PubMed · 7640848
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R Hardern, B Tehan. 1995. Ecstasy toxicity.. https://doi.org/10.1136/emj.12.1.74
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3,4-(+/-)-Methylenedioxyamphetamine (MDA) and 3,4-(+/-)-methylenedioxymethamphetamine (MDMA) are serotonergic neurotoxicants. However, when injected directly into brain, MDA and MDMA are not neurotoxic, suggesting that systemic metabolism plays an important role in the development of neurotoxicity. The nature of the metabolite(s) responsible for MDA- and MDMA-mediated neurotoxicity is unclear. alpha-Methyldopamine is a major metabolite of MDA and is readily oxidized to the o-quinone, followed by conjugation with glutathione (GSH). Because the conjugation of quinones with GSH frequently results in preservation or enhancement of biological (re)activity, we have been investigating the role of quinone-thioethers in the acute and long-term neurochemical changes observed after administration of MDA. Although intracerebroventricular (i.c.v.) administration of 5-(glutathion-S-yl)-alpha-methyldopamine (4 x 720 nmol) and 5-(N-acetylcystein-S-yl)-alpha-methyldopamine (1 x 7 nmol) to Sprague-Dawley rats produced overt behavioral changes similar to those seen following administration of MDA (93 mumol/kg, s.c.) they did not produce long-term decreases in brain serotonin (5-hydroxytryptamine, 5-HT) concentrations. In contrast, 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine (4 x 475 nmol) decreased 5-HT levels by 24%, 65% and 30% in the striatum, hippocampus and cortex, respectively, 7 days after injection. The relative sensitivity of the striatum, hippocampus and cortex to 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine was the same as that observed for MDA; the absolute effects were greater with MDA. The effects of 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine were also selective for serotonergic nerve terminal fields, in that 5-HT levels were unaffected in regions of the cell bodies. Because 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine caused long-term depletion in 5-HT without adversely affecting the dopaminergic system, it also mimics the selectivity of MDA/MDMA. The data imply a possible role for quinone-thioethers in the neurobehavioral and neurotoxicological effects of MDA/MDMA.
BACKGROUND: To provide epidemiological information on the extent of design drug use in Spain, the characteristics of users, and the types of substances consumed. MATERIALS AND METHODS: We analyzed two surveys on drug use carried out in 1993 and 1994 (one in the general population older than 15 years and the other in heroin and/or cocaine users who were not in treatment) as well as data on designer drug seizures confiscated by the General Police Headquarters and Ministry of Health laboratories. RESULTS: According to the general population survey, 4.5% of persons 16-40 years of age have tried design drugs at some time, 2.1% more than once, and 0.6% are current users. Design drug use is associated with age of 20-24 years and use of crack (odds ratio [OR] = 28.6), cannabis (OR = 12.5), cocaine (OR = 7.6) or heroin (OR = 3.8). According to the survey of heroin/cocaine users, 25% of cocaine users have used design drugs in the last 30 days, 11% of heroin users, and 18% of those who use both substances. Use is associated with the use of hallucinogens (OR = 4.8), non-use of the injected route (OR = 2), and having been interviewed in recreational areas (OR = 1.8). Police data reflect a stability in the quantities of amphetamines confiscated, a large increase in those of MDMA, and an absence of MDA and MDEA. Ministry of Health laboratories show an increase in confiscations of amphetamines and the presence of MDA, MDMA and MDEA in all years and areas studied, as well as the appearance of MBDB in 1994. CONCLUSIONS: The occasional use of different design drugs has spread to some degree among young people, varies considerably by geographic region, and is associated with the use of other legal and illegal substances, specially stimulants.
Testing human hair for drugs of abuse is a relatively new technique which requires control before being fully accepted in justice applications. Laboratories must be able to demonstrate that they can accurately determine what drugs are present in unknown hair samples and at what levels. To date few exercises have been organized in USA, Germany and France, all devoted to opiates, cocaine and cannabis. However, the number of drugs which can be detected in hair is growing every day. Among them, amphetamine and related compounds, such as MDMA, are of major interest due to increasing abuse. At the initial state of this work, four different preparation procedures were used to test amphetamine, MDA and MDMA. Direct methanol extraction, acid (HCl 0.1 N), alkaline (NaOH 1 N) and enzymatic (beta-glucuronidase/arylsulfatase) hydrolyses were compared. Best recoveries were observed after alkaline hydrolysis. The same hair sample was powdered and sent to 16 laboratories, in USA (4), Germany (6), France (3), Spain (1), Japan (1) and Korea (1) to test amphetamine, methamphetamine, MDA and MDMA. All laboratories returned results within 3 months. Amphetamine tested positive 13 times with concentrations ranging from 3.3 to 17.5 ng/mg. Only 2 laboratories identified methamphetamine, using GC/MS, at low concentration (0.8 and 1.8 ng/mg), which appears to be a false positive. MDA and MDMA both tested positive in 14 cases, with concentrations ranging from 1.8 to 19.5, and 8.9 to 100.0 ng/mg for MDA and MDMA, respectively. These scattered results clearly indicated that new exercises are needed to ensure quality in hair testing. This is one of the major aims of the Society of Hair Testing.