Análisis médico legal de la toxicomanía por MDMA: reporte de caso / Medical-legal relationship of MDMA drug addiction: case report

Resumen El análisis por toxicomanía representa un proceso común solicitado por la Autoridad Judicial para determinar si un usuario presenta hallazgos compatibles con el uso de una droga a nivel clínico, componentes histológicos, patológicos y toxicológicos que puedan generar su uso. Es necesario destacar las limitaciones del ambiente clínico donde se pueden generar múltiples hallazgos, y de la toxicología forense donde a pesar de la especificidad a la que se asocia; también se encuentra limitada por la capacidad de sus equipos tecnológicos. La resonancia magnética nuclear cuantitativa de hidrógeno representa grandes ventajas al demostrar la presencia de una droga ilegal, así como la posibilidad de disminuir costos y tiempo laboral. El uso del MDMA como tratamiento con una reciente aprobación para un estudio de fase III por la FDA, también requiere que se valore el motivo de su uso, por lo que para realizar un análisis médico legal se contemplaron diversos elementos de juicio a fin de satisfacer la evaluación sobre la toxicomanía por MDMA en un usuario que presentó un tejido granular blanco tipo polvo en la sección distal del tabique nasal y negó el consumo de metanfetaminas.

Abstract The analysis for drug addiction represents a common process requested by the Judicial Authority to determine if a user presents findings compatible with the use of a drug at a clinical level, histological, pathological and toxicological components that may generate its use. It is necessary to highlight the limitations of the clinical environment where multiple findings can be generated, and of forensic toxicology where despite the specificity to which it is associated; it is also limited by the capacity of its technological equipment. Quantitative hydrogen nuclear magnetic resonance represents great advantages when demonstrating the presence of an illegal drug, as well as the possibility of reducing costs and labor time. The use of MDMA as a treatment with a recent approval for a phase III study by the FDA, also requires that the reason for its use be assessed, therefore, in order to carry out a legal medical analysis, various elements of judgment were considered in order to satisfy evaluation of MDMA drug addiction in a user who presented with white powder-like granular tissue in the distal section of the nasal septum and denied the use of methamphetamine.

O renascimento dos psicodélicos como potenciais agentes psicoterapêuticos: trajetória, avanços recentes e perspectivas / The renaissance of psychedelics as potential psychotherapeutic agents: trajectory, recent advances and perspectives

Utilizados em vários contextos pela humanidade desde tempos imemoriais até os dias atuais, os psicodélicos despertaram a atenção dos pesquisadores na primeira metade do século passado. Desde então, mesmo com o longo período de restrições às pesquisas científicas devido à implementação da Controlled Substance Act em 1970, inúmeras investigações, principalmente nos últimos anos, vêm indicando o renascimento dos psicodélicos como importantes ferramentas em psicoterapia assistida. Esta revisão narrativa pretende divulgar a trajetória de pesquisa de psicodélicos selecionados (LSD, psilocibina, ayahuasca e MDMA), lançando luz sobre estudos clínicos que indicam a eficácia e a segurança médica dessas substâncias no tratamento de distúrbios mentais como depressão, ansiedade, dependência química e transtorno de estresse pós-traumático. Adicionalmente, também são apontados alguns eventos históricos e culturais relevantes que, de alguma forma, dialogam com esta trajetória.(AU)

Used in various contexts by mankind from immemorial time to nowadays, psychedelics aroused the attention of researchers in the first half of last century. Since then, even with the long period of restrictions on scientific research due to the implementation of the Controlled Substance Act in 1970, accumulated investigations, especially in recent years, have been indicating the renaissance of psychedelics as important tools in assisted psychotherapy. This narrative review intends to disclose the research trajectory of selected psychedelics (LSD, psilocybin, ayahuasca and MDMA) shedding light on clinical studies which support medical efficacy and safety of these substances to treat mental diseases such as depression, anxiety, substance use disorder and post-traumatic stress disorder. Additionally, some relevant historical and cultural events that somehow had dialogued with this trajectory are also approached.(AU)

