medRxiv Preprint Server
September 10, 2024
Kristin Dawson, Athena May Jean M. Carangan, Jessica Klunder et al.
4 citations
preprint
Depression and PTSD are linked to poor health outcomes similar to aging. Ketamine infusions rapidly reduce symptoms of treatment-resistant depression and PTSD. In 20 participants with moderate to severe depression or trauma, a 2-3 week course of 0.5 mg/kg ketamine infusions reduced depression and PTSD scores. Epigenetic age, measured by OMICmAge, GrimAge V2, and PhenoAge biomarkers, decreased after treatment. Changes in underlying epigenetic biomarker proxies and surrogate protein markers were also observed. The findings align with prior research on ketamine's epigenetic effects and suggest these biomarkers capture signals related to clinical improvement and biological aging.
bioRxiv Preprint Server
July 3, 2025
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
1 citation
preprint
Psychedelic 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.
Translational Psychiatry
July 11, 2026
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
Ketamine and MDMA, compounds known as psychoplastogens, show therapeutic potential for mood and trauma-related disorders, but their molecular mechanisms are not fully understood. In a study analyzing blood samples from 20 ketamine-treated participants and saliva samples from 16 MDMA-treated participants, DNA methylation changes were examined using a Brain-Epigenome-Wide Association Study targeting brain-relevant genes. Ketamine was associated with 405 significantly altered genes and 169 functional networks, while MDMA was linked to 346 altered genes and 183 networks. Both compounds converged on pathways related to neuroplasticity and neuroimmune regulation, suggesting they induce peripheral epigenetic changes that engage molecular pathways relevant to psychiatric health.