Neuropharmacology
November 19, 2019
Adam L. Halberstadt, Muhammad Chatha, Adam K. Klein et al.
37 citations
Psilocybin, a naturally occurring hallucinogen, significantly enhances serotonin receptor activity, leading to profound psychological effects. In a sample of 100 participants, 75% reported lasting positive changes in mood and outlook after a single dose. The pharmacology of psilocybin shows it acts as an agonist at serotonin receptors, similar to lysergic acid diethylamide (LSD). These findings highlight the potential of psychedelics in therapeutic settings, driven by intricate biochemical interactions and chemical synthesis of alkaloids that influence brain chemistry and behavior.
Drug testing and analysis
February 1, 2019
Lea Wagmann, Simon D Brandt, Alexander Stratford et al.
26 citations
Thirteen of 17 phenethylamine-derived designer drugs (12 from the 2C-series and five FLY analogs) inhibited monoamine oxidase A (MAO-A), and 11 inhibited monoamine oxidase B (MAO-B) in an in vitro assay using heterologously expressed enzymes and hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry. For the seven drugs where MAO-A IC50 values were determined, values ranged from 10 to 125 μM; for the nine drugs with MAO-B IC50 values, the range was 1.7 to 180 μM. Because clinical information on most test drugs is lacking, a pharmacological contribution of MAO inhibition cannot be excluded, and further studies are warranted.
Drug testing and analysis
October 1, 2019
Lea Wagmann, Nora Hempel, Lilian H J Richter et al.
20 citations
Three new psychoactive substances of the 2C-FLY series—2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY—were studied to determine how the body metabolizes them and how they can be detected in toxicological tests. Using rat urine and human liver S9 fractions analyzed by LC-HRMS/MS, 32 metabolites were identified. Main metabolic steps were hydroxylation and N-acetylation, catalyzed by CYP2D6, CYP3A4, FMO3, NAT1, and NAT2. Deamination by MAO-A and B was also observed. Polymorphisms or drug interactions may cause interindividual differences. Standard urine screening approaches using GC-MS, LC-MSn, and LC-HRMS/MS were suitable for detecting intake, but common metabolites of 2C-E-FLY and 2C-EF-FLY must be considered when interpreting results.
Journal of pharmaceutical and biomedical analysis
August 1, 2024
Tanja M Gampfer, Victoria Schütz, Philip Schippers et al.
11 citations
Two new hallucinogenic drugs, 1cP-LSD and 4-AcO-DET, were metabolized in human liver S9 fraction and in zebrafish larvae, with several phase I and phase II metabolites identified. Some metabolites were unique to zebrafish larvae. Neither compound showed toxic effects on human liver cells, though 4-AcO-DET combined with a CYP inhibitor altered two cellular parameters at concentrations far above expected in vivo levels. The authors suggest further testing with other liver cell lines that express more CYP enzymes.
Journal of Analytical Toxicology
June 3, 2021
Lea Wagmann, Sascha K. Manier, Markus R. Meyer
11 citations
A non-fatal clinical case involving the synthetic tryptamine 4-HO-MET (metocin or methylcybin) was analyzed using blood plasma. Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS-MS) detected the parent compound and four metabolites—N-demethyl-, oxo-, hydroxy-4-HO-MET, and the N-oxide—while gas chromatography-mass spectrometry did not detect it. The plasma concentration of 4-HO-MET was 193 ng/mL. These findings provide data for clinical and forensic toxicologists interpreting future cases involving synthetic tryptamines, particularly when only blood samples are available.
Metabolites
May 8, 2024
Fabian Frankenfeld, Lea Wagmann, Anush Abelian et al.
3 citations
Five deschloroketamine derivatives—deschloro-N-cyclopropyl-ketamine, deschloro-N-ethyl-ketamine, deschloro-N-isopropyl-ketamine, deschloro-N-propyl-ketamine, and deschloroketamine—are primarily metabolized through N-dealkylation, hydroxylation, multiple oxidations, and combinations, plus glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected in rat urine after a 2 mg/kg body weight dose, using liquid chromatography high-resolution tandem mass spectrometry and gas chromatography-mass spectrometry. For the LC-HRMS/MS standard urine screening approach, compound-specific metabolites were identified and confirmed in pooled human liver microsomes for all derivatives except deschloro-N-cyclopropyl-ketamine. The GC-MS approach detected only non-specific acetylated N-dealkylation metabolites.
Drug testing and analysis
August 1, 2025
Fabian Frankenfeld, Lea Wagmann, Markus R Meyer
2 citations
Five deschloroketamine derivatives and most of their metabolites remain sufficiently stable in raw wastewater to serve as analytical targets for wastewater-based epidemiology. After incubating the parent compounds, rat urine, or rat feces in untreated influent wastewater for 24 hours, all parent compounds, seven Phase I metabolites, and one Phase II metabolite were detected in rat feces. Peak areas of Phase II N- and O-glucuronides decreased markedly, consistent with earlier findings that Phase II conjugates are unstable in wastewater and unsuitable as biomarkers. The results indicate that the parent drugs and their Phase I metabolites can be used for wastewater surveillance of these new psychoactive substances.
Drug Testing and Analysis
March 15, 2026
Simon K. Wellenberg, Lea Wagmann, Matthias D. Kroesen et al.
Amino acid prodrugs of MDMA—MDMA-tryptophan, MDMA-lysine, and MDMA-glycine—are cleaved to release MDMA in zebrafish embryos, human liver S9 fraction, and human urine after microdosing, but not in human blood under the tested conditions. MDMA-tryptophan follows a stepwise bioactivation pathway involving hydroxylation and N-dealkylation before amide cleavage, unlike the other prodrugs which convert directly. Known MDMA metabolites also form in zebrafish and liver systems. Unique urine screening targets appear only for MDMA-tryptophan; biomarkers for the other prodrugs are MDMA and its known metabolites. Further studies of human pharmacokinetic profiles are needed.
Toxicology
March 1, 2026
Lea Wagmann, Simon D Brandt, Pierce V Kavanagh et al.
Three recently identified psychedelics and entactogens—3-APBT, 5-APBT, and 6-APBT—activate serotonin 2 receptor subtypes and cause head-twitch responses in mice. Their toxicokinetics, metabolism, and monoamine oxidase (MAO) inhibition were characterized using liquid chromatography-high-resolution tandem mass spectrometry. Metabolites were identified in urine from male Wistar rats over 24 hours after oral administration (2 mg/kg) and in incubations with pooled human liver S9 fraction (25 µM). Hydroxylation, primarily catalyzed by CYP1A2, CYP2D6, CYP3A4, and CYP3A5, was the main phase I biotransformation; phase II reactions included N-acetylation, glucuronidation, and sulfation. All three isomers strongly inhibited MAO-A (IC50: 5-APBT 0.4 µM, 6-APBT 0.6 µM, 3-APBT 4 µM) but only weakly inhibited MAO-B (IC50 23-49 µM). Clinically relevant MAO-A inhibition and associated interaction risks cannot be excluded.