Utilizados en diversos contextos por la humanidad desde tiempos inmemoriales hasta nuestros días, los psicodélicos despertaron la atención de los investigadores en la primera mitad del siglo pasado. Desde entonces, incluso con el largo período de restricciones en las investigaciones científicas debido a la implementación de la Controlled Substance Act en 1970, numerosas investigaciones, principalmente en los últimos años, han indicado el resurgimiento de los psicodélicos como herramientas importantes en la psicoterapia asistida. Esta revisión narrativa tiene como objetivo dar a conocer la trayectoria de investigación de psicodélicos seleccionados (LSD, psilocibina, ayahuasca y MDMA), arrojando luz sobre estudios clínicos que demuestran la eficacia médica y la seguridad de estas sustancias en el tratamiento de desordenes mentales como la depresión, la ansiedad, dependencia química y trastorno de estrés postraumático. Adicionalmente, también se señalan algunos hechos históricos y culturales relevantes que, de alguna manera, dialogan con esta trayectoria.(AU)

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil

Objective: To conduct Brazil's first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil. Clinical trial registration: RBR-6sq4c9

Long-term treatment with 3, 4-methylenedioxymethamphetamine caused retina damage in C57BL/6 mice / Tratamento a longo prazo com 3, 4-metilenedioximetanfetamina causando dano na retina em camundongos C57BL/6

ABSTRACT Purpose: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. Methods: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. Results: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. Conclusions: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.

RESUMO Objetivos: Como uma classe de drogas psicoesti mulantes, as anfetaminas são amplamente usadas por suas propriedades estimulantes, eufóricas e alucinógenas. Muitos desses efeitos resultam de aumentos agudos na neurotransmissão da dopamina e da serotonina. Após o início desses efeitos, a 3,4-metilenedioximetanfetamina produz danos persistentes nos terminais nervosos de dopamina e serotonina, resultando em neurotoxicidade duradoura. O objetivo desta investigação foi avaliar os efeitos do tratamento baixa dose de metilenedioximetanfetamina na função da retina em camundongos C57BL/6 e seus mecanismos subjacentes. Métodos: Camundongos C57BL/6 foram divididos aleatoriamente em dois grupos (n=10): um grupo foi tratado com solução salina tamponada de fosfato por injeção intraperitoneal diária; o outro grupo foi tratado com 1 mg/kg de metilenedioximetanfetamina por injeção intraperitoneal diária durante 3 meses. Eletroretinografia foi utilizada para testar a função da retina a cada mês. A coloração H&E e análise com deoxinucleotidil terminal transferase foram utilizados para avaliar a morfologia e histologia da retina. Testes de imunoabsorção enzimática foram utilizados para medir marcadores de estresse oxidativo e fatores inflamatórios. A expressão de genes e proteínas foi detectada por PCR em tempo real e western blot. Resultados: O tratamento de três meses com metilenedioximetanfetamina induziu disfunção de retina significativa por apoptose de células fotorreceptoras por estresse oxidativo e resposta inflamatória. Conclusões: Estes resultados sugerem que o tratamento a longo prazo com metilenedioximetanfetamina aumenta as respostas inflamatórias em células fotorreceptoras, resultando em disfunção de retina em camundongos C57BL/6. Assim, a investigação foence uma justificação pré-clínica para os danos na retina causados pelo abuso de metilenedioximetanfetamina.

