Journal of Analytical Toxicology
March 4, 2015
Nathalie A. Desrosiers, Johannes G. Ramaekers, Émeline Chauchard et al.
136 citations
THC, the main psychoactive compound in cannabis, impairs psychomotor performance, cognition, and driving ability. Occasional cannabis smokers showed significantly more difficulty compensating for tracking error and greater decline in divided attention performance than frequent smokers after smoking one 6.8% THC cigarette. No differences between groups were found on working memory or risk-taking tasks. The results suggest that frequent users develop some tolerance to psychomotor impairment, with implications for driving under the influence cases.
Therapeutic Drug Monitoring
May 21, 2008
Erin A Kolbrich, Robert S. Goodwin, David A. Gorelick et al.
127 citations
After a low oral dose of MDMA (1.0 mg/kg), average maximum plasma concentrations were 162.9 ng/mL for MDMA and 171.9 ng/mL for its metabolite HMMA. After a high dose (1.6 mg/kg), MDMA's average maximum concentration rose significantly to 291.8 ng/mL, while HMMA's remained unchanged at 173.5 ng/mL, indicating nonlinear pharmacokinetics. The half-lives of MDMA, MDA, and HMMA ranged from roughly 7 to 13.5 hours. This study provides the first MDMA plasma pharmacokinetic data from Black participants and female participants, with more frequent and extended sampling than prior work.
Journal of Analytical Toxicology
April 20, 2022
Amanda L A Mohr, Barry K. Logan, Melissa F. Fogarty et al.
66 citations
A critical review of published case reports from January 2017 through December 2020 identified 1,319 cases of adverse events associated with novel psychoactive substances (NPS), including 378 overdose fatalities, 771 cases requiring clinical treatment or hospitalization, and 170 cases of driving under the influence. The review covers chemistry, pharmacology, user profiles, and clinical symptoms for over 60 NPS, with 50 substances reported for the first time compared to the previous four years. Cases span synthetic cannabinoids, NPS stimulants, hallucinogens, benzodiazepines, and opioids. The findings aim to improve awareness and characterization of emerging international drug threats.
Journal of Analytical Toxicology
October 1, 2009
T. T. Abraham, Allan J. Barnes, Richie H. Lowe et al.
56 citations
After a single oral dose of MDMA (ecstasy), the drug and its metabolites are excreted in urine over an extended period, with the metabolite HMMA detectable longer than MDMA itself. In a double-blind study, healthy adult MDMA users received placebo, 1.0 mg/kg, or 1.6 mg/kg doses. From 916 urine specimens provided by 16 participants, median peak concentrations after the higher dose were 21,470 ng/mL for MDMA and 20,793 ng/mL for HMMA, with HMMA's last detection exceeding MDMA's by over 33 hours. In the first 24 hours, 30.2-34.3% of total urinary excretion occurred. Including HMMA in urine testing improves detection of MDMA exposure but requires hydrolysis of the sample.
International Journal of Molecular Sciences
December 4, 2020
Sara Malaca, Alfredo Fabrizio Lo Faro, Alice Tamborra et al.
48 citations
Tryptamines are 5-HT2A receptor agonists that alter perceptions of reality. Their prevalence in drug overdoses is low but increasing, yet they are not part of typical toxicology testing, so their contribution may be underestimated. From 2015 to 2020, 22 new analytical methods, primarily liquid chromatography tandem mass spectrometry, were developed to identify tryptamines and metabolites in biological samples. The most prevalent tryptamines are 5-MeO-DiPT, 5-MeO-DALT, and DMT. Morbidity from tryptamine intake is considerable, and clinicians and laboratorians need updated data on this public health threat.
Clinical Chemistry
June 30, 2017
Marilyn A. Huestis, Simon D. Brandt, Suman Rana et al.
42 citations
Novel psychoactive substances (NPS) have been present in clinical and forensic toxicology for over a century, with early examples including heroin, LSD, MDMA, and GHB. After synthetic cannabinoids emerged in the early 2000s, hundreds of synthetic cathinones, benzodiazepines, and opioids rapidly appeared. Toxicology laboratories, once focused on a narrow range of compounds, now face potent fentanyl derivatives mixed with or substituted for heroin, causing rising fatalities. Labs struggle to detect short-lived drug analogs, unknown urinary metabolites, and lack reference standards. Four international experts discuss what drove the global NPS market, how toxicology laboratories can address these challenges, and how public health and law enforcement can reduce NPS-related morbidity and mortality.
Clinical Chemistry
January 23, 2009
Allan J. Barnes, Bruno Spinosa de Martinis, David A. Gorelick et al.
38 citations
In a controlled study, 15 healthy volunteers with prior MDMA use received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral doses of MDMA in random order while wearing sweat patches for up to 7 days. MDMA was the main substance found in 59.7% of patches, with concentrations up to 3007 ng/patch; its metabolite MDA appeared in 29.4% of patches at lower levels, while other metabolites were undetected. At the 25-ng/patch threshold, 35% of patches were positive for MDMA. Sweat testing reliably detects MDMA use, but high variability in excretion means results should be interpreted qualitatively, not quantitatively.
