Serotonergic psychedelics as epigenetic modulators: A paradigm shift in Alzheimer's disease therapeutics.
Esmaeel G Gojani, Houman Farzin, Robert J Sutherland, Majid Mohajerani
Neuroscience & Biobehavioral Reviews May 1, 2026 DOI: 10.1016/j.neubiorev.2026.106619 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Serotonergic psychedelics |
| Topics | Serotonin |
| Keywords | Alzheimer’s disease Dna methylation Epigenetics Histone acetylation Serotonergic psychedelics |
| Key findings | Targeted engagement of 5-HT2A receptors may help counteract epigenetic abnormalities that contribute to Alzheimer's disease pathogenesis. |
Abstract
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau pathology, synaptic dysfunction, and neuroinflammation, which collectively drive progressive memory loss, cognitive decline, and behavioral changes. Increasing evidence implicates epigenetic dysregulation as a key contributor to these pathological processes by altering gene expression programs. Serotonergic psychedelics, which primarily act as agonists of the serotonin 2 A receptor (5-HT₂AR), have recently attracted attention for their ability to robustly promote neuroplasticity and induce sustained transcriptional changes in the brain. Preclinical studies indicate that these compounds can modulate epigenetic mechanisms, including histone modifications and DNA methylation (DNAm). This review examines the emerging intersection between psychedelic-induced epigenetic modulation and AD pathology, and proposes that targeted engagement of 5-HT₂Ars may help counteract epigenetic abnormalities that contribute to AD pathogenesis.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cites 30
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- The Current Status of Psychedelics in Psychiatry. JAMA Psychiatry February 1, 2021
- Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking Psychopharmacology July 19, 2016
- A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain Neuropsychopharmacology May 1, 2002
and 25 more in the library