Comparative Untargeted Metabolomics Analysis of the Psychostimulants 3,4-Methylenedioxy-Methamphetamine (MDMA), Amphetamine, and the Novel Psychoactive Substance Mephedrone after Controlled Drug Administration to Humans.

Andrea E Steuer,Vincenzo Abbate,Friederike Holze,Paul I Dargan,Daria Kaelin,Martina I Boxler,Matthias E Liechti,Patrick Vizeli,Thomas Kraemer,Joanna Czerwinska,Lisa Eisenbeiss

doi:10.3390/metabo10080306

Abstract

Psychoactive stimulants are a popular drug class which are used recreationally. Over the last decade, large numbers of new psychoactive substances (NPS) have entered the drug market and these pose a worldwide problem to human health. Metabolomics approaches are useful tools for simultaneous detection of endogenous metabolites affected by drug use. They allow identification of pathways or characteristic metabolites, which might support the understanding of pharmacological actions or act as indirect biomarkers of consumption behavior or analytical detectability. Herein, we performed a comparative metabolic profiling of three psychoactive stimulant drugs 3,4-methylenedioxymethamphetamine (MDMA), amphetamine and the NPS mephedrone by liquid chromatography-high resolution mass spectrometry (LC-HRMS) in order to identify common pathways or compounds. Plasma samples were obtained from controlled administration studies to humans. Various metabolites were identified as increased or decreased based on drug intake, mainly belonging to energy metabolism, steroid biosynthesis and amino acids. Linoleic acid and pregnenolone-sulfate changed similarly in response to intake of all drugs. Overall, mephedrone produced a profile more similar to that of amphetamine than MDMA in terms of affected energy metabolism. These data can provide the basis for further in-depth targeted metabolome studies on pharmacological actions and search for biomarkers of drug use.

Highlights

Drugs of abuse (DOA) consumption remains a worldwide threat to human health, withDrugs of abuse (DOA) consumption remains a worldwide threat to human health, large numbers of new psychoactive substances (NPS) emerging each year
The aim of the present study was to apply untargeted metabolomics profiling on plasma samples from controlled drug administration studies to humans to investigate (a) the changes in the human metabolome caused by the psychostimulants amphetamine and mephedrone, (b) to compare the influence of the psychostimulants drugs (MDMA [24], amphetamine and mephedrone) on the human metabolome, and (c) to identify biological pathways affected by the intake of psychostimulants which would be valuable for further targeted analysis
The plasma samples selected for the presented comparative, metabolic profiling study with the three psychostimulant drugs MDMA, amphetamine and mephedrone were obtained from former clinical studies initially designed for investigations of pharmacological effects [5,30] and pharmacokinetic parameters

Summary

Introduction

Drugs of abuse (DOA) consumption remains a worldwide threat to human health, with. Drugs of abuse (DOA) consumption remains a worldwide threat to human health, large numbers of new psychoactive substances (NPS) emerging each year. By the end of 2018, more than with large numbers of new psychoactive substances (NPS) emerging each year. By the end of 2018, 700 NPS were being monitored by the European Monitoring Centre for Drugs and Drug Addiction more than 700 NPS were being monitored by the European Monitoring Centre for Drugs and Drug (EMCDDA), with 55 newly reported in 2018. About one third of the NPS reported in Europe belong to the Addiction (EMCDDA), with 55 newly reported in 2018. About one third of the NPS reported in class of psychostimulants [1].ofPsychoactive stimulants are a popular of drugs which are Europe belong to the class psychostimulants [1].

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