bioRxiv : the preprint server for biology
February 15, 2025
Nicolas G. Glynos, Emma R. Huels, Amanda Nelson et al.
11 citations
preprint
Intravenous DMT in rats caused dose-dependent increases in serotonin and dopamine in the medial prefrontal and somatosensory cortices, along with changes in brain wave patterns: reduced theta and low gamma power, increased delta, medium gamma, and high gamma power, and altered functional connectivity. All doses produced head twitch responses, most after the low dose. For the first time, endogenous DMT was measured in these cortical sites at levels comparable to serotonin and dopamine, suggesting a physiological role for the compound. The findings point to shared mechanisms with other psychedelics and support DMT's potential for treating psychiatric disorders.
Anesthesiology
September 21, 2013
Eduardo E. Icaza, George A. Mashour
11 citations
The neural mechanisms underlying the psychedelic experience remain poorly understood. A recent neuroimaging study found that psilocybin decreases cerebral blood flow and causes functional disconnections in the brain, a pattern surprisingly similar to that produced by general anesthetics. This article reviews historical instances of psychedelic experiences triggered by anesthetics and compares how these two drug classes produce altered states of consciousness.
Translational Psychiatry
March 25, 2025
Brian H Silverstein, Nicholas Kolbman, Amanda Nelson et al.
8 citations
Psilocybin alters brain network organization in rats in a dose-dependent manner. Using electroencephalography from 27 cortical sites in 12 rats, the study found that psilocybin disrupted theta-gamma coupling, increased frontal high gamma connectivity and network density, and increased posterior theta connectivity and density. Medium gamma frontoparietal connectivity and behavioral activity showed an inverted-U relationship with dose. These results suggest that high-frequency network organization, decoupled from local theta-phase, may be a key signature of psilocybin-induced altered states of consciousness.
Anesthesiology
June 1, 2024
George A. Mashour, UnCheol Lee, Dinesh Pal et al.
8 citations
Near-death experiences have been reported since antiquity and often involve perceptions of light, interactions with entities, and life recall. After in-hospital cardiac arrest, such experiences occur in 10 to 20% of cases. Recent neurophysiologic evidence suggests a surge of gamma oscillations and increased cortical connectivity following cardiac and respiratory arrest, offering a biological basis for this conscious experience.
Commun Biol
December 19, 2023
Rui Dai, Zirui Huang, Tony E. Larkin et al.
7 citations
At concentrations that produce psychedelic effects, nitrous oxide reduces the functional differentiation—the distinctness of activity patterns—within frontoparietal and somatomotor cortical networks. This suggests that the gas alters brain network organization, potentially contributing to its consciousness-altering properties. The finding points to a neural mechanism underlying the non-ordinary state induced by nitrous oxide, involving reduced specialization of key brain regions.
Sleep
May 26, 2025
Alejandra Mondino, Amir Jadidian, Brandon A Toth et al.
4 citations
The preoptic area of the hypothalamus, long thought to only promote sleep, contains glutamatergic neurons (MLPO_VGLUT2) that actually drive wakefulness and suppress REM sleep. Using fiber photometry in mice, these neurons were highly active during REM sleep, wakefulness, and brief arousals, but minimally active during non-REM sleep. Chemogenetic stimulation of MLPO_VGLUT2 inhibited REM sleep onset, independent of non-REM fragmentation caused by hypothermia, and blocked the REM sleep rebound normally seen after total sleep deprivation. Chemogenetic inhibition increased REM sleep time only during the light phase. Mapping showed these neurons project to brain regions that promote wakefulness and inhibit REM sleep. The authors conclude that MLPO_VGLUT2 powerfully suppress REM sleep, and their overactivation disrupts REM recovery.
bioRxiv Preprint Server
January 22, 2025
Emma R. Huels, Nicholas Kolbman, Christopher W Fields et al.
