Brain-epigenome wide association study (BEWAS) on the effects of two emerging psychedelics: ketamine & MDMA
bioRxiv Preprint Server – July 03, 2025
Source: bioRxiv
Summary
Psychedelics like ketamine and MDMA induce lasting changes in brain gene activity. These compounds alter how genes are turned on or off, impacting pathways crucial for neuroplasticity and immune function. Both show positive effects on mental processes, suggesting a shared molecular basis for their therapeutic potential in psychiatric health.
Abstract
Psychedelic compounds such as ketamine and MDMA have shown therapeutic promise for mood and trauma-related disorders, yet their molecular mechanisms remain unclear. This study applied a Brain-Epigenome-Wide Association Study (BEWAS) to assess DNA methylation changes in brain-enriched genes following treatment. Pre- and post-treatment blood (ketamine, N = 20) and saliva (MDMA, N = 16) samples from clinical trial participants were analyzed. Ketamine altered methylation at 1,210 CpG sites; MDMA affected 2,074 CpG sites. Functional enrichment analyses revealed changes in genes involved in neuroplasticity, immune regulation, and mental processes. Overlapping effects were observed in genes such as PTPRN2 and SHANK2, suggesting shared epigenetic mechanisms in driving increased neuroplasticity. These findings highlight psychedelics’ capacity to induce coordinated, lasting molecular changes relevant to neuroimmune function and psychiatric health.