ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1698866
This article is part of the Research TopicNovel Pharmacological Interventions in Emotional and Neuropsychiatric DisordersView all 7 articles
Integerated metabolomics and gut microbiota analysis to explore protential mechanism of levo-tetrahydropalmatine against ketamine addiction
Provisionally accepted
- 1School of Pharmacy, Shanxi Medical University, Taiyuan, China
- 2China Institute of Radiation Protection, Taiyuan, China
- 3Shanxi Medical University School of Forensic Medicine, Jinzhong, China
- 4Department of Pharmacy, Shanxi Province Cancer Hospital, Taiyuan, China
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Introduction: Metabolic and gut microbiota disturbance play a significant role in the complex pathogenesis of substance dependence. Although levo-tetrahydropalmatine (l-THP) demonstrates therapeutic potential in drug addiction, but the underlying mechanism remains elusive. Methods: The efficacy of l-THP was assessed using a conditioned place preference (CPP) paradigm. This research combined metabolomics with gut microbiota analysis to investigate the potential mechanisms underlying l-THP's intervention in KET addiction. Results: L-THP effectively relieved Hippocampus (Hip) pathological changes and attenuated KET induced rewarding effect. Metabolomic profiling of serum and urine samples revealed a total of 194 distinct metabolites, such as 3-Methoxytyramine, 3-Hydroxyphenylacetic acid, phosphorylcholine, involving glycerophospholipid metabolism, tyrosine metabolism, phenylalanine metabolism, dopaminergic synapse, teichoic acid biosynthesis, staurosporine biosynthesis, and lysine biosynthesis metabolism pathways. L-THP also enriched Firmicutes, Lactobacillus, Dubosiella, unclassied_Clostridia_UCG_014, and Ligilactobacillus. While l-THP decreased the level of Bacteroidota, Campylobacterota, Patescibacteria, unclassified_Bacilli, UCG_005, Prevotella and Romboutsia. Moreover, Spearman's correlation analysis showed that discriminative metabolites were closely correlated with special bacteria. Conclusion: The findings demonstrated that l-THP might serve as a promising intervention strategy for KET addiction by regulating serum and urine metabolism and gut microbiota.
Keywords: L-Tetrahydropalmatine, Ketamine addiction, Metabolomics, Gut Microbiota, Correlation analysis
Received: 04 Sep 2025; Accepted: 08 Oct 2025.
Copyright: © 2025 Du, Ma, Gao, Su, Yun and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yan Du, ydu@sxmu.edu.cn
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