Identification of the New Psychoactive Substance Dibutylone / 法医学杂志

Objective To establish a method to identify unknown samples based on combined use of gas chromatography-mass spectrometry （GC-MS）, high resolution mass spectrometry （HRMS） and nuclear magnetic resonance spectrum （NMR） technique. Methods The unknown samples were dissolved in methanol solution containing internal standard SKF525A and detected by GC-MS and HRMS. The mixed samples were separated and purified by silica gel column chromatography, and then dissolved in methanol-d4 solution for structural analysis of 1H nuclear magnetic resonance spectroscopy （1H NMR）. Results The characteristic fragment ions （m/z） were 86.1 （base peak）, 71.2, 121.1, and 149.0, and the accurate mass number of molecular ion peak was measured by HRMS to be 236.128 89. By combined use of data analysis and database comparison, a new psychoactive substance of the cathinone class, Dibutylone, was detected in the sample, and the sample also contained a small amount of caffeine. The sample was purified, then identified using 1H NMR, and was further confirmed to be Dibutylone. In addition, the GC-MS retention time and characteristic fragment ions of the main components of the sample were consistent with those of Dibutylone reference material. Conclusion The method established in this study can be used for the identification of Dibutylone in mixed samples.

Epidemiología de las intoxicaciones agudas por drogas de abuso en las urgencias de un hospital del Centro de España basada en datos de análisis toxicológico de orina / Epidemiology of acute poisonings for drugs of abuse in the emergency room of a hospital from the Center of Spain based on analysis data toxicological urine

Introducción: las intoxicaciones agudas son motivo de consulta cada vez más frecuente en los Servicios de Urgencia hospitalarios (SUH) debido a la mayor disponibilidad y acceso a productos químicos tóxicos. Se observan diferentes patrones en cada área sanitaria según el tipo de población, geografía y perfil epidemiológico de consumo. Material y métodos: el objetivo de nuestro estudio es realizar un perfil epidemiológico y describir el manejo del paciente que acude por clínica compatible con intoxicación aguda por drogas de abuso (IA) basado en la determinación de tóxicos en orina para seis sustancias (cannabis, opiáceos, cocaína, anfetaminas, benzodiazepinas y éxtasis) solicitados en el período de estudio 2010-2012. Resultados: se solicitaron 2755 peticiones, de las cuales fueron positivas 1429, y se estudiaron al azar 661 historias clínicas. El perfil de paciente intoxicado de nuestra área es el de varón de entre 30 y 40 años, consumidor preferentemente de cannabis y cocaína; las benzodiazepinas son el tóxico más frecuente en las mujeres, con clínica mayoritariamente neurológica, sin diferencias en cuanto a la franja horaria o el mes del año en que recibió el alta desde el propio SUH en casi el 60% de los casos. Discusión: las IA en los SUH representan casi el 1% de las consultas y tienen una escasa mortalidad. En algunos casos, el médico de urgencias comienza el tratamiento antes de conocer el resultado toxicológico, lo que nos hace plantearnos la utilidad real y el coste-efectividad de estas determinaciones en todos los pacientes con alteración del nivel de conciencia. (AU)

Introduction: acute intoxications are a rising and common query demand on the emergency rooms because of the easy access and disponibility to toxic substances, where we can observe different patterns attending to type of population, geography and epidemiologic consume profile. Material and methods: our objective is to analyze the epidemiology and patient handling coming to the Emergency Room (ER) with compatible symptoms of street drugs abuse, based on the determination of cannabis, cocaine, amphetamine, benzodiazepine, opiates and ectasy urine levels in the period 2010-2012. Results: the ER requested 2755 determinations being positive 1429 and randomly examined 661 clinical histories. The profile of intoxicated patient was male, 30 to 40 years old, preferently cannabis and cocaine consumer (benzodiazepine in women), mostly with neurological symptoms when arrive, without differences between months or day time and, almost 60% of them, discharged directly from the ER. Conclusions: acute intoxications barely represent 1% of ER demands and produce poor or scarce mortality. Sometimes, doctors in charge start with therapeutic measures before knowing the results of toxicology, what leads us to ask about actual usefulness and cost-efficiency of the toxicology assay to every patient with low conscious level. (AU)

