise Bragg et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) acutely reduces low-frequency electrical activity across the brain in rats, an effect that returns to normal after 24 hours. However, brain stimulation applied during a window of heightened neuroplasticity 24 hours after LSD produces larger and distinct changes in brain activity compared to stimulation after a placebo. This proof-of-concept finding suggests that psychedelic drugs may work in combination with brain stimulation to achieve enhanced effects on brain activity, with future work needed to assess impacts on behavior.
bioRxiv (Cold Spring Harbor Laboratory)
July 17, 2026
Yoko Nagai
Mental imagery vividness is linked to cardiovascular physiology. Elevated diastolic blood pressure during an autonomic challenge predicted reduced vividness of mental images, especially for disgust and neutral scenes. Acute autonomic changes from a tilt table did not alter imagery vividness overall. The findings support the idea that mental imagery emerges from interactions between neural and bodily systems, and suggest cardiovascular function as a potential contributor to altered imagery experiences.
bioRxiv (Cold Spring Harbor Laboratory)
July 16, 2026
Filip Novický, Nikola Jajcay, Jaroslav Hlinka
Neural avalanches—bursts of coordinated brain activity—are typically studied using scale-free statistics, but their detailed spatiotemporal structure and recurrence have been difficult to analyze due to variability in duration and spatial extent. A new method using flexible alignment with unbalanced optimal transport and subsequence dynamic time warping allows comparison of events of different lengths and configurations. Applied to 64-channel EEG data from 63 participants in the PsiConnect psilocybin study, hierarchical clustering revealed 12 recurring propagation patterns. Under psilocybin, oscillating sequences—those with alternating polarity and spatial propagation—were reduced relative to stable sequences, shifting the balance toward stable patterns. This effect was confirmed by a permutation test and largely driven by one cluster, indicating specific neural dynamics temporally affected by psilocybin.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2026
Natasha L. Mason, Eline Chm Haijen-Bongers, Kim P. C. Kuypers et al.
Female participants reported more intense subjective effects from psilocybin, 2C-B, and LSD than male participants, including feeling more strongly under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects consistent across the three drugs. No sex differences were found in empathy measures or peak drug concentrations in blood. These findings suggest pharmacodynamic mechanisms—how the body responds to the drug—rather than pharmacokinetic differences in drug exposure explain the sex differences. The results have implications for dosing, informed consent, and safety monitoring in psychedelic research.
bioRxiv (Cold Spring Harbor Laboratory)
July 3, 2026
Sébastien Czajko, Jelle Zorn, Oussama Abdoun et al.
Nondual meditation, specifically Open Presence (OP) practice, is associated with reduced bodily self susceptibility and increased large-scale integration of functional brain networks. Expert meditators with over 10,000 hours of practice showed lower global network eccentricity during OP compared to novices, particularly in dorsal attention, ventral attention, and frontoparietal networks, indicating greater integration. These neural patterns correlated positively with measures of bodily self illusion and negatively with cognitive defusion, a construct reflecting reduced self-grasping toward thoughts. The findings suggest that nondual awareness involves alterations in self-representation and large-scale functional brain integration.
bioRxiv (Cold Spring Harbor Laboratory)
July 2, 2026
Marco S. Fabus, Stephen Zerfas, Alex Gruver et al.
Jhana meditation produces states of self-reinforcing bliss that may be useful in clinical and scientific settings, but research has been limited by scarce data and few expert practitioners. To address this, the authors release the largest open-access dataset of electroencephalographic and physiological recordings from expert Jhana meditators, comprising over 100 hours of data from 26 subjects across three retreats. The dataset includes example analysis code. This resource aims to enable broader collaboration and advance understanding of internally generated altered states of consciousness.
bioRxiv (Cold Spring Harbor Laboratory)
July 1, 2026
Fernando Lehue, Iván Mindlin, Carlos Coronel-Oliveros et al.
Disorders of consciousness are linked to large-scale changes in brain dynamics, but the structural factors behind these changes are unclear. Using a whole-brain computational model constrained by diffusion MRI-derived connectivity, the authors show that a node's integration within the structural connectome, measured by a spectral integration metric, strongly predicts its impact on global brain dynamics. Lesions to highly integrative hubs, especially in posterior medial regions like the precuneus and posterior cingulate cortex, drive the system toward low-complexity dynamical regimes resembling disorders of consciousness. Increasing excitability in these regions restores healthy-like dynamics in silico. Perturbations to weakly integrated regions have limited global effects, explaining why damage to specific hubs disproportionately disrupts conscious brain activity.
bioRxiv (Cold Spring Harbor Laboratory)
June 30, 2026
Blake A Fordyce, Yi-Ting Chiu, Nicholas A. Wright et al.
Activation of mGluR2, the primary presynaptic autoreceptor for glutamate in the brain, attenuates the behavioral and electrophysiological effects of psychedelics. The mechanisms behind this are debated, with two competing hypotheses: direct actions via mGluR2/5-HT2A heterodimers, or presynaptic inhibition of glutamate release. In mice expressing tagged receptors, mGluR2 agonist pretreatment reduced the head twitch response induced by the psychedelic DOI. Multiple orthogonal in vivo and in vitro approaches found no evidence for receptor colocalization or oligomerization under basal or agonist-exposed conditions, nor for mGluR2-mediated modulation of 5-HT2A ligand binding. The findings support models where mGluR2 signaling modulates 5-HT2A receptor activity in layer V pyramidal neurons rather than requiring mGluR2/5-HT2A multimers.
bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Robin Carhart‐Harris et al.
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual.
bioRxiv (Cold Spring Harbor Laboratory)
June 23, 2026
Deysha Poyser, Eugenio Rodríguez
Intense aesthetic experiences involve distinct neural states rather than simply stronger versions of ordinary responses. Electroencephalography recordings from 22 Chilean participants viewing 113 artworks revealed threshold-specific neurodynamics: beta-band power and its interaction with the aperiodic 1/f exponent predicted the transition to the most intense response during viewing, while the aperiodic exponent alone predicted the shift from very low to higher intensity after viewing. Individual differences in alpha and gamma activity improved predictive performance, indicating meaningful neural variability in aesthetic processing. These findings support the hypothesis that being intensely moved constitutes a qualitatively distinct neural state.
bioRxiv (Cold Spring Harbor Laboratory)
June 22, 2026
Julie Boyer, Nathan Beraud, Benoît Béranger et al.
Conscious perception is linked to all-or-none late brain activations that exhibit bifurcation dynamics, even without a task. Using fMRI and near-threshold auditory stimulation, this study identified the brain networks producing these bifurcations and how they differ depending on task context. Stimulus intensity modulated activity across broad networks including sensory and extra-sensory regions like the prefrontal cortex in both task and no-task contexts. These networks had both shared and distinct components. Single-trial modeling revealed bifurcation dynamics beyond primary sensory cortices and allowed prediction of conscious perception on individual trials in both contexts, resolving previous conflicting results and showing common networks and dynamics underlying conscious perception regardless of task.