Jie Zhao

2 papers in the library · 5 citations · publishing 2017-2026

Papers

Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling.

Nature January 28, 2026 Zheng Xu, Hongshuang Wang, Jingjing Yu et al. 5 citations

Psychedelics are being tested in over 200 clinical trials as potential treatments for psychiatric disorders, but how they work and their risks are not fully understood. The serotonin 2A receptor (5-HT2AR) is the main target of psychedelics. This study compared psychedelics with non-hallucinogenic analogues using cell and animal experiments, finding that 5-HT2AR signaling through a non-canonical Gi pathway is essential for hallucinogenic effects. Five cryo-electron microscopy structures of 5-HT2AR bound to these drugs were solved. A special contact between non-hallucinogenic analogues and the receptor biased signaling away from Gi. A derivative called DOI-NBOMe showed potent Gq-biased activity and therapeutic effects in mice without causing hallucinations. These findings reveal mechanisms of 5-HT2AR Gi signaling and guide the design of safer psychedelic-based drugs.

DOI: 10.1038/s41586-025-10061-7 Full text

Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats

International Journal of Molecular Sciences January 18, 2017 Qiang Wang, Qinghui Wu, Junpeng Wang et al.

Long-term methoxetamine, a ketamine analog used recreationally, causes bladder dysfunction and inflammation in rats. Female rats injected daily with 30 mg/kg methoxetamine or ketamine for 4 or 12 weeks showed increased urination frequency, damaged bladder lining, inflammatory cell infiltration, and fibrosis. Treated rats had elevated levels of pro-inflammatory cytokines and markers of fibrosis. Methoxetamine also directly damaged human urothelial cells and increased inflammatory signals. The findings suggest methoxetamine's bladder effects resemble ketamine-induced cystitis.

DOI: 10.3390/ijms18010117