Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways
Masahide Arinaga, Jun Yamada, Shoichiro Maeda, A Okamura, Yuji Oshima, Liye Zhang, Yiying Han, Kyoko Iinuma, Shozo Jinno
International Journal of Molecular Sciences August 4, 2025 Peer reviewed DOI: 10.3390/ijms26157519 via OpenAlex
Summary
Tabernanthalog (TBG), a non-hallucinogenic psychedelic analog, shows promise in alleviating cancer-related cognitive impairment (CRCI) in a mouse model. Mice with Lewis lung carcinoma exhibited increased anxiety and memory deficits alongside reduced tryptophan and altered serotonergic gene expression. TBG treatment improved these symptoms by normalizing microglial density and restoring gene expression related to serotonin and inflammation. The findings indicate TBG's potential as a therapeutic option for enhancing cognitive and emotional health in cancer patients.
Study at a glance
| Population | Lewis lung carcinoma (3LL) mouse model |
|---|---|
| Key finding | TBG treatment reversed anxiety-like behavior and memory impairment in tumor-bearing mice, suggesting its potential to alleviate CRCI symptoms. |
Abstract
Cancer-related cognitive impairment (CRCI)-encompassing anxiety, depression, and memory deficits-significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer.