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Therapeutic Drug Monitoring

ISSN 0163-4356

13 papers in the library · 1,439 citations · publishing 1996-2015

Papers

Human Pharmacology of MDMA

Therapeutic Drug Monitoring March 19, 2004 Rafael de la Torre, Magı́ Farré, Pere N. Roset et al. 445 citations

MDMA (ecstasy) is a widely misused psychostimulant that increases energy, euphoria, and sociability while also producing distinctive 'entactogen' effects such as feeling close to others and increased empathy. It works by promoting the release and blocking the reuptake of serotonin, dopamine, and norepinephrine. Acute toxic effects include serotonin syndrome, characterized by muscle rigidity, hyperreflexia, and hyperthermia. MDMA metabolism involves two main pathways; one is partially regulated by the polymorphic enzyme CYP2D6, but mechanism-based inhibition after two consecutive doses limits the impact of CYP2D6 genetics on acute toxicity. Metabolism may also contribute to long-term neurotoxic effects through progressive degeneration of the serotonergic system.

Toxicokinetics of Amphetamines: Metabolism and Toxicokinetic Data of Designer Drugs, Amphetamine, Methamphetamine, and Their N-Alkyl Derivatives

Therapeutic Drug Monitoring April 1, 2002 Thomas Kræmer, Hans H. Maurer 232 citations

Amphetamines and related designer drugs are metabolized primarily by cytochrome P450 enzymes, with many N-alkylated derivatives acting as prodrugs that convert to active amphetamine or methamphetamine. The review covers MDA, MDMA, MDE, BDB, MBDB, and several N-alkylated amphetamines including methamphetamine, benzphetamine, and selegiline. It summarizes findings from English-language publications between 1995 and 2000 on metabolite identification, cytochrome P450-dependent metabolism, and pharmacokinetic or toxicokinetic data. The implications of these toxicokinetic pathways for forensic toxicology and interpretation in legal cases are discussed.

Chemistry, Pharmacology, Toxicology, and Hepatic Metabolism of Designer Drugs of the Amphetamine (Ecstasy), Piperazine, and Pyrrolidinophenone Types

Therapeutic Drug Monitoring March 19, 2004 Hans H. Maurer, Thomas Kræmer, Dietmar Springer et al. 147 citations

Designer drugs such as MDMA, MDEA, MDA, and various piperazine and pyrrolidinophenone compounds, often used as rave drugs, produce euphoria, energy, and sociability. Despite their reputation as safe, studies in rats and primates along with human epidemiological investigations indicate potential risks, including serotonin syndrome, liver toxicity, neurotoxicity, and psychological problems. Metabolites may contribute to some toxic effects, so understanding metabolism is crucial for risk assessment. The enzyme CYP2D6, which is polymorphically expressed, catalyzes the major metabolic steps of piperazine- and pyrrolidinophenone-derived designer drugs, though it remains unclear whether this genetic polymorphism is clinically relevant.

Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine After Controlled Oral Administration to Young Adults

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.

The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity

Therapeutic Drug Monitoring March 19, 2004 Terrence J. Monks, Douglas C. Jones, Fengju Bai et al. 123 citations

MDA and MDMA (ecstasy) are amphetamine derivatives that combine stimulant and hallucinogenic effects and are used recreationally despite warnings of irreversible damage to the central nervous system. They are primarily serotonergic neurotoxicants. Because neither drug causes neurotoxicity when injected directly into the brain, and certain major metabolites also fail to reproduce this effect, researchers investigated the role of thioether metabolites of alpha-methyldopamine and N-methyl-alpha-methyldopamine. These thioether conjugates stimulate acute release of serotonin, dopamine, and norepinephrine, produce behavioral signs of serotonin syndrome, and when injected into rat brain cause long-term serotonin depletion, increased GFAP expression, and microglial activation. The evidence suggests these thioether metabolites contribute to the neurotoxicity of the parent amphetamines.

