Clinical Pharmacokinetics
February 14, 2017
Patrick C. Dolder, Yasmin Schmid, Andrea E. Steuer et al.
134 citations
After oral administration, lysergic acid diethylamide (LSD) reaches peak plasma concentrations of 1.3 ng/mL (100 µg dose) and 3.1 ng/mL (200 µg dose) within about 1.5 hours, with a plasma half-life of 2.6 hours. Subjective effects last 8 to 12 hours depending on dose, and peak effects occur around 2.5 to 2.8 hours after ingestion. A close relationship exists between LSD concentration and subjective response within individuals, but no correlation was found between plasma levels and effects across different people at peak concentration. The effects are related to changing plasma concentrations over time, without evidence of acute tolerance.
Drug Testing and Analysis
July 16, 2016
Andrea E. Steuer, Michael Poetzsch, Lorena Stock et al.
41 citations
A new microflow liquid chromatography tandem mass spectrometry method was developed to quantify LSD and its metabolites in human plasma, enabling detection limits of 0.01 ng/mL and separation within three minutes. In a controlled pharmacokinetic study, elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded that of LSD (median 4.2 h). However, screening for these metabolites to extend detection windows in plasma is not constructive because their concentrations are very low.
Metabolites
July 27, 2020
Andrea E. Steuer, Daria Kaelin, Martina I. Boxler et al.
32 citations
Three psychoactive stimulants—MDMA, amphetamine, and the new psychoactive substance mephedrone—alter blood metabolites in overlapping but distinct ways. Using plasma samples from controlled human administration studies and liquid chromatography-high resolution mass spectrometry, researchers identified changes in metabolites linked to energy metabolism, steroid biosynthesis, and amino acid pathways. Linoleic acid and pregnenolone-sulfate shifted similarly after intake of all three drugs. Mephedrone produced a metabolic profile more like amphetamine than MDMA, particularly in energy metabolism. These findings could guide future targeted studies on pharmacological actions and help identify biomarkers of drug use.
Journal of Proteome Research
June 27, 2018
Martina I. Boxler, Gabriel L. Streun, Matthias E. Liechti et al.
23 citations
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.
PLoS One
June 15, 2016
Andrea E. Steuer, Corina Schmidhauser, Eva H Tingelhoff et al.
18 citations
Bupropion pretreatment increased the maximum plasma concentration and overall exposure of both MDMA stereoisomers, while reducing the levels of its major metabolites by about 40%, in healthy volunteers. These changes in MDMA pharmacokinetics due to reduced CYP2D6 activity were similar to those seen in people with naturally lower CYP2D6 function (intermediate metabolizers). The alterations in stereoselectivity based on CYP2D6 activity likely have low clinical relevance. Bupropion and its metabolite levels were not affected by MDMA co-administration.
Journal of Proteome Research
July 19, 2017
Martina I. Boxler, Matthias E. Liechti, Yasmin Schmid et al.
17 citations
A single dose of MDMA (ecstasy) alters the plasma metabolome in healthy adults. In a double-blind, placebo-controlled crossover trial with 15 participants, nine metabolites showed significant concentration changes after MDMA compared with placebo. The main changes involved glycerophospholipids, which may indicate increased energy production, and the ratio of methionine-sulfoxide to methionine, a potential marker of oxidative stress. Baseline samples were essential to avoid overestimating effects due to high interday variability among individuals.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 1, 2024
Amelie Zacher, Josua Zimmermann, David M. Cole et al.
10 citations
Chronic methamphetamine users show diminished cognitive and emotional empathy toward positive stimuli, elevated punitive social behavior regardless of provocation, and heightened self-reported trait anger compared to non-users. Chronic MDMA users differ from controls only by displaying increased punitive behavior when provoked. Higher hair concentrations of both drugs may be linked to reduced cognitive empathy, and greater lifetime MDMA use correlates with more punitive behavior among MDMA users. The dopaminergic mechanism of methamphetamine may underlie social-cognitive deficits.
NeuroImage. Clinical
January 1, 2024
Antje Opitz, Josua Zimmermann, David M. Cole et al.
2 citations
Chronic users of methamphetamine and MDMA show similar deficits in conflict control and emotional processing, rather than substance-specific differences. In an emotional face-word Stroop task with anger and happy faces, both user groups exhibited smaller behavioral effects of cognitive-emotional conflict and selective impairments in processing anger, compared to amphetamine-naïve controls. These deficits were accompanied by stronger P3 event-related potential modulations, indicating altered stimulus-response mapping and decision-making. The findings suggest that chronic use of substituted amphetamines may affect noradrenergic systems, which could underlie the observed similarities. Understanding noradrenaline's role in these processes is an important direction for future research.
Translational Psychiatry
May 21, 2026
Francesco Bavato, Andrea E. Steuer, Anna M. Jacobsen et al.
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct alterations in blood levels of tryptophan-related metabolites, which may help explain their different clinical effects. In a study of 36 chronic MDMA users, 33 chronic METH users, and 71 healthy controls, METH use was linked to depleted serum tryptophan and serotonin and broad activation of kynurenine pathways, whereas MDMA use was associated with selective activation of the OH-kynurenine branch. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that persistent changes in peripheral tryptophan metabolism may contribute to the substances' contrasting addiction and psychiatric profiles.
bioRxiv Preprint Server
August 25, 2025
Francesco Bavato, Andrea E. Steuer, Anna M. Jacobsen et al.
preprint
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct changes in blood metabolites derived from tryptophan, a building block for serotonin and other signaling molecules. METH use was linked to lower serotonin levels and broad activation of the kynurenine pathway, while MDMA use was associated with a specific increase in a different branch of that pathway. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that lasting alterations in tryptophan metabolism may help explain the different clinical effects of the two drugs and could point to new therapeutic targets.