bioRxiv (Cold Spring Harbor Laboratory)
September 26, 2023
Yi-Ting Chiu, Wei Wang, Pierre Llorach et al.
15 citations
preprint
Psychedelic drugs such as LSD and psilocybin show promise as treatments for depression, anxiety, PTSD, migraine, and cluster headaches by activating the 5-HT2A receptor (HTR2A). Researchers engineered several new mouse lines to study the role of HTR2A and the neurons that express it. One line allows visualization of the receptor and identification of HTR2A-containing cells, providing a detailed anatomical map. Another line has a humanized version of the receptor, and a third enables targeted genetic manipulation. The mice exhibited expected behavioral responses to psychedelics, confirming their usefulness. Electrophysiology showed that serotonin increases firing of specific pyramidal neurons through HTR2A, consistent with the receptor's location on the cell surface. These tools will help clarify how psychedelics work at molecular, cellular, and behavioral levels.
bioRxiv (Cold Spring Harbor Laboratory)
November 15, 2022
Gavin P. Schmitz, Yi-Ting Chiu, Gabriele M. König et al.
15 citations
preprint
Psilocin, the active compound in psilocybin mushrooms, activates serotonin 2A receptors (5-HT2ARs) in the prefrontal cortex (PFC), but its specific effects on PFC neurons were unclear. Using slice electrophysiology in mice, researchers found that psilocin application onto layer 5 pyramidal neurons in the prelimbic PFC produced variable firing changes (increase, decrease, or no change) in unspecific neurons. However, in neurons identified as expressing 5-HT2ARs, psilocin consistently increased firing without altering synaptic transmission. The results demonstrate that psilocin evokes strong, 5-HT2AR- and Gαq-dependent firing changes in the PFC, offering insights into how psychedelics affect a brain region key to their therapeutic actions.
Translational Psychiatry
October 6, 2025
Gavin P. Schmitz, Yi-Ting Chiu, Mia L. Foglesong et al.
13 citations
Psilocybin's active metabolite psilocin increases activity in the medial prefrontal cortex (mPFC), a brain region rich in 5-HT2A receptors. A specific population of neurons in the prelimbic/anterior cingulate mPFC that express these receptors becomes more excitable and fires more in response to psilocin and a selective 5-HT2A receptor compound, effects dependent on both the receptor and Gα q signaling. A novel non-hallucinogenic psychedelic compound produced similar effects. These results point to membrane-bound 5-HT2A receptors and intracellular Gα q signaling as potential therapeutic targets for psychedelic-associated plasticity.
Journal of Neuroscience
November 10, 2025
Sarah N. Magee, Allison C. Sereno, Maria Echeveste-Sanchez et al.
Psilocin, the active metabolite of psilocybin, acutely reduced voluntary ethanol consumption in mice exposed to two models of chronic ethanol exposure without altering locomotor behavior. It increased activation of the central amygdala (CeA) and decreased relative activation of corticotropin-releasing factor type 1 (CRF1) receptors in CeA subregions of ethanol-naive female mice, with similar effects observed in chronic ethanol-exposed mice at 24 and 72 hours of withdrawal. Psilocin also elevated corticosterone levels at 24 hours but not at 72 hours of withdrawal. These findings indicate that psilocin engages CeA circuitry and reduces relative CRF1 activation alongside acute reductions in drinking, helping explain potential therapeutic mechanisms for alcohol use disorder.