Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways
International Journal of Molecular Sciences August 4, 2025 Masahide Arinaga, Jun Yamada, Shoichiro Maeda et al. 2 citations
Cancer-related cognitive impairment (CRCI), which includes anxiety, depression, and memory deficits, reduces quality of life but is often underrecognized. In a mouse model of Lewis lung carcinoma, tabernanthalog (TBG), a non-hallucinogenic psychedelic analog, reversed anxiety-like behavior and memory impairment. Tumor-bearing mice had reduced tryptophan levels in blood and hippocampus, downregulated serotonergic receptor genes, and upregulated pro-inflammatory cytokine genes, along with increased microglial density and activation. TBG treatment normalized microglial density and morphology and restored serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in microglial cells exposed to tumor-conditioned medium. These findings suggest TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation.