MDMA (Ecstasy) neurotoxicity: assessing and communicating the risks

MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine analogue that produces euphoric and stimulant effects and a feeling of closeness towards others.1 and 2 For more than a decade, MDMA (colloquially known as “Ecstasy” or “E”) has been widely used by young adults as a dance-party drug. The usual recreational oral dose is 1-2 tablets (each containing about 60-120 mg of MDMA) a standard oral dose of 0·75–4·00 mg per kg in 60–80 kg people. MDMA is typically used once fortnightly or less because tolerance to the effects of MDMA develops rapidly. More frequent use requires larger doses to achieve the desired effects, but this increases the prevalence of unpleasant side-effects.3 A number of deaths have occurred as a result of malignant hyperthermia or idiosyncractic reactions to the drug, but these have been rare.4 MDMA is perceived by many users to be a safe drug.1 Few report the craving associated with opiates or cocaine3 and most MDMA users are aware of only mild and transient disruptions of functioning.3 and 5 AC Parrott and J Lasky, Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance, Psychopharmacology 139 (1998), pp. 261–268. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (174)5 The perceived safety of MDMA is at odds with animal evidence of MDMA neurotoxicity, an increasing prevalence of hazardous patterns of use among recreational MDMA users, and emerging evidence of neurotoxicity among heavier MDMA users.

Disposition of MDMA and Metabolites in Human Sweat Following Controlled MDMA Administration

BACKGROUND: Understanding the excretion of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites in sweat is vital for interpretation of sweat tests in drug treatment, criminal justice, and workplace programs. METHODS: Placebo, low (1.0 mg/kg), and high (1.6 mg/kg) doses of oral MDMA were given double-blind in random order to healthy volunteers (n = 15) with histories of MDMA use. Participants resided on the closed clinical research unit for up to 7 days after each dose. Volunteers wore PharmChek (R) sweat patches (n = 640) before, during, and after controlled dosing. Patches were analyzed by solid phase extraction and GC-MS for MDMA, methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 4hydroxy-3-methoxymethamphetamine (HMMA). Limits of quantification (LOQ) were 2.5 ng/patch for MDMA and 5 ng/patch for HMA, HMMA, and MDA. RESULTS: MDMA was the primary analyte detected in 382 patches (59.7%), with concentrations up to 3007 ng/patch. MDA was detected in 188 patches (29.4%) at <172 ng/patch, whereas no HMMA or HMA was detected; 224 patches (35.0%) and 60 patches (9.4%) were positive for MDMA and MDA, respectively, at the 25-ng/patch threshold proposed by the Substance Abuse and Mental Health Services Administration. CONCLUSIONS: Sweat testing was shown to be an effective and reliable method for monitoring MDMA use in this controlled MDMA administration study. However, variability in sweat excretion suggests that results should be interpreted qualitatively rather than quantitatively. These data provide a scientific database for interpretation of MDMA sweat test results. (C) 2008 American Association for Clinical Chemistry

O Branqueamento de capitais e a droga

Mestrado em Contabilidade

"Êxtase": revisão farmacológica

Neste estudo fez-se uma revisão bibliográfica sobre a 3,4- metilenodioximetan-fetamina (MDMA), mais conhecida como "êxtase", uma droga em expansão de abuso entre os jovens. Descreve-se o histórico, desde sua síntese até seu uso inicial como auxiliar em psicoterapia e, mais recentemente, como droga de abuso. Apresenta-se o perfil de uso em outros países, tentando prever o possível padrão de uso no Brasil, onde já se iniciou o abuso. O detalhamento sobre a farmacocinética da MDMA visa a justificar as conseqüências sobre a atividade farmacológica e toxicológica. Resumem-se as manifestações clínicas de toxicidade a curto e a médio prazo, descrevendo-se os efeitos na intoxicação grave com o "êxtase". São apresentados os estudos dos mecanismos de ação no sentido de justificar seus efeitos tóxicos psíquicos e físicos, detalhar os mecanismos pelos quais a droga é auto-administrada e as possibilidades terapêuticas para reverter os efeitos.

Festa e droga: circustâncias dos consumos de substâncias psícoactivas ilícitas na população portuguesa

Parece à primeira vista contraditório estabelecer uma conjunção entre a festa e a droga que o discurso cultural tradicional avaliam de forma bem diferente, pelo menos se associarmos as drogas às substâncias consideradas mais perigosas, potencialmente e, por isso, classificadas como sendo ilícitas. A associação já pareceria perfeitamente aceitável se por "drogas" nos referíssemos ao tabaco mas, sobretudo ao álcool. Festa, digna desse nome, como qualquer celebração, inclui sempre um momento para o brinde, que não se faz sem "um copo", desde o copo de "vinho doce", guardado no armário das nossas infâncias, na expectativa de qualquer bom acontecimento - que muitas vezes tardava - até ao copo de cidra - "sem álcool" - com o qual se socializam os nossos filhos à estéfica da festa, passando pelo "copo" que é, ele mesmo, o pretexto para a "festa". Drogas ilícitas, no entanto, estão mais conotadas com o risco, com a desgraça-que-se-espera-nunca-bata-à-nossa- -porta, com a miséria... No plano do discurso institucional, a droga aparece também conotada negativamente, primeiro, através da figura da delinqüência, presente já na ilegalidade do acto que o consumo representa e, em seguida, considerando as circunstâncias que acompanham a aquisição da substância, depois através da figura da doença, que acabou por se impor ulfimamente.