Perception of freedom in leisure among substance users and nonusers / Percepção de liberdade no lazer entre usuários e não usuários de substâncias / La percepción de la libertad en el ócio entre usuarios y no usuarios de sustâncias

The aim of this study was to verify that substance use among adolescents would be linked to perceptions of freedom in leisure. It was selected for convenience sampling 186 adolescents at Projeto Quixote in a public school in Guarulhos. It used as questionnaire Data Sociodemographic and Leisure, The Leisure Diagnostic Battery, version B (PLL) to measure Perceived Freedom in Leisure and Drug Use Screening Inventory for classification of substance use, all self-administered. Based on 165 reviews analyzed, the frequency of use of ecstasy and marijuana in the last month were related to higher rates of PLL. The number of substances used in the last month had no significant effect. These data suggest specific components of leisure related to the frequency of substance use, such as perceived control and need at leisure. (AU)

O objetivo deste trabalho foi avaliar se o uso de substâncias entre adolescentes de estaria relacionado relacionado à percepção de liberdade no lazer (PLL). Selecionou-se por conveniência 186 adolescentes no Projeto Quixote e de uma escola estadual de Guarulhos. Utilizou-se o Questionário de Dados Sóciodemográficos e de Lazer, The Leisure Diagnostic Battery, version B (PLL) para mensurar a Percepção de Liberdade no Lazer, e o Drug Use Screening Inventory para classificação do uso de substâncias. Dentre as 165 avaliações analisadas, a frequência do uso de ecstasy e maconha no último mês relacionaram-se com maiores índices do PLL e o número de substâncias usadas no último mês não teve efeito significativo. Os dados indicaram que a frequência do uso de substâncias relaciona-se com subitens do PLL. Observou-se tendência ao aumento do PLL conforme o aumento do uso de substâncias. (AU)

El objetivo de este estudio fue verificar que el uso de sustancias entre los adolescentes podría estar vinculada a la percepción de la libertad en el ocio. Fue seleccionado para el muestreo de conveniencia 186 adolescentes en Proyecto Quijote en una escuela pública de Guarulhos. Se utiliza como cuestionario de datos sociodemográficos y de ocio, la batería de diagnóstico Ocio, versión B (PLL) para medir la percepción de la Libertad en Ocio y Uso de Drogas Inventario de cribado para la clasificación del uso de sustancias, todos los auto-administrado. Basado en 165 comentarios analizan, la frecuencia de uso de éxtasis y marihuana en el último mes se relacionaron con mayores tasas de PLL. El número de sustancias utilizadas en el último mes no tuvo ningún efecto significativo. Estos datos sugieren componentes específicos de ocio relacionadas con la frecuencia de uso de sustancias, como el control percibido y necesitan en el ocio. (AU)

Anxiety and depression symptoms in Brazilian sexual minority ecstasy and LSD users / Sintomas de ansiedade e depressão em brasileiros não heterossexuais usuários de ecstasy e LSD

Abstract Background This study examined drug use patterns and psychiatric symptoms of anxiety and depression among young Brazilian sexual minority ecstasy and LSD users and compared findings with those reported for their heterosexual peers. Method This cross-sectional study employed targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals using an adapted, semi-structured version of the Global Appraisal of Individual Needs questionnaire. The sample comprised 240 male and female young adults who had used ecstasy and/or LSD in the 90 days prior to the interview and who were not on treatment for alcohol and drug abuse. Results Of the 240 subjects enrolled (mean age: 22.9±4.5 years), 28.7% were gay or bisexuals. Multivariate regression analysis showed that the prevalence of depression symptoms in the past 12 months in the sexual minority group was 37% higher than among heterosexuals (prevalence ratio [PR]=1.79; 95% confidence interval [95%CI] 1.03-3.11; p=0.037). Conclusion Strategies should be developed to assess and address individual needs and treatment approaches should be tailored to address depressive symptoms in young, sexual minority club drug users.

