PMID- 29947220 OWN - NLM STAT- MEDLINE DCOM- 20190826 LR - 20190826 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 17 IP - 8 DP - 2018 Aug 3 TI - Human Metabolome Changes after a Single Dose of 3,4-Methylenedioxymethamphetamine (MDMA) with Special Focus on Steroid Metabolism and Inflammation Processes. PG - 2900-2907 LID - 10.1021/acs.jproteome.8b00438 [doi] AB - The intake of 3,4-methylenedioxymethamphetamine (MDMA) is known to increase several endogenous substances involved in steroid and inflammation pathways. Untargeted metabolomics screening approaches can determine biochemical changes after drug exposure and can reveal new pathways, which might be involved in the pharmacology and toxicology of a drug of abuse. We analyzed plasma samples from a placebo-controlled crossover study of a single intake of MDMA. Plasma samples from a time point before and three time points after the intake of a single dose of 125 mg MDMA were screened for changes of endogenous metabolites. An untargeted metabolomics approach on a high-resolution quadrupole time-of-flight mass spectrometer coupled to liquid chromatography with two different chromatographic systems (reversed-phase and hydrophobic interaction liquid chromatography) was applied. Over 10 000 features of the human metabolome were detected. Hence, 28 metabolites were identified, which showed significant changes after administration of MDMA compared with placebo. The analysis revealed an upregulation of cortisol and pregnenolone sulfate 4 h after MDMA intake, suggesting increased stress and serotonergic activity. Furthermore, calcitriol levels were decreased after the intake of MDMA. Calcitriol is involved in the upregulation of trophic factors, which have protective effects on brain dopamine neurons. The inflammation mediators hydroxyeicosatetraenoic acid, dihydroxyeicosatetraenoic acid, and octadecadienoic acid were found to be upregulated after the intake of MDMA compared with placebo, which suggested a stimulation of inflammation pathways. FAU - Boxler, Martina I AU - Boxler MI AD - Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine , University of Zurich , 8057 Zurich , Switzerland. FAU - Streun, Gabriel L AU - Streun GL AD - Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine , University of Zurich , 8057 Zurich , Switzerland. FAU - Liechti, Matthias E AU - Liechti ME AD - Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, Department of Clinical Research , University Hospital Basel, University of Basel , 4031 Basel , Switzerland. FAU - Schmid, Yasmin AU - Schmid Y AD - Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, Department of Clinical Research , University Hospital Basel, University of Basel , 4031 Basel , Switzerland. FAU - Kraemer, Thomas AU - Kraemer T AUID- ORCID: 0000-0002-3283-606X AD - Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine , University of Zurich , 8057 Zurich , Switzerland. FAU - Steuer, Andrea E AU - Steuer AE AUID- ORCID: 0000-0001-8983-2353 AD - Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine , University of Zurich , 8057 Zurich , Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180713 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (Inflammation Mediators) RN - 0 (Steroids) RN - 73R90F7MQ8 (Pregnenolone) RN - FXC9231JVH (Calcitriol) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - WI4X0X7BPJ (Hydrocortisone) MH - Blood Specimen Collection MH - Calcitriol/metabolism MH - Cross-Over Studies MH - Humans MH - Hydrocortisone/metabolism MH - Inflammation/*chemically induced MH - Inflammation Mediators/metabolism MH - Mass Spectrometry MH - Metabolome/*drug effects MH - Metabolomics/methods MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Pregnenolone/metabolism MH - Steroids/*metabolism MH - Time Factors OTO - NOTNLM OT - 3,4-methylenedioxymethamphetamine (MDMA) OT - calcitriol OT - ecstasy OT - inflammation OT - placebo-controlled OT - pregnenolone sulfate OT - untargeted metabolomics EDAT- 2018/06/28 06:00 MHDA- 2019/08/27 06:00 CRDT- 2018/06/28 06:00 PHST- 2018/06/28 06:00 [pubmed] PHST- 2019/08/27 06:00 [medline] PHST- 2018/06/28 06:00 [entrez] AID - 10.1021/acs.jproteome.8b00438 [doi] PST - ppublish SO - J Proteome Res. 2018 Aug 3;17(8):2900-2907. doi: 10.1021/acs.jproteome.8b00438. Epub 2018 Jul 13.