Scientific Reports
July 26, 2022
Caroline T. Golden, Paul Chadderton
45 citations
Psilocybin, a hallucinogenic compound being investigated for treating depression and PTSD, alters neural activity in the anterior cingulate cortex of awake mice. Using multi-unit recordings, the study found that psilocybin (2 mg/kg) significantly decreased low-frequency local field potential power while gamma activity trended upward. Overall population firing rates increased, with nearly half of individual neurons showing a significant increase. Psilocybin reduced phase modulation of cells across most frequency bands, indicating desynchronization of cortical populations. Bursting behavior changed in a subset of cells, and neurons that increased burst firing often transitioned from a phase-modulated to an unmodulated state. These effects suggest disruption of top-down processing and dissolution of the default mode network in the acute psychedelic state.
Psychedelic Medicine
February 3, 2026
Anton T. Gregersen, Tobias Whelan, Caroline T. Golden et al.
2 citations
Psilocybin, a serotonergic psychedelic, impaired short-term learning and unlearning speeds in rats performing a three-choice visual reversal learning task, though exploratory analysis suggested possible long-term enhancements in learning dynamics. Only five of sixteen Long-Evans rats (31%) successfully completed all six reversal protocols, demonstrating significant learning and unlearning over time. Computational modeling showed low learning rates with no significant differences between psilocybin and placebo conditions on any parameters. The findings indicate a nuanced effect of psilocybin on cognitive flexibility, with potential relevance for its use in neuropsychiatric disorders, but further research is needed on long-term outcomes.
Molecular Psychiatry
August 26, 2025
Ross J. Purple, Rahul Gupta, Christopher W. Thomas et al.
2 citations
After a therapeutically relevant dose of psilocybin, high-frequency oscillations at 100 Hz appear in the infralimbic cortex of rats, lasting about an hour, while overall neuron firing rates and spike-train complexity decrease. These acute effects are stronger when the animal is at rest than during a sustained attention task. Over the following days, power in beta and low-gamma frequencies (20–60 Hz) gradually increases in the infralimbic cortex. The findings point to infralimbic network oscillations as potential markers of psychedelic-induced plasticity that unfold over multiple days, revealing details not easily seen in human brain imaging.
Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Psilocybin and ketamine acutely increased reward responsiveness in rats, and the effect persisted 24 hours after dosing. The increase from psilocybin, but not ketamine, was blocked by a 5-HT2A receptor antagonist. Other psychedelics, DMT and DOI, also acutely increased reward responsiveness but the effect did not last 24 hours. The non-psychedelic 5-HT2A agonist lisuride and the SSRI fluoxetine had no positive effects. These results suggest psychedelics can produce acute and enduring increases in reward responsiveness, partly through the 5-HT2A receptor, though the time course varies and clinical implications require further validation.
bioRxiv (Cold Spring Harbor Laboratory)
March 4, 2026
Matthew D. B. Claydon, Justyna K. Hinchcliffe, Julia M. Bartlett et al.
Psilocybin, the active compound in magic mushrooms, produces rapid and lasting antidepressant effects in people with major depressive disorder, but the underlying brain mechanisms are not fully understood. In rats, psilocin (the active metabolite of psilocybin) alters negative affective biases—a key feature of depression—by acting on a specific circuit in the medial prefrontal cortex. It suppresses excitatory signals to cortico-amygdala projection neurons while enhancing excitatory transmission to other targets, effects dependent on 5HT1A and 5HT2A receptors. These changes persist for at least 24 hours and shift from suppressed excitation to enhanced inhibition in those same cells. Chemogenetically inhibiting these neurons reproduced psilocybin's effects on affective biases and reward memories, identifying this circuit as a key substrate for its antidepressant actions.
February 27, 2025
Anton T. Gregersen, Tobias P. Whelan, Caroline T. Golden et al.
preprint
In a visual reversal learning task with rats, psilocybin temporarily impaired the speed of learning and unlearning, but exploratory analyses suggested possible long-term improvements in learning dynamics. Five out of sixteen rats completed all six reversal protocols, showing significant decreases in sessions needed to meet learning criteria and in reaction time over successive reversals. Computational modeling revealed low learning rates overall, with no significant differences between psilocybin and placebo on any modeled parameter. The findings indicate a nuanced, time-dependent effect of psilocybin on cognitive flexibility, with short-term impairment and hints of later enhancement, warranting further study of long-term outcomes.
Spiral (Imperial College London)
December 1, 2016
Caroline T. Golden
Psilocybin, a serotonergic agonist, shifts the anterior cingulate cortex (ACC) of awake mice into a desynchronized state resembling REM sleep, marked by increased network activation, reduced low-frequency oscillations (delta, theta, alpha), and a moderate rise in gamma power. In a working memory delayed response task, ACC neurons encoded both low-level stimulus information and high-level choice and reward anticipation, with population activity predicting task outcomes faster than behavioral responses. Optogenetic perturbation of ACC neurons during the delay period effectively altered behavior and disrupted neural encoding of working memory information.