4 citations
preprint
A serotonergic psychedelic, DOI, can reverse general anesthesia and restore wakefulness in rats, even while anesthetics like propofol or isoflurane continue to be delivered. Behavioral arousal was accompanied by recovery of high gamma functional connectivity and restoration of brain network structure. These effects were blocked by a 5-HT2A antagonist, volinanserin, and a non-psychedelic 5-HT2A agonist, lisuride, failed to produce similar results. This provides the first evidence of psychedelic-mediated reversal of general anesthesia and concurrent restoration of brain dynamics associated with normal wakefulness.
bioRxiv (Cold Spring Harbor Laboratory)
February 12, 2024
Brian H Silverstein, Nicholas Kolbman, Amanda Nelson et al.
3 citations
preprint
Psilocybin disrupts the coupling between theta and gamma brain waves in rats and reorganizes brain networks in a dose-dependent manner. Using 27 electrodes across the cortex, the study found that psilocybin increased frontal high gamma connectivity and posterior theta connectivity, as well as network density in those regions. Medium gamma frontoparietal connectivity showed a nonlinear relationship with dose. Theta-gamma phase-amplitude coupling was disrupted. These changes suggest that high-frequency network organization, decoupled from local theta-phase, may be a signature of the altered state of consciousness induced by psilocybin.
JAMA Psychiatry
June 1, 2026
Ben Deverett, Duan Li, Theresa R. Lii et al.
1 citation
Ketamine produces distinct brain-wave patterns that may be linked to its therapeutic effects. General anesthesia selectively blocks one of these patterns—theta oscillations—while leaving another pattern, beta-gamma oscillations, intact. In 52 participants, ketamine given during anesthesia preserved beta-gamma power increases but eliminated the characteristic theta augmentation seen during awake administration. This suggests that different neurophysiologic effects of ketamine can be separated, offering a way to investigate which brain-wave changes underlie its antidepressant, analgesic, or dissociative properties.
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Niloufar Pouyan, Jacob S. Aday, Steven E. Harte et al.
1 citation
People with treatment-resistant conditions often see their illness as part of their identity. The pictorial representation of illness and self measure (PRISM) gauges this self-condition enmeshment. In a survey of 297 individuals who used psychedelics therapeutically on their own, most reported symptom improvement: 95.4% with depression, 98.36% with posttraumatic stress disorder, and 94.87% with anxiety. PRISM scores dropped significantly after the most salient psychedelic experience, indicating reduced identification with the condition. The decrease in PRISM scores correlated with symptom improvement across all conditions. PRISM appears useful for tracking how psychedelics affect self-perception across diagnoses, though limitations include convenience sampling, potential positive bias, and retrospective reporting.
bioRxiv : the preprint server for biology
October 23, 2024
Rui Dai, Hyunwoo Jang, Anthony G. Hudetz et al.
1 citation
preprint
Consciousness appears to depend on global interactions across multiple brain regions rather than on localized neural activity. Using fMRI data across psychedelic, sleep, and deep sedation states, the study found a mirror-image pattern: psychedelic states increased global functional connectivity and decreased local neural synchrony, while non-REM sleep and deep sedation showed the opposite pattern. This pattern was observed in anterior-posterior and posterior-posterior brain regions but not within the anterior brain alone. Anterior transmodal regions were key for anterior-posterior connectivity, while posterior transmodal and unimodal regions were critical for posterior-posterior connectivity. The findings support global theories of consciousness and bridge the Global Neuronal Workspace hypothesis and Integrated Information Theory by showing shared neural mechanisms.
bioRxiv : the preprint server for biology
June 1, 2026
Panagiotis Fotiadis, Hyunwoo Jang, Rui Dai et al.
Brain waves coordinate neural communication and shape conscious perception. Analyzing blood oxygen level-dependent activity from the Human Connectome Project and other datasets across sleep, propofol anesthesia, and psychedelic states (LSD, DMT, psilocybin, nitrous oxide, ketamine), four dominant wave propagation motifs were identified: a global synchronized wave, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave.
Journal of Neuroscience
December 19, 2025
Nicolas G. Glynos, Emma R. Huels, Trent Groenhout et al.
