5mC and 5hmC Detection Highlights How Psychedelics Affect Brain Epigenetic Patterns
Zenodo (CERN European Organization for Nuclear Research) November 4, 2025 Bertocchi, Uri, Schwartz, Amit, Umschweif, Gali et al.
Psilocybin, a serotonergic psychedelic, produces long-lasting antidepressant effects, but the underlying mechanisms are not fully understood. This study examined epigenetic changes in the mouse brain after psilocybin treatment. Male C57BL/6 mice received either psilocybin or saline, and after 72 hours, DNA from the prefrontal cortex was analyzed using nanopore sequencing. The results showed 1,404 regions with altered 5-hydroxymethylcytosine (5hmC) levels, strongly enriched in the glutamatergic synapse pathway. In contrast, only 51 regions of altered 5-methylcytosine (5mC) were found, with no pathway enrichment. These findings suggest that psilocybin rapidly induces epigenetic modifications primarily through 5hmC, which may contribute to its sustained antidepressant effects and offer new targets for treating major depressive disorder.