Human Metabolome Changes after a Single Dose of 3,4-Methylenedioxymethamphetamine (MDMA) with Special Focus on Steroid Metabolism and Inflammation Processes
Martina I. Boxler, Gabriel L. Streun, Matthias E. Liechti, Yasmin Schmid, Thomas Kræmer, Andrea E. Steuer
Journal of Proteome Research June 27, 2018 DOI: 10.1021/acs.jproteome.8b00438 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled crossover study Peer reviewed |
|---|---|
| Population | Human participants |
| Intervention | MDMA |
| Dose | 125 mg |
| Topics | MDMA Serotonin |
| Keywords | Metabolome Pharmacology Metabolomics Metabolite Downregulation and upregulation Drug detection Inflammation Homovanillic acid Endocrinology Biochemistry Chromatography |
| Citations | 23 |
| Key points | MDMA intake upregulates cortisol, pregnenolone sulfate, and inflammation mediators (hydroxyeicosatetraenoic acid, dihydroxyeicosatetraenoic acid, octadecadienoic acid) while downregulating calcitriol. |
Abstract
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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 10
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- 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 Metabolites July 27, 2020
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings Neural Regeneration Research February 22, 2024
and 5 more in the library
Cites 15
- Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study PLoS One May 4, 2012
- The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans Clinical Pharmacology & Therapeutics June 15, 2011
- A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers Journal of Psychopharmacology March 1, 2006
- Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination The International Journal of Neuropsychopharmacology October 8, 2013
- Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans Psychoneuroendocrinology April 19, 2014
and 10 more in the library