Clinical Chemistry
December 19, 2007
Erin A Kolbrich, Ross H. Lowe, Marilyn A. Huestis
36 citations
A two-dimensional gas chromatography–mass spectrometry method with cryofocusing simultaneously quantifies MDMA, its metabolites MDA, HMMA, and HMA, and MDEA in human plasma. Limits of quantification were 1.0 μg/L for MDA and 2.5 μg/L for the other four compounds. Calibration curves were linear up to 100 μg/L for MDA and HMA and up to 400 μg/L for MDEA, MDMA, and HMMA, with correlation coefficients above 0.997. Extraction efficiencies from plasma were at least 85%, recoveries ranged from 85.6% to 107.2% of target, and intra- and interassay imprecision was below 8.5% at three concentrations. None of 66 tested exogenous compounds interfered. The assay achieves low quantification limits suitable for pharmacokinetic studies and may apply to other analytes and complex matrices.
Clinical Chemistry
October 7, 2011
Andrea E. Schwaninger, Markus R. Meyer, Allan J. Barnes et al.
33 citations
After oral MDMA (ecstasy) intake, human urine contains mostly sulfate and glucuronide conjugates of MDMA metabolites, with sulfates present at higher concentrations than glucuronides. More than 90% of the metabolites DHMA and HMMA were excreted as conjugates. HMMA sulfate had the longest detection window in urine. The ratio of HMMA sulfate to glucuronide was 2.0, and the ratio of DHMA 3-sulfate to 4-sulfate was 5.3 during the first 24 hours, matching predictions from earlier lab experiments. These findings can improve direct urine analysis for MDMA and its metabolites in clinical and forensic toxicology.
Drug Metabolism and Disposition
October 19, 2013
Marta Concheiro, Michael H. Baumann, Karl B. Scheidweiler et al.
32 citations
MDMA, an illicit drug with potential clinical use for PTSD and anxiety, shows nonlinear accumulation in male rats due to metabolic autoinhibition. After doses of 2.5, 5, and 10 mg/kg, MDMA and its metabolite MDA increased more than proportionally with dose, while other metabolites remained constant. Serotonin syndrome severity correlated with MDMA concentrations, and core temperature correlated with MDA concentrations, suggesting distinct mechanisms for behavioral and hyperthermic effects. At 2.5 mg/kg, MDMA Cmax was 164 ± 47.1 ng/ml, with HHMA and HMMA as major metabolites and less than 20% converted to MDA. These findings, given similarities to human pharmacokinetics, support using rat data at clinically relevant doses.
Clinical Chemistry
July 20, 2006
Stéphane Pirnay, T. T. Abraham, Marilyn A. Huestis
29 citations
A sensitive gas chromatography-mass spectrometry method was developed and validated to simultaneously measure MDEA, MDMA, and its metabolites (HMA, MDA, HMMA) in human urine. The method involves acid hydrolysis of 1 mL urine, solid-phase extraction, and derivatization before analysis. Limits of quantification were 25 μg/L for all analytes, with linear calibration up to 5000 μg/L. Extraction efficiencies exceeded 85.5%, and imprecision (coefficient of variation) was below 15% at tested concentrations. The assay meets federal workplace drug testing guidelines for these substances.
Biochemical Pharmacology
September 29, 2011
Andrea E. Schwaninger, Markus R. Meyer, Allan J. Barnes et al.
23 citations
The R- and S-enantiomers of MDMA are eliminated differently in human urine. After controlled oral doses of 1.0 and 1.6 mg/kg, urine from ten participants was analyzed. Over five days, a median of 21% of the measured compounds were excreted as R-stereoisomers and 17% as S-stereoisomers. Significantly more R-enantiomers of MDMA, DHMA, and HMMA sulfate were excreted, while more S-stereoisomers of HMMA and HMMA glucuronide were excreted. No significant differences appeared for MDA and DHMA sulfate. The ratio of R- to S-stereoisomers changed steadily over the first 48 hours, suggesting it could help estimate time of MDMA ingestion in clinical and forensic toxicology.
Journal of Analytical Toxicology
October 1, 2006
Stéphane Pirnay, T. T. Abraham, Richie H. Lowe et al.
23 citations
Acid hydrolysis recovers more MDMA urinary metabolites than enzymatic hydrolysis with beta-glucuronidase from either E. coli or Helix pomatia. Acid hydrolysis yielded 40.0% and 39.3% higher HMA recovery compared to E. coli and H. pomatia hydrolysis, respectively. E. coli beta-glucuronidase gave 17.1% and 26.5% greater MDA recovery than acid hydrolysis and H. pomatia hydrolysis. HMMA recovery by acid hydrolysis was 336.1% and 159.8% greater than E. coli and H. pomatia beta-glucuronidase. Optimal conditions were 100 µL hydrochloric acid per 1 mL urine incubated at 120°C for 40 minutes. Based on recovery, time, availability, and cost, acid hydrolysis is preferred.
