Journal of the American Chemical Society
April 10, 2024
Wei-Li Lee, Xavier Westergaard, Christopher Hwu et al.
18 citations
A novel small molecule fluorescent agent called SERTlight specifically labels serotonin neurons in the mammalian brain. SERTlight is a substrate for the serotonin transporter (SERT) and accumulates inside serotonin neurons, producing a bright and selective optical signal. Unlike many other agents, SERTlight does not activate serotonin receptors or other common targets and is not released by neuronal activity or drugs like MDMA. It is compatible with other imaging tools and can label distant axonal projections while allowing simultaneous measurement of serotonin release. This new tool enables detailed study of the serotonin system in health and disease.
bioRxiv Preprint Server
March 4, 2024
Umed Boltaev, Hyun W. Park, Keaon R. Brown et al.
4 citations
preprint
Classic psychedelics are thought to work by inducing neuroplasticity, often measured as dendritic arbor growth. This study tested whether psychedelics directly activate the TrkB receptor or BDNF/TrkB signaling, and whether they cause morphological growth in primary cortical neurons. Using a multimodal screening platform, the authors found that psychedelics do not directly modulate TrkB or BDNF-TrkB signaling, and that 5-HT2A receptor expression and functional levels are low. Psychedelics did not induce dendritogenesis, unlike BDNF which did. These results challenge previous findings and highlight the need for rigorous methods in studying neuroplasticity.
Journal of Psychopharmacology
October 4, 2025
Michael G. Palfreyman, Geoffrey B. Varty, Erik M. Stang et al.
3 citations
Classic psychedelic tryptamines show promise for neuropsychiatric disorders, but their broad utility is limited by properties requiring complex delivery and the enigmatic role of the 'psychedelic experience' in therapeutic efficacy. Reducing their mechanism to mere 5-HT2A receptor activation raises the question of whether efficacy is achievable without psychedelic effects. These molecules also interact with other serotonin receptors (e.g., 5-HT1A, 5-HT2C) and non-serotonergic receptors, necessitating further scrutiny of their polypharmacology. This perspective reviews limitations of current non-conjugated tryptamines, explores approaches to improve them, and discusses developing next-generation psychedelic and non-psychedelic compounds, along with the pharmacology underlying these potential therapies.