bioRxiv (Cold Spring Harbor Laboratory)
October 9, 2023
Marina D. Luccioni, Jules T. Wyman, Edgard O. Espinoza et al.
2 citations
preprint
The Sonoran Desert Toad is the only animal known to secrete the psychedelic compound 5-MeO-DMT as a chemical defense, but whether it produces this compound itself or acquires it from its diet was unclear. Analyzing toxin gland secretions and stomach contents from wild toads and other amphibians in and around Tucson, Arizona, showed that all Sonoran Desert Toads had high concentrations of 5-MeO-DMT, while other toad species did not. The diet of the Sonoran Desert Toad was similar to that of other amphibians, suggesting no special dietary source. Slight differences in diet between toads from native and urban habitats were observed. These findings indicate that diet is not directly linked to 5-MeO-DMT production, supporting the idea that the toads either synthesize the compound themselves or rely on a microbial partner.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2023
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
2 citations
preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.
bioRxiv (Cold Spring Harbor Laboratory)
May 18, 2023
David Aquilué-Llorens, Jennifer S. Goldman, Alain Destexhe
2 citations
preprint
Whole-brain models that simulate neural activity across scales show that spike-frequency adaptation robustly drives synchronized slow-wave activity, a hallmark of unconscious brain states such as sleep and anesthesia. By exploring the parameter space of the TVB-AdEx model using high-performance computing, the authors find that slow-wave occurrence often coincides with a closer alignment between functional and structural brain connectivity. Hyperpolarization can also generate unconscious-like synchronized Up and Down states, potentially explaining how anesthetics work. The model's parameter space reproduces experimentally observed features of sleep and anesthesia.
bioRxiv (Cold Spring Harbor Laboratory)
February 16, 2023
Pablo Mallaroni, Natasha L. Mason, Johannes T. Reckweg et al.
2 citations
preprint
2C-B, a hallucinogenic phenethylamine derived from mescaline, produces subjective psychedelic effects that are shorter in duration and milder than those of psilocybin. In a double-blind, placebo-controlled study with 22 healthy participants experienced with psychedelics, 2C-B (20 mg) induced alterations of waking consciousness of a psychedelic nature, but dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution were largest under psilocybin (15 mg). Both compounds caused equivalent psychomotor slowing and spatial memory impairments compared to placebo, and neither produced empathogenic effects on the Multifaceted Empathy Test. 2C-B also induced transient pressor effects similar to psilocybin, with self-reported effects largely resolving within 6 hours. These findings support categorizing 2C-B as a subjectively 'lighter' psychedelic.
bioRxiv (Cold Spring Harbor Laboratory)
April 29, 2022
Devin P. Effinger, Sema G. Quadir, M. C. Ramage et al.
2 citations
preprint
A single dose of psilocin, the active metabolite of psilocybin, produces sex-specific, time-dependent, and lasting changes in central amygdala (CeA) activity and reactivity to an aversive air-puff stimulus in mice. Psilocin acutely increased CeA activity in both sexes and increased stimulus-specific CeA reactivity in females but not males. In males, psilocin caused time-dependent decreases in reactivity from 2 to 28 days after administration, while females showed no such decrease. Behavioral threat responses also changed in a sex-dependent manner, with no effects on exploratory behavior or locomotion. These findings suggest enduring, sex-specific alterations in CeA function underlie psilocin's therapeutic effects in affective disorders.
bioRxiv (Cold Spring Harbor Laboratory)
March 2, 2022
Andrew Gaddis, Daniel E. Lidstone, Mary Beth Nebel et al.
2 citations
preprint
Psilocybin, a classic psychedelic, alters perception and cognition by affecting connectivity between the thalamus and cortex. Using a novel analysis of resting-state fMRI data, this study found that psilocybin changes the functional organization within specific thalamic nuclei—primarily the mediodorsal and pulvinar nuclei—and alters their connections with visual and default mode networks. These changes correlated with subjective drug effects. When the thalamus was treated as a single unit, a numerical but not statistically significant increase in thalamocortical connectivity was observed, suggesting that psilocybin causes widespread modest increases offset by strong focal decreases in relevant nuclei.
bioRxiv (Cold Spring Harbor Laboratory)
June 23, 2021
Aurora Savino, Charles D. Nichols
2 citations
preprint
Psychedelic drugs are being studied as potential treatments for psychiatric conditions like mood and substance use disorders. The 5-HT2A receptor is their main molecular target, and early research indicated effects on neuroplasticity gene expression. By analyzing RNA-seq data from the prefrontal cortex of rats chronically treated with lysergic acid diethylamide (LSD), researchers found that psychedelics rewire gene co-expression networks, making them less centralized but more complex, with an overall increase in signaling entropy—a feature of highly plastic systems. This molecular signaling entropy mirrors increased brain entropy observed in human neuroimaging studies, suggesting a shared underlying mechanism. Network topology analysis also identified potential transcriptional regulators and implicated different cell types in psychedelic activity.
