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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Sample size | 36 |
| Population | Clinical trial participants |
| Interventions | Ketamine MDMA |
| Topics | Ketamine MDMA Neuroplasticity Esketamine |
| Keywords | Psychedelics Psychoactive compounds Entheogens Hallucinogens Gene expression Gene activity Gene regulation Epigenetics Transcriptional changes Brain function Mental health Psychiatric health Mental processes Therapeutic potential Psychiatric treatment |
| Citations | 1 |
| Key findings | 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.
Comparable studies
Other observational and cohort studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subjective Reports of the Effects of MDMA in a Clinical Setting Individuals who took MDMA in a clinical setting | 1986 | Observational study | |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| The Psychological and Physiological Effects of MDMA on Normal Volunteers Older, more educated, drug-experienced individuals | 1986 | Observational cohort | |
| Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits Young people who were regular or novice MDMA users, or non-users | 1998 | Observational cohort | n = 30 |
Citations in the library
Cites 28
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
and 23 more in the library