Journal of Psychopharmacology
January 6, 2026
Connor J. Maltby, Adam K. Klein, Enya Paschen et al.
3 citations
Psilocybin produces rapid and sustained antidepressant effects in major depressive disorder, but the underlying neurobiological mechanisms are unclear. In mice, psilocybin caused dose-dependent occupancy of the 5-HT₂A receptor in the prefrontal cortex, with an inverted-U dose-response for head twitch behavior peaking between 44% and 62% receptor occupancy. A 1.5 mg/kg dose increased time spent in open areas of the elevated zero maze, indicating reduced anxiety, while 3 mg/kg reduced immobility in the forced swim test, suggesting antidepressant-like effects. Both doses shifted α-tubulin post-translational modifications toward more dynamic microtubules and selectively increased synaptic protein expression in the prefrontal cortex, but not the amygdala. These findings indicate that psilocybin's therapeutic effects may involve dose- and region-specific enhancement of neuronal plasticity, with distinct signatures for anxiolytic-like and antidepressant-like properties.
Journal of Psychopharmacology
October 16, 2025
Gerard J. Marek, Soma Makai‐bölöni, Daniel Umbricht et al.
2 citations
A single intravenous dose of GM-2505, a novel 5-HT2A receptor agonist, was safe and well tolerated in 48 healthy volunteers at doses up to 20 mg. The drug produced mild, transient increases in blood pressure and pulse, no significant electrocardiograph changes, and a half-life of 40–50 minutes. Dose-dependent effects appeared on neuroendocrine hormones, neuropsychological and neurophysiological measures, subjective drug effects, and resting-state electroencephalography, with decreased theta and alpha power and increased slow and fast gamma power. These pharmacodynamic effects resembled those of other 5-HT2A agonists, but GM-2505's shorter duration of cardiovascular and subjective effects than psilocybin and longer than DMT suggests a more practical temporal profile for supervised clinical use, with an optimal dose range of 10–15 mg IV.
The Journal of neuroscience : the official journal of the Society for Neuroscience
December 6, 2017
Hsin-Yi Kao, Dino Dvořák, Eunhye Park et al.
The psychotomimetic drug phencyclidine (PCP) impairs a learned hippocampus-dependent place avoidance behavior in rats, even when injected directly into the dorsal hippocampus. PCP increases 60-100 Hz gamma oscillations in hippocampal CA1, and these increases correlate with cognitive impairment. PCP disrupts the coordination between theta-modulated medium-frequency and slow gamma oscillations, and it disrupts the subsecond temporal organization of discharge among place cells, causing ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings indicate that PCP-induced cognitive impairments arise from neural discoordination, specifically excitation-inhibition discoordination, rather than from disruption of place fields themselves.