Chinese medical journal
December 20, 2023
Yingjie Du, Yunfeng Li, Xiangting Zhao et al.
71 citations
A single dose of psilocybin (2.5 mg/kg) given to mice before extinction training reduced freezing time—a measure of fear—24 hours, 6 days, and 7 days later, indicating rapid and sustained facilitation of fear extinction. Psilocybin also reversed fear-conditioning-induced decreases in hippocampal dendritic complexity, spine density, levels of BDNF and mTOR proteins, and numbers of DCX- and BrdU-positive cells (markers of neurogenesis). These findings suggest psilocybin promotes hippocampal neuroplasticity, which may partially underlie its ability to enhance fear extinction. The authors propose psilocybin could be a useful adjunct to exposure-based therapies for PTSD and other disorders involving impaired fear extinction.
Journal of Psychopharmacology
April 28, 2024
Xiangting Zhao, Yingjie Du, Yishan Yao et al.
53 citations
A single dose of psilocybin produces rapid and sustained antidepressant-like effects in both healthy mice and mice exposed to chronic corticosterone, a model of stress. Psilocybin reversed stress-induced reductions in neuroplasticity within the prefrontal cortex and hippocampus, increasing dendritic branching, spine density, and levels of synaptic proteins (p-GluA1, PSD95, synapsin-1) and activating the BDNF-mTOR signaling pathway. It also promoted neurogenesis, as indicated by more DCX-positive cells. These findings suggest that psilocybin's antidepressant action is linked to its ability to enhance structural and molecular neuroplasticity.
Frontiers in Pharmacology
February 16, 2023
Yahong Chen, Junhong Liu, Yishan Yao et al.
19 citations
Psychedelics like DOM, mescaline, and psilocin reduce mouse locomotor activity at high doses and alter rearing behavior in an inverted U-shaped pattern. Blocking the 5-HT2A receptor with M100907 reversed changes in activity, rearings, and jumps from low-dose DOM, but not holepoking. The hallucinogenic 5-HT2A agonist 25CN-NBOH produced similar effects that were diminished by M100907, while nonhallucinogenic agonists TBG and lisuride did not increase rearing. Discriminant analysis distinguished all four psychedelics from nonhallucinogenic agonists based on behavior alone, suggesting increased rearing in mice may differentiate hallucinogenic from nonhallucinogenic 5-HT2A agonists.
British journal of pharmacology
July 1, 2026
Yuanyuan Wang, Yishan Yao, Ruibin Su et al.
1 citation
The psychedelic compound 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) suppresses innate fear responses in rats by activating 5-HT₂A receptors, which recruit vasoactive intestinal polypeptide (VIP) interneurons in the prelimbic cortex. In behavioral experiments, 4-AcO-DMT reduced predator odor-evoked 22-kHz ultrasonic vocalizations, a fear-related response, through this specific cortical microcircuit mechanism. Chemogenetic activation of VIP interneurons abolished the fear-suppressing effect, confirming their role. The findings advance understanding of how serotonergic psychedelics modulate fear circuits at a neurobiological level, with potential implications for treating fear-related psychiatric disorders like phobias and anxiety.