Journal of Neurochemistry
November 3, 2021
Aurora Savino, Charles D. Nichols
18 citations
Psychedelic drugs, including LSD, are being studied as potential treatments for psychiatric disorders like mood and substance use disorders. The 5-HT2A receptor is their main molecular target, and early research indicated effects on neuroplasticity genes. By analyzing RNA-sequencing data from the prefrontal cortex of rats chronically treated with LSD, the authors describe how psychedelics rewire gene co-expression networks, making them less centralized but more complex, with an overall increase in signaling entropy characteristic of highly plastic systems. This molecular-level signaling entropy mirrors the increased brain entropy observed in human neuroimaging studies, suggesting underlying mechanisms for higher-order phenomena. Network topology analysis identified potential transcriptional regulators and implicated different cell types in psychedelic activity.
bioRxiv (Cold Spring Harbor Laboratory)
June 23, 2021
Aurora Savino, Charles D. Nichols
2 citations
preprint
Psychedelic drugs are being studied as potential treatments for psychiatric conditions like mood and substance use disorders. The 5-HT2A receptor is their main molecular target, and early research indicated effects on neuroplasticity gene expression. By analyzing RNA-seq data from the prefrontal cortex of rats chronically treated with lysergic acid diethylamide (LSD), researchers found that psychedelics rewire gene co-expression networks, making them less centralized but more complex, with an overall increase in signaling entropy—a feature of highly plastic systems. This molecular signaling entropy mirrors increased brain entropy observed in human neuroimaging studies, suggesting a shared underlying mechanism. Network topology analysis also identified potential transcriptional regulators and implicated different cell types in psychedelic activity.
bioRxiv
May 29, 2026
Aurora Savino, Carla Liaci, Ilaria Bertani et al.
LSD induces gene expression patterns that oppose the transcriptional signatures of brain aging and dementia. By comparing chronic LSD treatment in rodents with age- and dementia-related gene expression changes in the human prefrontal cortex, the authors show that LSD's effects are strongly anti-correlated with these disease programs, a reversal specific compared to other pharmacological perturbations and reproducible across datasets and species. LSD also counteracts amyloid-β-induced structural and molecular alterations in primary cortical neurons, linking transcriptomic opposition to functional rescue under neurodegenerative stress. These findings suggest LSD modulates molecular and cellular pathways associated with brain aging and neurodegeneration.