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Dinesh Pal

Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA. dineshp@umich.edu.

11 papers in the library · 60 citations · publishing 2023-2025

Papers

Intravenous psilocybin attenuates mechanical hypersensitivity in a rat model of chronic pain

Current Biology December 1, 2023 Nicholas Kolbman, Tiecheng Liu, Peter Guzzo et al. 21 citations

A single intravenous dose of psilocybin reduces mechanical hypersensitivity for 28 days in a rat model of formalin-induced chronic pain, suggesting potential for treating chronic pain conditions. The study addresses a gap in research on psilocybin's effectiveness for chronic pain, as prior work focused on psychiatric disorders and substance abuse. No systematic investigation had previously examined psilocybin's impact on chronic pain indices.

Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N-Dimethyltryptamine in Rats.

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.

Intravenous psilocybin induces dose-dependent changes in functional network organization in rat cortex

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.

Consciousness and the Dying Brain.

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.

Regulation of REM and NREM Sleep by Preoptic Glutamatergic Neurons.

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.

Psychedelic-mediated Reversal of General Anesthesia and Restoration of Brain Dynamics in Rat

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.

Psilocybin induces dose-dependent changes in functional network organization in rat cortex

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.

Intravenous Administration of Serotonergic Psychedelics Produce Short-lasting Changes in Sleep-Wake Behavior and High Gamma Functional Connectivity in Rats

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.

Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -Dimethyltryptamine in Rats

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.

Effect of Intravenous Delivery of N,N Dimethyltryptamine on Sleep-Wake States in Rat

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.

Intravenous psilocybin administration attenuates mechanical hypersensitivity in a rat model of chronic pain

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.