bioRxiv (Cold Spring Harbor Laboratory)
February 2, 2021
E. Amit Romach, M. Nachliely, Olivia Moran et al.
2 citations
preprint
Psychedelics such as LSD and psilocybin, increasingly used by cancer patients to relieve anxiety and depression, may interfere with immune-based cancer treatments like immune checkpoint inhibitors. Preclinical data suggest that consuming psychedelics during such therapy could negatively impact tumor growth and diminish the therapeutic benefits of immune checkpoint inhibitors. The authors call for further research to validate these findings, given the rising use of cannabinoids and psychedelics among cancer patients receiving immune-based treatments.
bioRxiv (Cold Spring Harbor Laboratory)
July 30, 2020
Sergio Hernández, Roberto Dorta‐Guerra, José Suero et al.
2 citations
preprint
Long-term practitioners of Sahaja Yoga Meditation had larger grey matter volume overall compared to non-meditators, with significant differences in four of sixteen lobe areas: the right temporal and frontal lobes, the left frontal lobe, and the brainstem. When examining 116 finer brain subdivisions, eleven areas showed significant differences, with the right hemisphere more affected. These neuroplastic changes may reflect emotional and attentional control developed through the practice. The ad-hoc statistical method used revealed more significant brain areas than traditional approaches, which the authors suggest are prone to conservative Type II errors.
bioRxiv (Cold Spring Harbor Laboratory)
September 23, 2019
Kirsten C. S. Adam, Manoj K. Doss, Elisa Pabon et al.
2 citations
preprint
THC, the main psychoactive component in cannabis, impairs visual working memory—the ability to temporarily hold visual information in mind. Two double-blind, randomized crossover experiments with 23 healthy adults each found that oral THC (7.5 or 15 mg) reduced working memory performance, increased self-reported mind wandering, and decreased metacognitive accuracy about ongoing task performance. The authors also showed that short task durations and small sample sizes reduce the likelihood of detecting such drug effects.
bioRxiv (Cold Spring Harbor Laboratory)
June 16, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Gorka Zamora-López et al.
1 citation
Psilocybin and the conventional antidepressant escitalopram produce opposite changes in the brain's hierarchical non-equilibrium dynamics when treating major depressive disorder. Using resting-state fMRI before and after treatment, researchers built whole-brain models and measured how much each patient's brain activity deviated from the fluctuation-dissipation theorem. Baseline measures distinguished treatment responders from non-responders within each group. The deviation from the fluctuation-dissipation theorem may serve as a marker to differentiate the brain effects of psilocybin and escitalopram, contributing to understanding how these treatments work for depression.
bioRxiv (Cold Spring Harbor Laboratory)
March 24, 2026
Kenneth Shinozuka, Mattia Rosso, Anna Chaiken et al.
1 citation
A single dose of the atypical psychedelic ibogaine can be highly effective at treating PTSD in veterans up to twelve months later, according to an observational study of 30 veterans. Using a novel EEG analysis method, researchers found that ibogaine shifted high-beta (24 and 25 Hz) brain networks from frontal areas toward posterior regions, an effect seen both three to four days and one month after treatment. This posterior shift correlated with improvements in PTSD symptoms and was replicated in an independent dataset on ibogaine for opioid use disorder. Neural modeling suggested the shift reflects increased corticocortical, not corticothalamic, connectivity. The reconfiguration of high-beta networks may be a robust biomarker for ibogaine's therapeutic effects.
bioRxiv (Cold Spring Harbor Laboratory)
February 18, 2026
Ethan Grove, Trevor Hewitt, Anil K. Seth et al.
1 citation
Visual hallucinations (VHs) occur in psychedelic states and various psychiatric and neurological conditions, but their phenomenology is hard to characterize due to a lack of large-scale datasets. Stroboscopic light stimulation (SLS) with closed eyes reliably induces VHs in healthy people, producing vivid colors and dynamic geometric patterns similar to simple VHs in other contexts. Researchers developed an unsupervised computer-vision pipeline to analyze 10,598 drawings made after hallucination-inducing SLS at a public installation. Most drawings contained geometric forms, consistent with prior observations, but novel patterns like concentric squares, crosses, and hyperbolic shapes also appeared. The pipeline organized the drawings into interpretable classes, mapping the diversity of simple geometric VHs and placing new constraints on theoretical accounts.
bioRxiv (Cold Spring Harbor Laboratory)
January 29, 2026
Venkatesh Subramani, Timothy Nest, Annalisa Pascarella et al.
