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 via OpenAlex
Summary
A single 125 mg dose of MDMA alters dozens of endogenous metabolites in human plasma, including increases in cortisol, pregnenolone sulfate, and several inflammation mediators, alongside a decrease in calcitriol. These changes suggest heightened stress and serotonergic activity, activation of inflammatory pathways, and potential reduction in neuroprotective factors for brain dopamine neurons.
Study at a glance
| Characteristics | Placebo-controlled crossover study Peer reviewed |
|---|---|
| Population | Human participants |
| Intervention | MDMA |
| Dose | 125 mg |
| Topics | MDMA Serotonin |
| Keywords | Metabolome Pharmacology Metabolomics Metabolite |
| Citations | 23 |
| Key finding | 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.