ArticleFrontiers in pharmacology2025
Integrated metabolomics and gut microbiota analysis to explore the potential mechanism of levo-tetrahydropalmatine against ketamine addiction.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Metabolic and gut microbiota (GM) disturbance play a significant role in the complex pathogenesis of substance dependence. Although levo-tetrahydropalmatine (l-THP) demonstrates therapeutic potential in drug addiction, the underlying mechanism remains elusive. Methods: The efficacy of l-THP was assessed using a conditioned place preference (CPP) paradigm. In this research, we combined metabolomics with gut microbiota analysis to investigate the potential mechanisms underlying l-THP's intervention in ketamine (KET) addiction. Results: L-THP effectively relieved hippocampus (Hip) pathological changes and attenuated KET-induced rewarding effects. Metabolomic profiling of serum and urine samples revealed a total of 194 distinct metabolites, including 3-methoxytyramine, 3-hydroxyphenylacetic acid, and phosphorylcholine, involving glycerophospholipid metabolism, tyrosine metabolism, phenylalanine metabolism, dopaminergic synapse, teichoic acid biosynthesis, staurosporine biosynthesis, and lysine biosynthesis metabolism pathways. L-THP also enriched 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.
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