Translational Psychiatry
February 23, 2022
Trevor Sharp, Christopher W. Thomas, Cristina Blanco‐duque et al.
40 citations
Psilocin, a serotonergic psychedelic, alters sleep architecture and cortical activity in mice. Acute administration delays REM sleep onset, reduces NREM sleep maintenance for about three hours, and enhances a 4 Hz EEG oscillation. No long-term changes in sleep-wake quantity occur. Psilocin does not affect the overall homeostatic sleep rebound after sleep deprivation, but it slows the recovery of slow-wave activity in the medial prefrontal and surrounding cortex. These findings suggest psilocin influences both global vigilance state control and local sleep homeostasis, which may relate to its antidepressant effects.
Science Translational Medicine
January 10, 2024
Katie Kamenish, Roberto Arban, Aslihan Selimbeyoglu et al.
26 citations
Negative cognitive biases—where mood colors learning and memory—are a core feature of major depressive disorder, and reversing them may be key to how rapid-acting antidepressants work. In rats, a single dose of ketamine, scopolamine, or psilocybin selectively weakened a negative affective bias induced in an associative learning task. Low doses of ketamine and psilocybin, but not high doses, reversed the valence of the bias 24 hours later. Only psilocybin produced a lasting positive bias that depended on new learning. Ketamine's relearning effects required protein synthesis in the medial prefrontal cortex and could be altered by cue reactivation, pointing to experience-dependent neural plasticity as a shared mechanism for both the rapid and sustained effects of these drugs.
bioRxiv Preprint Server
February 16, 2021
Christopher W. Thomas, Cristina Blanco-Duque, Benjamin Bréant et al.
4 citations
preprint
A single dose of psilocin, the active compound in psychedelic mushrooms, alters sleep architecture in mice. Psilocin delayed the onset of REM sleep and reduced NREM sleep maintenance for about three hours after injection, without causing long-term changes in sleep quantity. The acute brain response featured enhanced oscillations around 4 Hz. When mice were sleep-deprived, psilocin did not change the overall amount of sleep rebound, but it slowed the recovery of slow wave activity in the medial prefrontal cortex. These findings suggest that psilocin affects both global vigilance and local sleep homeostasis, which may relate to its potential antidepressant effects.
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.
bioRxiv (Cold Spring Harbor Laboratory)
December 13, 2024
Ross J. Purple, Rekha Gupta, Christopher W. Thomas et al.
1 citation
preprint
Psilocybin at therapeutically relevant doses (0.3 or 1 mg/kg) in rats unmasked 100 Hz high frequency oscillations in the infralimbic cortex that persisted for about an hour, accompanied by decreased pyramidal cell firing rates and reduced signal complexity. These acute effects were more pronounced during rest than during a sustained attention task. Over the following days, gradually emerging increases in beta and low-gamma (20-60 Hz) power appeared specifically in the infralimbic cortex, suggesting network plasticity on multi-day timescales. The findings implicate infralimbic network oscillations as potential biomarkers of psychedelic action not readily detectable 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.
bioRxiv (Cold Spring Harbor Laboratory)
January 15, 2026
Justyna K. Hinchcliffe, Christopher W. Thomas, Gary Gilmour et al.
Psilocybin, a serotonergic psychedelic, can rapidly and lastingly reverse impaired reward processing in a rat model of depression. In rats with chronic interferon-alpha-induced depression, a single dose of psilocybin (0.3 mg/kg) restored reward-induced behavioral biases within 24 hours, and the effect persisted for at least 7 days. This suggests that restoring blunted reward processing may contribute to psilocybin's sustained antidepressant effects.