Estratégias desenvolvidas por usuários de crack para lidar com os riscos decorrentes do consumo da droga

OBJETIVOS: O objetivo deste estudo foi identificar, sob a ótica de usuários de crack, quais são as estratégias que eles utilizam para minimizar ou evitar os riscos decorrentes do consumo de crack. MÉTODO: Utilizou-se método qualitativo de pesquisa, desenvolvido mediante entrevistas semiestruturadas em profundidade. Foi entrevistada uma amostra intencional por critérios, composta por 30 usuários de crack, selecionados por meio de informantes-chave e distribuídos em oito diferentes cadeias. As entrevistas foram transcritas literalmente, inseridas e analisadas no software NVivo 8, com exploração dos dados mediante a técnica de análise de conteúdo. RESULTADOS: Os entrevistados acreditam que os maiores riscos decorrentes da dependência do crack sejam os relacionados aos efeitos psíquicos da droga, como fissura, sintomas paranoides transitórios e sintomas depressivos, assim como os decorrentes da ilegalidade dela, como a polícia e as questões referentes ao tráfico. Entretanto, os riscos de complicações físicas do consumo quase não foram apontados. As estratégias se concentraram no controle dos efeitos psíquicos, principalmente pelo consumo de álcool e maconha. Para lidar com as consequências da ilegalidade da droga, mostraram se preocupar com a postura que adotam perante o traficante e a polícia. CONCLUSÕES: As estratégias desenvolvidas pelos usuários focam na tentativa de se autoprotegerem principalmente dos episódios de violência e no alívio de sintomas desagradáveis causados pela droga - principalmente fissura e sintomas paranoides transitórios. Essas estratégias podem parecer efetivas a curto prazo, porém apresentaram riscos de longo prazo, tais como dependência de álcool e maconha.

The profiling of MDMA tablets: a study of the combination of physical characteristics and organic impurities as sources of information

The profiling of MDMA tablets can be carried out using different sets of characteristics. The first type of measurements performed on MDMA tablets are physical characteristics (i.e. post-tabletting characteristics). They yield preliminary profiling data that may be valuable in a first stage for investigation purposes. However organic impurities (i.e. pre-tabletting characteristics) are generally considered to bring more reliable information, particularly for presentation of evidence in court. This work aimed therefore at evaluating the added value of combining pre-tabletting characteristics and post-tabletting characteristics of seized MDMA tablets. In approximately half of the investigated cases, the post-tabletting links were confirmed with organic impurities analyses. In the remaining cases, post-tabletting batches (post-TBs) were divided in several pre-tabletting batches (pre-TBs), thus supporting the hypothesis that several production batches of MDMA powder (pre-TBs) were used to produce one single post-TB (i.e. tablets having the same shape, diameter, thickness, weight and score; but different organic impurities composition). In view of the obtained results, the hypotheses were discussed through illustrating examples. In conclusion, both sets of characteristics were found relevant alone and combined together. They actually provide distinct information about MDMA illicit production and trafficking.

Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

INTRODUCTION Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. METHODS Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. RESULTS The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. CONCLUSIONS Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humans.

This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.

Interferência do intervalo de administração da droga sobre a nefrotoxicidade da gentamicina em ratos

A insuficiência renal aguda (IRA) que apresenta índice de mortalidade em torno de 50%, pode ser definida como um abrupto declínio da filtração glomerular, resultante de isquemia ou toxicidade. A nefrotoxicidade por drogas é uma das etiologias mais freqüentes (27%) e sugere-se que o intervalo de administração da droga pode interferir neste efeito colateral, entretanto o melhor regime de administração ainda não está bem estabelecido. Este conhecimento proporcionaria uma atuação mais direcionada de enfermagem na prevenção desta IRA hospitalar. Os resultados obtidos nesta pesquisa, indicam que a infusão única de gentamicina determina menor nefrotoxicidade, provavelmente devido à redução da sua concentração plasmática nas 24hs, diminuindo o acúmulo intracelular deste fármaco, um dos principais mecanismos celulares deste tipo de lesão. Este regime de tratamento mostra portanto vantagens quanto ao custo, efeito nefrotóxico e segurança quanto à eficácia terapêutica.

Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans.

BACKGROUND AND PURPOSE: The use of ± 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is associated with cardiovascular complications and hyperthermia. EXPERIMENTAL APPROACH: We assessed the effects of the α(1) - and β-adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, four-period crossover design. KEY RESULTS Carvedilol reduced MDMA-induced elevations in blood pressure, heart rate and body temperature. Carvedilol did not affect the subjective effects of MDMA including MDMA-induced good drug effects, drug high, drug liking, stimulation or adverse effects. Carvedilol did not alter the plasma exposure to MDMA. CONCLUSIONS AND IMPLICATIONS: α(1) - and β-Adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychotropic effects. Carvedilol could be useful in the treatment of cardiovascular and hyperthermic complications associated with ecstasy use.