Molecular Psychiatry
May 7, 2021
Wei Yan, Lijia Chang, Kenji Hashimoto
242 citations
The antidepressant effects of the drug (R,S)-ketamine, a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), are not primarily due to blocking the N-methyl-D-aspartate receptor (NMDAR), despite initial assumptions. Preclinical studies in rodents show arketamine has more potent and longer-lasting antidepressant-like effects than esketamine, even though arketamine binds less strongly to NMDAR. Clinical trials with other NMDAR-blocking compounds failed to produce robust antidepressant effects in humans, indicating rodent findings do not always translate. The exact molecular mechanisms remain unclear. This review covers recent findings on these mechanisms, the possible roles of the brain-gut-microbiota and brain-spleen axes, and arketamine's potential for treating cognitive impairment, Parkinson's disease, osteoporosis, inflammatory bowel diseases, and stroke.
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.
Journal of Positive Psychology
February 6, 2025
Yuling Wang, Tonglin Jiang, Wei Yan
Awe, an emotion that makes people feel part of something larger than themselves, appears to promote wise reasoning—the ability to consider different perspectives, seek compromise, and recognize the limits of one's own knowledge. Across four studies involving 3,700 participants, including cross-sectional, longitudinal, and experimental designs, awe consistently predicted or enhanced wise reasoning. This effect was not simply due to awe being a positive emotion, nor to feeling small. Instead, the relationship was explained by a sense of self-transcendence, or feeling connected to something beyond the self. The findings suggest that experiencing awe can help people reason more wisely, especially in conflicts.
Journal of Affective Disorders
February 1, 2022
Jianyu Que, Le Shi, Wei Yan et al.
Among 16,220 hospital workers in Wuhan, China, surveyed during the COVID-19 pandemic, 13.3% reported suicidal ideation in the past month. Exposure to COVID-19-related traumatic events was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling for potential confounders, nightmares—but not insomnia, depression, or anxiety—were independent risk factors for suicidal ideation. Pathway analyses indicated that the relationship between traumatic event exposure and suicidal ideation was fully mediated by nightmares, with a proportion mediated of 66.4%. The authors suggest that nightmare intervention might be considered a component of suicide prevention strategies.