On the Metabolism and the Toxicological Analysis of Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography-Mass Spectrometry

Therapeutic Drug Monitoring August 1, 1996 Hans H. Maurer 111 citations

Designer drugs of the methylenedioxyphenylalkylamine type, such as MDA, MDMA, MDE, BDB, and MBDB, are increasingly abused. Their metabolism in humans involves two overlapping pathways: O-dealkylation of the methylenedioxy group to dihydroxy derivatives followed by methylation of one hydroxy group, and successive side-chain degradation to N-dealkyl and deaminooxo metabolites. MDA, MDMA, and MDE are further metabolized to glycine conjugates of 3,4-disubstituted benzoic acids. A gas chromatography–mass spectrometry (GC-MS) screening procedure was developed to detect these drugs and their metabolites in urine after acid hydrolysis, isolation at pH 8-9, and acetylation. Using mass chromatography with characteristic fragment ions, the method can detect abuse or intoxication at 5-50 ng/ml.

Drugs of Abuse Monitoring in Blood for Control of Driving Under the Influence of Drugs

Therapeutic Drug Monitoring April 1, 2002 Manfred R. Moeller, Thomas Kraemer 98 citations

Driving under the influence of drugs is a growing concern in industrialized countries, contributing to road accidents. In forensic toxicology, the increasing number of blood samples for drug testing results from zero-tolerance laws and better-trained police officers. This review describes procedures for detecting amphetamine, methamphetamine, MDMA, MDEA, MDA, cannabinoids (THC and its metabolites), cocaine and its metabolites, opiates (heroin, 6-monoacetylmorphine, morphine, codeine), methadone, GHB, LSD, PCP, and psilocybin/psilocin in whole blood, plasma, and serum. Sensitive immunologic screening methods are available for many analytes. Gas chromatography-mass spectrometry remains the gold standard for confirmatory analysis, with liquid chromatography-mass spectrometry also included. Two tables summarize basic data on biosample, internal standard, workup, column, mobile phase, detection mode, and validation.

Fungal Hallucinogens Psilocin, Ibotenic Acid, and Muscimol

Therapeutic Drug Monitoring July 12, 2013 Katarzyna Stebelska 73 citations

Psilocin, ibotenic acid, and muscimol, psychoactive compounds from fungi, have been used recreationally since the 1960s despite documented neurotoxicity and a reputation as safe and nonaddictive. Scientific efforts to find medical applications in psychiatry, psychotherapy, and religious rituals remain controversial; any healing potential may be inadequate and could harm patients. While hallucinogens generally reduce cognitive functions, recent findings suggest psilocin might improve perception and mental skills, motivating magic mushroom use. This article reviews symptoms of intoxication, analytical detection methods in fungal material, food, and body fluids, mechanisms of biological activity, therapeutic potential, and health risks of abuse.

3,4-Methylenedioxymethamphetamine (MDMA) Intoxication in an Infant Chronically Exposed to Cocaine

Therapeutic Drug Monitoring July 22, 2005 Óscar García‐algar, Nuria L Pez, M. Á. Bonet et al. 39 citations

An infant admitted to a pediatric emergency department had accidentally ingested MDMA (ecstasy), detected through urine drug testing. The infant's hydrolyzed urine contained 11.7 mg/L of MDMA and 34.4 mg/L of its main metabolite HMMA. Symptoms including apparent febrile convulsions and cardiovascular side effects resolved within one day after treatment with benzodiazepines. Segmental hair analysis also revealed chronic exposure to cocaine. The mother consistently denied any drugs in the home, complicating diagnosis. Periodic clinical and laboratory follow-ups were recommended to monitor long-term effects of illicit drug exposure and to ensure the child's removal from dangerous environments.

MDMA and Metabolite Disposition in Expectorated Oral Fluid After Controlled Oral MDMA Administration

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.

Determination of LSD in Urine With High-Performance Liquid Chromatography–Mass Spectrometry

Therapeutic Drug Monitoring August 1, 2001 Karl Bodin, Jan‐olof Svensson 11 citations

A method using high-performance liquid chromatography and mass spectrometry can reliably detect LSD in urine at concentrations as low as 0.02 ng/mL. The procedure involves extracting LSD from urine into an organic solvent, then back-extracting into an acetate buffer, followed by separation and detection. A trideuterated form of LSD serves as an internal standard to improve accuracy. The method shows consistent results, with measurement variability of 3.5% within a day and 4.0% between days, and recovers 91% of LSD from samples. The calibration curve is linear across 0.05 to 10 ng/mL, making it suitable for routine testing.

Urine Mescaline Screening With a Biochip Array Immunoassay and Quantification by Gas Chromatography–Mass Spectrometry

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.