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.
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.