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 M Iinuma, Shozo Jinno
International Journal of Molecular Sciences August 4, 2025 DOI: 10.3390/ijms26157519 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Lewis lung carcinoma (3LL) mouse model |
| Intervention | Tabernanthalog (TBG) |
| Topics | Serotonin |
| Keywords | Neuroinflammation Hippocampal formation Pharmacology Receptor |
| Citations | 2 |
| Key points | Tabernanthalog (TBG) reversed anxiety-like behavior and memory impairment in tumor-bearing mice by normalizing microglial activation and restoring serotonergic receptor and cytokine gene expression. |
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.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 16
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Experimental Brain Research June 1, 2013
- Human brain effects of DMT assessed via EEG-fMRI. Proceedings of the National Academy of Sciences March 28, 2023
and 11 more in the library