A single psychedelic dose of psilocybin increases synaptic density and temporarily reduces serotonin 2A receptor density in the pig brain. One day after injection, hippocampal synaptic vesicle protein 2A (SV2A) density was 4.42% higher, while hippocampal and prefrontal cortex 5-HT2AR density dropped by 15.21% to 50.19%. Seven days later, SV2A density remained significantly higher in the hippocampus (+9.24%) and prefrontal cortex (+6.10%), but 5-HT2AR density had returned to baseline. These persistent synaptic changes and acute receptor down-regulation may underlie psilocybin’s antidepressant effects.
A single dose of psilocybin given to awake female pigs caused behavioral changes—headshakes, scratching, and rubbing—lasting about 20 minutes. The dose produced a 67% occupancy of cerebral 5-HT2A receptors and plasma psilocin levels comparable to those in humans during an intense psychedelic experience. One day after injection, 19 genes in the prefrontal cortex were differentially expressed; after one week, only 3 genes were. Gene set enrichment analysis showed multiple immunological pathways were regulated one week after exposure. The authors suggest that any effects on gene expression are very modest, providing a framework for future research into the lasting molecular mechanisms of a single psilocybin dose.