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.
Frontiers in Systems Neuroscience
December 1, 2021
Minkyung Kim, Hyoungkyu Kim, Zirui Huang et al.
The brain's ability to switch between internal and external modes is crucial for generating models of self and world, and this switching may rely on a state near criticality—a balanced condition between order and disorder. Large synchronization fluctuations of brain networks near criticality create temporal windows that favor either integrating internal information or processing external stimuli. Using computational modeling, EEG, and fMRI analyses across altered states of consciousness, synchronized networks bias toward internal information while incoherent networks bias toward external information. These preferences are most prominent at criticality and in conscious states associated with 4–12 Hz bandwidth.
Advances in Consciousness Research
October 28, 2010
Lucas Campos, Adrian Pichurko, George A. Mashour
General anaesthetics rapidly and reversibly stop consciousness, making them a powerful tool for studying the transition between conscious and unconscious states. With 40 million patients in North America alone receiving general anaesthesia each year, the operating room offers a controlled environment to investigate the molecular and cognitive mechanisms underlying consciousness.
Rui Dai, Hyunwoo Jang, Anthony G Hudetz et al.
Across altered states of consciousness, psychedelics and sedatives produce opposite patterns of brain network organization. Psychedelics increase large-scale integration and reduce segregation of brain network interactions, while sleep and propofol sedation show the opposite pattern. These opposing integration-segregation patterns were consistently observed across multiple measures of functional connectivity, network topology, and interaction complexity, and reliably differentiated conscious states in an unbiased, data-driven manner. The findings demonstrate that psychedelic and sedated states are characterized by systematic and opposing shifts in large-scale brain organization.