Serotonergic psychedelics as epigenetic modulators: A paradigm shift in Alzheimer's disease therapeutics.
Neuroscience and biobehavioral reviews May 1, 2026 Esmaeel G Gojani, Houman Farzin, Robert J Sutherland et al.
Alzheimer's disease involves amyloid-β accumulation, tau pathology, synaptic dysfunction, and neuroinflammation, driving progressive memory loss and cognitive decline. Epigenetic dysregulation is increasingly recognized as contributing to these processes by altering gene expression. Serotonergic psychedelics, acting as agonists of the serotonin 2A receptor, promote neuroplasticity and induce sustained transcriptional changes in the brain. Preclinical studies suggest these compounds can modulate epigenetic mechanisms, including histone modifications and DNA methylation. This review proposes that targeted engagement of 5-HT2A receptors may help counteract epigenetic abnormalities that contribute to Alzheimer's disease pathogenesis.