Psilocybin produces different behavioral and brain-altering effects depending on the dose

Psilocybin dose appears to produce distinct behavioral outcomes and different markers of neuroplasticity in mice, linking receptor engagement to potential anxiolytic versus antidepressant-like effects. In a mouse study, researchers measured 5-HT2A receptor occupancy in the prefrontal cortex and compared it with drug effects on head twitch behavior and later behavioral assays. Moderate dosing was associated with reduced anxiety-like behavior in an elevated maze, while higher dosing produced antidepressant-like effects in a forced swim test. The brain analyses focused on markers of cellular plasticity. Both moderate and high doses increased microtubule dynamics in mood-relevant regions, but increases in synaptic protein markers occurred in the prefrontal cortex only, not the amygdala. The findings support a region-specific response to psychedelic receptor activation and suggest that “stronger” does not necessarily mean “better” for therapeutic outcomes.