Resumo Introdução Este estudo examinou os padrões de uso de drogas e os sintomas psiquiátricos de ansiedade e depressão entre brasileiros não heterossexuais usuários de ecstasy e/ou LSD e comparou os achados com aqueles relatados por seus pares heterossexuais. Método Este estudo transversal empregou amostragens direcionadas e abordagens de mapeamento etnográfico através de entrevistas presenciais realizadas em bares e festivais de música eletrônica usando uma versão adaptada e semiestruturada do questionário de Avaliação Global de Necessidades Individuais. A amostra incluiu 240 adultos jovens do sexo masculino e feminino que haviam usado ecstasy e/ou LSD nos 90 dias anteriores à entrevista e que não estavam em tratamento para abuso de álcool e drogas. Resultados Dos 240 sujeitos incluídos (idade média: 22,9±4,5 anos), 28,7% eram homossexuais ou bissexuais. A análise de regressão multivariada mostrou que a prevalência de sintomas de depressão nos últimos 12 meses no grupo não heterossexual foi 37% superior à dos heterossexuais [razão de prevalência (RP) = 1,79; intervalo de confiança de 95% (IC95%) 1.03-3.11; p=0,037]. Conclusão Estratégias devem ser desenvolvidas para avaliar e abordar as necessidades individuais, e as abordagens de tratamento devem ser adaptadas para sintomas depressivos em usuários de drogas jovens e não heterossexuais.

Intoxicación aguda por MDMA Serie de casos / ACUTE INTOXICATION BY MDMA (ECTASY) REPORT OF 4 CONSECUTIVE PATIENTS

Drugs are a rising problem with today teens. One of these up and coming substances is ectasy. Properly known as MDMA (methyldioxymethamphetamine), is most commonly used at clubes, raves, and atmospheres where there are a lot of people and loud music. MDMA commonly known as ectasy, is a psychoactive drug used as a recreational drug. Desidered effects of its abuse include empathy, euphoria and heightened sensations. When taken by mouth effects begin after 30-45 minutes and lasts 3-5 hours. Adverse effects of MDMA use include addiction, memory problems, paranoia, difficulty sleeping, blurred vision, sweating and a rapid heartheat. Use may also lead to depression and fatigue. Deaths have been reported due to increased body temperature and dehydration. MDMA influences in neurotransmitters serotonin. MDMA generally is illegal in most countries. In general, MDMA users begin reporting effects within 30 to 50 minutes of consumption. The most serious short-term physical health risks of MDMA are hyperthermia and dehydration. Cases of life-threatening or fatal hyponatremia (excessively low sodium concentration in the blood) have developed in MDMA users attemping to prevent dehydration by consuming excessive amount of water without replenishing electrolytes. MDMA overdose intoxication symptoms vary widely due to the involvement of multiple organ system. In most fatalities MDMA was not the only drug involved. Acute toxicity is mainly caused by serotonin syndrome and sympthomimetic effects. MDMA´s toxicity in overdose may be exacerbated by caffeine, with which it is frequently cut (mixed with to increase volume). Caffeine provokes adverse interactions with MDMA ectasy. Polydipsia is another mechanism of hyponatremia after ectasy ingestion. During april 2016, four patients comming from an electronic party were assisted at the Emergentology service from the "Juan Fernandez" hospital from the city of Buenos Aires. The clinical features of these patients are described, and the treatment and the evolution observed, are documented.

