Psilocybin may trigger long-lasting antidepressant effects by altering neuron firing, not creating new connections
A rat study shows a single dose of psilocybin yields antidepressant-like behavior lasting at least 12 weeks, without lasting spine growth; instead, lasting functional changes in neuron firing (increased excitability and depolarized readiness) in the medial prefrontal cortex likely underlie the effect, with similar results from the 5-HT2A-targeting drug 25CN-NBOH, implicating this receptor; study notes limitations and cautions about translating to humans.