Alterations in tryptophan and purine metabolism in cocaine addiction: A metabolomic study

Abstract

Background: Mapping metabolic "signatures" can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets. Objective: We examined the differences in metabolites related to the tyrosine, tryptophan, purine, and oxidative stress pathways between cocaine-dependent subjects and healthy controls. Several of these metabolites serve as biological indices underlying the mechanisms of reinforcement, toxicity, and oxidative stress. Methods: Metabolomic analysis was performed in 18 DSM-IV-diagnosed cocaine-dependent individuals with at least 2 weeks of abstinence and ten drug-free controls. Plasma concentrations of 37 known metabolites were analyzed and compared using a liquid chromatography electrochemical array platform. Multivariate analyses were used to study the relationship between severity of drug use [Addiction Severity Index (ASI) scores] and biological measures. Results: Cocaine subjects showed significantly higher levels of n-methylserotonin (p< 0.0017) and guanine (p