Bruxismo secundario al consumo recreacional de éxtasis: revisión de la literatura / Secondary bruxism after recreational ecstasy consumption: a review

El Metilendioximetanfetamina (MDMA) o éxtasis, es una droga sintética que fue accidentalmente aislada en 1914, sin encontrarse en ella una utilidad médica. La OMS la considera una droga psicotrópica y es ilegal en diversos países, incluyendo a Chile. De acuerdo al Estudio Global de Drogas Sintéticas, el consumo de éxtasis ha aumentado considerablemente en Latinoamérica entre el 2008 y 2014, estudios en Chile la muestran con una "nueva droga" cuyo consumo está aumentando en personas de 19­25 años de edad. El concepto de bruxismo en odontología ha cambiado con el paso del tiempo. Actualmente se reconoce su naturaleza multifactorial, en dónde los factores centrales (patofisiología) juegan un rol principal. Diversos autores han reportado bruxismo como un efecto secundario al consumo recreacional de éxtasis, con frecuencias que van entre el 50 a 89%. Esto puede explicarse debido al efecto de desbalance a nivel de las vías serotoninérgicas y/o domaminérgicas que produce el MDMA, tal como parece ocurrir en el bruxismo. Debido a que la Oficina de las Naciones Unidas contra la Droga y el Delito (UNODOC) advierte del aumento progresivo y significativo del consumo de éxtasis en la población joven chilena, es importante conocer las implicancias orales con la finalidad de lograr un mejor manejo odontológico, siendo necesarios mayores estudios para determinar la real asociación entre el consumo de éxtasis recreacional y bruxismo secundario.

Methylenedioxymethamphetamine (MDMA) or Ecstasy is a synthetic drug accidentally isolated in 1914, finding in it no specific medical use. The WHO considers it as a psychotropic drug and it is illegal in several countries, including Chile. According to the Global Synthetic Drugs Assessment, the use of ecstasy has increased steadily in Latin-America between the years 2008 and 2012, and studies in Chile show ecstasy as a "new drug", with an increased consumption in the 19-25 year-old age group. The concept of bruxism in dentistry has changed over time, moving to a multifactorial etiology where central factors, such as pathophysiology have a major role. Several authors report bruxism as a side effect of ecstasy consumption, at a rate of between 50 and 89%. This can be explained by the fact that MDMA acts centrally inducing imbalance at the level of serotonergic and/or dopaminergic pathways, as it occurs in bruxism. Since the United Nations Office on Drugs and Crime warns of a significant and progressive increase in the consumption of recreational ecstasy in young Chilean adult population, it is important to know there are oral implications in order to have better dental management, and further studies are necessary in order to determine an actual association between ecstasy consumption and secondary bruxism.

Dopamine receptors gene expression in male rat hippocampus after administration of MDMA (ecstasy) / La expresión génica de receptores de dopamina en el hipocampo de ratas macho después de la administración de MDMA (éxtasis)

Ecstasy is one of the most popular amusing drugs among young people. Documents indicate some effects of Ecstasy on hippocampus and close relations between dopaminergic functions with reward learning. Therefore, the aim of this study was evaluation of the chronic effects of Ecstasy on memory in male Wistar rats and determination of dopamine receptors' gene expression in hippocampus. Forty adult male Wistar rats randomly distributed in five groups: Control, sham (received 1 ml/kg 0.9% saline) and three experimental groups were: Exp. 1 (2.5 mg/kg), Exp. 2 (5 mg/kg), and Exp. 3 (10 mg/kg) received MDMA intraperitoneally once every 7 days (3 times a day, 3 hours apart) for 4 weeks. Before the first injection animals trained in Shuttle Box memory and tested after the last injection. 24 hours after the final testing, brains of rats were dissected and hippocampus was removed and homogenized. After total RNA extraction and cDNA synthesis, expression of dopamine receptor genes in the hippocampus determined with Real-Time PCR. Our results showed that 2.5 and 5 mg/kg MDMA-treated groups had memory impairment. Also we found that MDMA increased the mRNA expression of dopamine receptors in hippocampus and the highest increase found in dopamine D1 receptors in the 5 mg/kg experimental group. We concluded that low doses of Ecstasy could increase Dopamine takers gene expression in hippocampus and disorder avoidance memory. But in high doses the increase in Dopamine takers gene expression was not as much as that in low doses and avoidance memory disorder was not observed.

