Intravenous psilocybin induces dose-dependent changes in functional network organization in rat cortex
Brian H Silverstein, Nicholas Kolbman, Amanda Nelson, Tiecheng Liu, Peter R. Guzzo, Jim Gilligan, UnCheol Lee, George A. Mashour, Giancarlo Vanini, Dinesh Pal
Translational Psychiatry March 25, 2025 DOI: 10.1038/s41398-025-03308-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Male and female rats |
| Intervention | Psilocybin |
| Dose | 0.1, 1, and 10 mg/kg delivered over an hour |
| Topics | Psilocybin |
| Keywords | Psychedelics Brain connectivity Consciousness |
| Citations | 8 |
| Key findings | Psilocybin dose-dependently disrupts theta-gamma coupling and increases frontal high gamma and posterior theta connectivity and network density in rat cortex. |
Abstract
Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in cortical networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on cortex-wide network dynamics. Previous electroencephalographic studies of psychedelics in rodents have primarily used sparse electrode arrays with limited spatial resolution, precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in this study, we used electroencephalographic recordings from 27 sites/electrodes across rat cortex (n = 6 male, 6 female) to characterize the effect of psilocybin (0.1, 1, and 10 mg/kg delivered over an hour) on brain network organization as inferred through changes in node degree (an index of network density) and connection strength (via weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p < 0.05], 2) increased frontal high gamma connectivity [p < 0.05] and posterior theta connectivity [p ≤ 0.049], and 3) increased frontal high gamma [p < 0.05] and posterior theta [p ≤ 0.046] network density. The behavioral activity and the medium gamma frontoparietal connectivity showed an inverted-U relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 12
- Emerging mechanisms of psilocybin-induced neuroplasticity TIPS - Trends in Pharmacological Sciences September 16, 2025
- Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain Neuroscience & Biobehavioral Reviews December 16, 2025
- The entropic brain today Brain December 12, 2025
- The transformational power of psychedelics: catalysts for creativity, consciousness, and mental health. Molecular Psychiatry September 30, 2025
- Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin Molecular Psychiatry August 26, 2025
and 7 more in the library
Cites 35
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
and 30 more in the library