In rats, intravenous DMT causes dose-dependent increases in serotonin and dopamine in the medial prefrontal and somatosensory cortices, along with distinct changes in brain wave patterns: reduced theta and low gamma power, increased delta, medium gamma, and high gamma power, and altered functional connectivity. Head twitch responses were most frequent at the lowest dose. Endogenous DMT was detected in the cortex of most animals at baseline, suggesting it may be naturally present. The work provides a detailed neurochemical and neurophysiological profile of DMT action in rats.
medRxiv Preprint Server
December 16, 2025
Derek Newman, Charlotte Maschke, George A. Mashour et al.
preprint
Propofol anesthesia can cause either the expected suppression of brain activity or a transient paradoxical excitation. EEG measures of signal complexity and entropy, specifically Type I and Type II complexity on the Complexity–Entropy Causal Plane (CECP), distinguish these divergent neural trajectories. The findings suggest that paradoxical excitation is reflected in both types of complexity, that the CECP separates excitation from suppression, and that baseline EEG complexity is linked to how susceptible a person is to propofol.
bioRxiv
November 26, 2025
Rui Dai, Rodrigo Cofré, Christopher Timmermann et al.
preprint
Classical psychedelics (DMT, LSD, psilocybin) and non-classical ones (nitrous oxide, ketamine) all disrupt local synchrony in small brain regions (<1 cm³) in humans, as measured by functional magnetic resonance imaging. This disruption occurred extensively in cortical regions and sparsely in subcortical regions. As local synchrony declined, large-scale functional connectivity increased. For classical psychedelics, the disruption was most strongly associated with 5-HT receptors; for nitrous oxide and ketamine, it was most strongly associated with NMDA receptors. Both neuronal and non-neuronal cell types were linked to these changes. The findings suggest diverse molecular events converge on a common outcome of disrupted local synchrony, which then mediates drug-specific global connectivity changes.
medRxiv
August 7, 2025
Ben Deverett, Duan Li, Theresa R. Lii et al.
preprint
Ketamine produces dissociative, analgesic, and antidepressant effects, but it is unclear whether its underlying neurophysiological signatures can be separated. In this observational cohort study, 52 participants (healthy volunteers, elective surgery patients, and patients with depression) received a subanesthetic infusion of ketamine or placebo, with or without general anesthesia. When ketamine was given under general anesthesia, its characteristic low-frequency brain wave augmentation was absent, while high-frequency power modulation was preserved. This selective modulation suggests a method for investigating the distinct roles of high- and low-frequency neural activity in ketamine's behavioral effects.
Universität Zürich, ZORA
May 1, 2025
Niloufar Pouyan, Jacob S. Aday, E Harte, Steven et al.
After naturalistic psychedelic use, people with depression, PTSD, or anxiety reported reduced identification of their identity with their illness, as measured by the pictorial representation of illness and self measure (PRISM). Among 297 individuals, the majority in each condition reported symptom improvement: 95.4% with depression, 98.36% with PTSD, and 94.87% with anxiety. PRISM scores significantly decreased after the most salient psychedelic experience, and larger reductions in self-condition enmeshment were associated with greater symptom improvement. The findings suggest PRISM can detect changes in self-perception across conditions, though limitations include retrospective reporting and unclear dosing.
November 4, 2024
Jacob S. Aday, Jenna McAfee, Deirdre A. Conroy et al.
preprint
In a small open-label proof-of-concept trial, five adults with fibromyalgia received two doses of psilocybin (15 mg and 25 mg) two weeks apart, along with psychotherapy sessions. No serious adverse events occurred; transient blood pressure or heart rate elevations during dosing resolved by the end of treatment, and four of five participants had temporary headaches. One month after the second dose, participants reported clinically meaningful improvements in pain severity, pain interference, and sleep disturbance. One participant rated their symptoms as very much improved, two as much improved, and two as minimally improved. Improvements were also seen in fibromyalgia symptoms, anxiety, and fatigue. The findings suggest psilocybin-assisted therapy is well-tolerated and warrants larger randomized controlled trials.
Physiology
May 1, 2024
Rachel Summerfield, Trent Groenhout, Tiecheng Liu et al.