1 citation
LSD alters brain activity by increasing alpha and beta brain-wave frequencies while genuinely reducing oscillatory power, with these effects showing distinct cortical patterns. The drug also flattens the aperiodic 1/f spectral slope and increases neural signal fractality and complexity, particularly in sensory, language, emotion, and imagery-related networks, while sparing motor cortex. Machine learning identified peak-frequency shifts, aperiodic parameters, and complexity measures as key discriminators of the psychedelic state. Music did not amplify these neural signatures and showed a trend toward attenuation. These findings provide a comprehensive account of how LSD reorganizes large-scale human brain dynamics.
bioRxiv (Cold Spring Harbor Laboratory)
December 9, 2025
Maria Niedernhuber, Dila Suay, Michael J Mueller et al.
1 citation
Classic serotonergic psychedelics strongly alter conscious awareness, but how they change the temporal structure of brain activity has been unclear. In a double-blind, placebo-controlled study with 25 participants using high-density EEG, an ayahuasca-inspired formulation (intranasal N,N-DMT and buccal harmine) accelerated neural dynamics: microstate duration decreased and state transitions became more frequent. Surprisingly, the sequence of microstates became less random, showing higher first-order Markov structure. This restructuring involved reduced transitions into one state (M2) and increased prevalence and accessibility of two others (M3 and M5). The psychedelic state thus produces a syntactically reconfigured, highly metastable neural dynamic, not mere randomization.
bioRxiv (Cold Spring Harbor Laboratory)
November 1, 2025
Dasha Anderson, Justyna K. Hinchcliffe, Megan N. Jackson et al.
1 citation
preprint
Antidepressant doses used in conventional rodent models of depression often exceed those used in clinical practice by 1.5 to 25 times, potentially engaging mechanisms irrelevant to human therapeutic effects. A review of forced swim test studies found median doses of 10 mg/kg across antidepressants, while the more recently developed affective bias test showed doses closer to clinical levels. In a separate analysis of 232 ketamine and 202 fluoxetine rodent studies, median doses were also 10 mg/kg, exceeding animal equivalent doses by 1.6–6.5 times. This mismatch may explain why positive preclinical results often fail to translate into clinical efficacy.
bioRxiv (Cold Spring Harbor Laboratory)
October 14, 2025
Nicholas Kolbman, Amanda Nelson, Rachel Summerfield et al.
1 citation
preprint
Psilocybin and DMT, two serotonergic psychedelics, delay the onset of slow-wave sleep and REM sleep, and cause a short-lasting increase in wakefulness and decrease in slow-wave sleep in rats. Psilocybin also reduces REM sleep, decreases theta power and coherence, and increases high gamma power and coherence during wake and slow-wave sleep, as well as increasing high gamma coherence during REM sleep. DMT increases gamma coherence only during wakefulness. The enhanced high gamma functional connectivity suggests that psychedelic-induced changes in neural dynamics can occur independently of arousal states.
bioRxiv (Cold Spring Harbor Laboratory)
October 3, 2025
Marian Martínez-Marín, Jakub Vohryzek, Anira Escrichs et al.
1 citation
preprint
Consciousness levels after coma can be assessed by measuring how far the brain's dynamics are from equilibrium. Using fMRI data and individualized whole-brain models, researchers found that patients with disorders of consciousness—those in a minimally conscious state or unresponsive wakefulness syndrome—show brain activity closer to equilibrium than healthy controls, with the shift increasing as consciousness decreases. Disruptions in hierarchical drive were identified in default-mode network regions and subcortical hubs like the thalamus. Recovery of near-control hierarchy in the visual network distinguished minimally conscious from unresponsive patients, while limbic areas showed similar abnormalities in both groups. Deviation from the fluctuation-dissipation theorem offers a model-based biomarker for clinical stratification.
bioRxiv (Cold Spring Harbor Laboratory)
June 28, 2025
Jessica Palmieri, Valentina Elce, Monika Schönauer
1 citation
preprint
Emotional intensity in dreams increases as the night progresses, with late-night dreams rated as more emotional than those from early sleep. This pattern was observed in a multiple awakening study of 20 participants who provided 61 dream reports. Contrary to expectations, the rise in emotionality was not tied to REM sleep awakenings. Late-night dream reports were also longer, but report length did not correlate with emotional intensity, suggesting that emotionality is independent of recall ability or narrative complexity. The findings indicate that emotional processing during sleep may unfold across the night through mechanisms separate from those governing dream recall or story elaboration.
bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2025
Prakash Shrimali, Arun Sasidharan, Saketh Malipeddi et al.
