Brain-epigenome wide association study (BEWAS) on the effects of two emerging psychedelics: ketamine & MDMA
Moira G. Semple, Sarah E. Mennenga, Ryan Smith, Varun B. Dwaraka, Baruch Rael Cahn, Joseph Tafur, David M. Rabin, Berra Yazar-Klosinski, Candace R. Lewis
bioRxiv Preprint Server July 3, 2025 preprint DOI: 10.1101/2025.07.03.663007 via bioRxiv
Summary
AI-generated from the abstractPsychedelic compounds like ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with ketamine altering 1,210 CpG sites and MDMA affecting 2,074 CpG sites. These changes occur in genes involved in neuroplasticity, immune regulation, and mental processes, with overlapping effects in genes such as PTPRN2 and SHANK2. The findings suggest shared epigenetic mechanisms through which psychedelics may drive increased neuroplasticity and produce lasting molecular changes relevant to neuroimmune function and psychiatric health.
Study at a glance
| Characteristics | Observational cohort |
|---|---|
| Sample size | 36 |
| Population | Clinical trial participants |
| Interventions | Ketamine MDMA |
| Topics | Ketamine MDMA Neuroplasticity |
| Keywords | Psychedelics Psychoactive compounds Entheogens |
| Citations | 1 |
| Key finding | Ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with overlapping effects in genes such as PTPRN2 and SHANK2, suggesting shared epigenetic mechanisms driving neuroplasticity. |
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.