Anesthesiology
May 22, 2013
UnCheol Lee, Seungwoo Ku, Gyu‐jeong Noh et al.
436 citations
Ketamine, like propofol and sevoflurane, inhibits feedback (anterior-to-posterior) connectivity between frontal and parietal brain regions after loss of consciousness, while preserving feedforward (posterior-to-anterior) connectivity. In 30 surgical patients given intravenous ketamine (2 mg/kg), electroencephalography showed that feedback connectivity gradually diminished and was significantly reduced after loss of consciousness (mean baseline 0.0074 vs. anesthesia 0.0055). Feedforward connectivity remained unchanged. Ketamine reduced alpha power and increased gamma power, unlike propofol and sevoflurane. Despite molecular and neurophysiologic differences, diverse anesthetics disrupt frontal-parietal communication, suggesting that directional connectivity analysis could provide a common metric for general anesthesia.
British Journal of Anaesthesia
April 13, 2018
Phillip E. Vlisides, Tarik Bel‐bahar, Amanda Nelson et al.
117 citations
No Summary
Frontiers in Human Neuroscience
March 18, 2021
Emma R. Huels, Hyoungkyu Kim, UnCheol Lee et al.
51 citations
Shamanic practitioners in trance show brain changes that overlap with but are distinct from those caused by psychedelic drugs. In 24 practitioners and 24 controls, EEG recordings during shamanic drumming revealed increased gamma power linked to visual changes, decreased low alpha and increased low beta connectivity, reduced gamma-band signal diversity tied to insightfulness, and increased criticality in beta and gamma bands correlating with complex imagery. Practitioners' altered-state scores matched or exceeded those of people on psychedelics. The findings indicate that shamanic trance and psychedelic states share some phenomenal features but produce unique neural signatures.
Frontiers in Pain Research
March 18, 2025
Jenna McAfee, Avinash Hosanagar, Vijay Tarnal et al.
18 citations
In a small open-label pilot trial, five people with fibromyalgia received two doses of psilocybin (15 mg and 25 mg) along with psychotherapy. The treatment was well-tolerated: there were temporary increases in blood pressure or heart rate during dosing that returned to normal, no serious adverse events, and four of five participants had short-lived headaches. One month after the second dose, participants reported large reductions 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. Recruitment stopped early due to generalizability concerns and changing FDA guidance, but the results suggest psilocybin-assisted therapy is safe for fibromyalgia and warrants larger trials.
bioRxiv (Cold Spring Harbor Laboratory)
October 23, 2023
Tyler G. Ekins, Isla Brooks, Sameer Kailasa et al.
17 citations
preprint
Classic psychedelic drugs, such as LSD and psilocybin, are thought to boost brain cell activity in the prefrontal cortex by activating serotonin 2A receptors. However, this research shows that these drugs actually suppress the intrinsic excitability of pyramidal neurons in a dose-dependent manner. The suppression is stronger when drugs are applied outside cells than inside, and it occurs through a previously unknown mechanism: enhancement of potassium M-current channels, independent of serotonin 2A receptor activation. Computer models reveal that M-current activation interacts with other mechanisms to reduce excitability and shorten working memory span. This suggests psychedelics may trigger widespread homeostatic adjustments that contribute to therapeutic benefits.
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.
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.
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.
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.
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.