1 citation
preprint
Meditation involves training attention inward, but the brain activity that distinguishes meditative from non-meditative states across different traditions is not well understood. Analyzing high-density EEG data from 170 participants—121 advanced meditators and 49 controls—across Vipassana, Brahma Kumaris Raja Yoga, Heartfulness, and Isha Yoga traditions, researchers used random forest classifiers to distinguish meditative from non-meditative states with 91% accuracy. Nonlinear features contributed most, indicating a core neurodynamic profile. Classification was higher in advanced meditators (92%) than controls (85%), with different feature importance: nonlinear and aperiodic features dominated in meditators, while oscillatory and timescale features dominated in controls. Each tradition showed distinct neurodynamic profiles, suggesting multiple pathways lead to meditative states.
bioRxiv (Cold Spring Harbor Laboratory)
June 5, 2025
Ekaterina Shatalina, Natalie Ertl, Kat Petrilli et al.
1 citation
preprint
Inhaling cannabis with THC alone or THC plus CBD reduces resting-state functional connectivity in brain networks that are rich in CB1 and CB2 cannabinoid receptors. Co-administering CBD with THC produced more widespread reductions than THC alone, affecting regions involved in cognition and emotion such as the prefrontal cortex, cingulate cortex, insula, hippocampus, amygdala, and putamen. Higher THC levels in the blood were linked to greater connectivity decreases when CBD was also present. Subjective drug effects correlated with connectivity changes in a region-specific way. The findings suggest that CBD may enhance rather than dampen THC's effects on brain connectivity, contrary to some earlier expectations.
bioRxiv (Cold Spring Harbor Laboratory)
May 21, 2025
Valentina Elce, Giorgia Bontempi, Serena Scarpelli et al.
1 citation
preprint
Dreams are shaped by both stable individual traits and major external events. A large adult cohort provided dream and wakefulness reports alongside demographic, psychometric, cognitive, and sleep measures. Natural language processing revealed semantic features that distinguish dream from wakefulness reports, with this distinction significantly modulated by individual-specific factors. Longitudinal and cross-sample analyses showed that the COVID-19 pandemic left lasting traces on dream content. The findings highlight a dynamic interplay between personal characteristics and external events in shaping dream experiences, offering insights into the cognitive and emotional architecture of dreaming.
bioRxiv (Cold Spring Harbor Laboratory)
April 21, 2025
Shikha Prashad, Andrew Paek, Lisa R. Fournier
1 citation
preprint
Chronic cannabis use is linked to cognitive impairment, but its effect on implicit motor learning—the unconscious acquisition of movement sequences—was unclear. In a study of 30 regular cannabis users and 32 non-users, implicit motor learning occurred in both groups, but longer cannabis use was associated with a smaller learning index and increased beta and gamma EEG activity during rest. Cannabis users also showed reduced visuospatial short-term and working memory on the Corsi block-tapping test. The authors suggest chronic cannabis use may disrupt corticostriatal pathways, impairing implicit motor learning through increased cortical noise.
bioRxiv (Cold Spring Harbor Laboratory)
February 8, 2025
Marco Aqil, Gilles De Hollander, Nina Vreugdenhil et al.
1 citation
preprint
Psilocybin changes how the brain processes visual context, altering perception of the Ebbinghaus illusion and reducing contextual modulation in cortical responses. A computational model links these perceptual and neural changes, suggesting that psychedelics may act by disrupting contextual computations throughout the brain.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2024
Jakub Vohryzek, Morten L. Kringelbach, Edmundo Lopez-Sola et al.
1 citation
preprint
Both psychedelic states and reduced states of consciousness flatten the brain's functional hierarchy, yet their behavioral and phenomenological profiles differ. To resolve this paradox, researchers defined hierarchy by the brain's proximity to thermodynamic equilibrium and examined changes induced by three serotonergic psychedelics: psilocybin, LSD, and DMT. All three consistently reduced the functional hierarchy globally. Unlike loss of consciousness, psychedelics moved the brain toward equilibrium while increasing neural activity complexity, indicating a distinct mechanism involving altered configuration and differentiation of resting-state networks. This work demonstrates how statistical mechanics metrics can characterize different global brain states, advancing understanding of consciousness as an emergent collective process.