International Journal of Molecular Sciences
November 23, 2022
Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli et al.
22 citations
After controlled oral doses of 50–200 mg methylone given to 12 male volunteers, plasma concentrations increased in proportion to dose. Maximum concentrations ranged from 153 ng/mL at the lowest dose to 604 ng/mL at the highest dose. The drug was absorbed rapidly, reaching peak levels in 1.5–2 hours, and had a half-life of about 6 hours. Its metabolite HMMC reached peak concentrations 10–14 times lower than methylone. Unlike MDMA, methylone showed linear pharmacokinetics across the dose range. A validated LC-MS/MS method was used to measure methylone, MDMA, and their metabolites in plasma.
Therapeutic Drug Monitoring
October 1, 2011
Allan J. Barnes, Karl B. Scheidweiler, Erin A. Kolbrich-Spargo et al.
22 citations
Oral fluid testing can detect a single recreational dose of MDMA (70-150 mg) for 1 to 2 days after use. These findings from controlled administration studies give a scientific foundation for interpreting MDMA oral fluid test results.
Journal of Psychoactive Drugs
March 15, 2019
Matthew J. Baggott, Kathleen J. Garrison, Jeremy Coyle et al.
20 citations
The drug MDA, an entactogen similar to MDMA (ecstasy), produces longer-lasting emotional and physiological effects than MDMA. In a controlled experiment with healthy volunteers, a single oral dose of 1.4 mg/kg MDA increased heart rate, blood pressure, and stress hormones (cortisol and prolactin) to levels comparable to those from a 1.5 mg/kg dose of MDMA. However, participants' self-reported drug effects from MDA remained elevated for at least 8 hours, whereas MDMA effects subsided by 6 hours. Blood measurements showed that MDA and its metabolite HMA reached peak concentrations of about 229 µg/L and 92 µg/L, respectively. Because the two drugs had similar blood-level profiles, the longer duration of MDA's effects likely stems from differences in how it acts on the brain rather than from slower elimination.
Metabolites
July 29, 2022
Sara Malaca, Marilyn A. Huestis, Leonardo Lattanzio et al.
8 citations
Synthetic tryptamines like 4-AcO-DiPT are increasingly involved in intoxications and fatalities yet remain unregulated in many countries, with little known about how the body processes them. Using human liver cells and high-resolution mass spectrometry, researchers identified six metabolites formed after three hours of incubation. The main transformation was ester hydrolysis to 4-OH-DiPT, followed by glucuronidation, sulfation, N-oxidation, and N-dealkylation. The most abundant second-generation metabolites were 4-OH-iPT-sulfate and 4-OH-DiPT-glucuronide. The authors suggest that 4-OH-DiPT, 4-OH-iPT, and 4-OH-DiPT-N-oxide are the best biomarkers to detect 4-AcO-DiPT consumption.
Therapeutic Drug Monitoring
May 20, 2015
Dīlek Battal, Allan J. Barnes, Marisol S. Castaneto et al.
6 citations
Mescaline, the psychoactive compound in peyote cactus, has been used for centuries in religious ceremonies. The US military investigated whether mescaline use posed a problem for personnel readiness. Twenty thousand seventeen urine specimens, already negative for other drugs, were screened for mescaline using a biochip array immunoassay. A sensitive gas chromatography-mass spectrometry method was developed and validated for quantification, with a linear range of 1 to 250 mcg/L and high accuracy. Of 526 presumptive-positive and 198 negative specimens tested, none confirmed positive at the quantification limit of 1 mcg/L. Results suggest insufficient mescaline use in the military to warrant routine screening, though stability may have affected prevalence.
Drug Testing and Analysis
March 9, 2024
Marianne Skov‐Skov Bergh, Inger Lise Bogen, Katharina Elisabeth Grafinger et al.
2 citations
N-Ethyl-N-propyltryptamine (EPT), 4-hydroxy-N-ethyl-N-propyltryptamine (4-OH-EPT), and 5-methoxy-N-ethyl-N-propyltryptamine (5-MeO-EPT) are tryptamine-class new psychoactive substances sold online. Their metabolism was previously undescribed. Incubating these compounds with pooled human liver microsomes for up to 4 hours and analyzing with high-performance liquid chromatography and mass spectrometry revealed major metabolic pathways. EPT was primarily metabolized by hydroxylation, N-dealkylation, and carbonylation. 4-OH-EPT metabolism involved double bond formation, N-dealkylation, hydroxylation, and carbonylation. 5-MeO-EPT underwent O-demethylation, hydroxylation, and N-dealkylation. Unique metabolites for 4-OH-EPT were identified in a human postmortem blood sample from a suspected EPT or 4-OH-EPT intoxication, demonstrating the markers' forensic utility.