Intravenous DMT, a psychedelic, increases wakefulness and reduces slow-wave sleep in rats during the first three hours after administration, with a delay in the onset of rapid eye movement sleep. Low (3.75 mg/kg) and high (7.5 mg/kg) doses both produced these effects, while time spent in REM sleep during the light period was unaffected. The findings align with previous reports on serotonergic psychedelics and wakefulness.
bioRxiv (Cold Spring Harbor Laboratory)
August 28, 2023
Nicholas Kolbman, Tiecheng Liu, Peter R. Guzzo et al.
preprint
A single intravenous dose of psilocybin (1 mg/kg or 10 mg/kg) reduced mechanical hypersensitivity in rats for 28 days after formalin-induced chronic pain, but had only a limited effect on thermal hyperalgesia. Formalin injection caused thermal hyperalgesia and bilateral mechanical hypersensitivity in all rats. Psilocybin significantly attenuated the mechanical hypersensitivity throughout the 28-day testing period, while thermal hyperalgesia was reduced only on days 1, 3, 5, and 21. These results suggest psilocybin may have potential for treating chronic pain, though its effects on different pain types vary.
Science Translational Medicine
February 22, 2012
George A. Mashour
The psychedelic drug psilocybin disrupts the coordinated activity of important brain regions, which may help explain its potential for treating psychiatric disorders. This uncoupling of brain area activity offers clues for developing new therapies.
Current biology : CB
July 2, 2026
Youngjai Park, Younghwa Cha, Hyoungkyu Kim et al.
The human brain's information flow alternates between two dominant modes roughly every 200 milliseconds: a top-down mode where anterior brain regions drive posterior activity, and a bottom-up mode with reverse directionality. These sub-second alternations are most prominent during wakefulness, gradually diminish under anesthesia, and show pathological imbalance in attention-deficit/hyperactivity disorder (ADHD). Simultaneous EEG-fMRI recordings reveal that top-down dynamics coincide with increased activity in higher-order cognitive networks, while bottom-up dynamics correspond to heightened sensory network activity. A connectome-based coupled-oscillator model reproduces these transitions, suggesting they emerge naturally from structural connectivity. Relative phase analysis (RPA) enables tracking these whole-brain dynamics with millisecond precision in real time from electroencephalography.
Research Square
January 12, 2026
Niloufar Pouyan, Chelsea M Kaplan, Tony E. Larkin et al.
Subanesthetic nitrous oxide (N2O) alters visual experience by reconfiguring large-scale brain networks rather than changing early visual processing. In a placebo-controlled fMRI study with 13 healthy adults, participants viewed a flashing checkerboard and rated visual intensity and unpleasantness. Increased unpleasantness under N2O was linked to reduced connectivity between the right anterior insula and the anterior cingulate cortex and lateral occipital cortex. Network analyses revealed reduced modularity and a collapse of hierarchical organization, with sensorimotor connectivity redistributed toward salience and associative networks. These findings suggest that altered visual experience under N2O arises from disrupted salience integration and increased cross-network communication.
bioRxiv : the preprint server for biology
March 28, 2025
Youngjai Park, Younghwa Cha, Hyoungkyu Kim et al.
preprint
The human brain shifts between two directional modes on a sub-second timescale: a top-down mode where anterior regions drive posterior activity and a bottom-up mode with reverse directionality. These shifts are most distinct during full consciousness and become less pronounced as awareness fades. Simultaneous EEG-fMRI recordings show the top-down mode coincides with higher-order cognitive network activity, while the bottom-up mode aligns with sensory system activity. An inattentive ADHD cohort exhibited imbalances in these transition dynamics compared to typically developing individuals. A coupled-oscillator model of the structural brain network reproduced these patterns, suggesting they arise naturally from inter-regional neural interactions.
Nature Communications
October 24, 2024
Hyunwoo Jang, George A. Mashour, Anthony G. Hudetz et al.
A metric called the integration-segregation difference (ISD), derived from fMRI data, captures two key brain network properties: efficiency (integration) and clustering (segregation). During anesthesia with propofol, brain networks shift profoundly toward segregation as consciousness is lost. A common sequence of disintegration and reintegration occurs in unimodal and transmodal networks during loss and return of responsiveness. Machine learning models using these measures accurately identify awake versus unresponsive states. Metastability is more closely linked to integration, while complexity is linked to segregation. Similar patterns appear in sleep. The ISD reliably indexes states of consciousness.