El éxtasis es una de las drogas de diversión más populares entre los jóvenes. La investigación reporta algunos de los efectos del éxtasis sobre el hipocampo y la relación entre las funciones dopaminérgicas con la recompensa en el aprendizaje. El objetivo de este estudio fue la evaluación de los efectos crónicos del éxtasis en la memoria de ratas macho Wistar y la determinación de la expresión de genes receptores de dopamina en el hipocampo. Cuarenta ratas macho adultas fueron distribuidas al azar en cinco grupos: grupo control, simulado (a 1 ml/kg 0,9% de solución salina) y tres grupos experimentales: Grupo exp. 1 (2,5 mg/kg), Exp. 2 (5 mg/kg), y Exp. 3 (10 mg/kg) recibió MDMA vía intraperitoneal cada 7 días (3 veces al día, con 3 horas de diferencia) durante 4 semanas. Antes de la primera inyección los animales fueron entrenados en memoria Shuttle Box y examinados después de la última inyección. Veinticuatro horas después de la prueba final, los cerebros de las ratas fueron diseccionados, el hipocampo fue separado y homogeneizado. Después de la extracción total de ARN y síntesis de ADNc, la expresión de genes de los receptores de dopamina en el hipocampo fue determinado con PCR en tiempo real. Nuestros resultados mostraron que los grupos de 2,5 kg y 5 mg/MDMA tratados tenían deterioro de la memoria. Además, encontramos que la MDMA aumentó la expresión de ARNm de los receptores de dopamina en el hipocampo y el aumento mayor se observó en los receptores D1 de dopamina en el 5 mg/kg Grupo experimental. En conclusión, las dosis bajas de éxtasis podrían aumentar tomadores de expresión génica de la dopamina en el hipocampo y trastornos de la memoria. Sin embargo, en dosis altas el aumento de la expresión génica no mostró un aumento significativo, a diferencia de los resultados con dosis bajas, tampoco se observaron trastornos disociativos de memoria.

Association of ecstasy seizure rates with district Human Development Index in the municipality of São Paulo, Brazil, from 2000 to 2007

This study aimed to analyze whether ecstasy consumption is associated with the socioeconomic status in the Municipality of São Paulo, Brazil, from 2000 to 2007. We used an official, reliable and unbiased source supplied by the Department of Narcotics of the State of São Paulo (Denarc) database and the Human Development Index of the districts (HDId) where the seizures occurred. A Spearman correlation test between the average number of ecstasy seizures per million of inhabitants with the HDId was used. There were 190 seizures (totaling 47,934 tablets) spread out in 53 of the 96 districts and 51.6% were concentrated in only 8 districts. The higher rates of ecstasy seizures were directly associated with districts with high HDId that confirmed the association of ecstasy consumption with the socioeconomic status. Itaim-Bibi, Jardim Paulista and Moema were the top three districts with the highest HDId. In these districts, the number of tablets per seizure ranged from as few units to thousands, revealing that not only consumption but also traffic coexist at the same place. Districts with many nightclubs can also influence the incidence of seizures. This knowledge can be useful to help the police from other Brazilian cities to combat ecstasy trafficking.

Este estudo teve como objetivo analisar se o consumo de ecstasy está associado com o nível socioeconômico no Município de São Paulo, Brasil, de 2000 a 2007. Nós usamos uma fonte oficial, confiável e imparcial fornecida pelo banco de dados do Departamento de Narcóticos do Estado de São Paulo (Denarc) e o Índice de Desenvolvimento Humano dos distritos (IDHd), onde as apreensões ocorreram. O teste de correlação de Spearman entre o número médio de apreensões de ecstasy por milhão de habitantes e o IDHd foi utilizado. Houve 190 apreensões (totalizando 47.934 comprimidos) distribuídas em 53 dos 96 distritos e 51,6% concentraram-se em apenas 8 distritos. As maiores taxas de apreensão de ecstasy foram diretamente associadas com distritos com alto IDHd, o que confirmou a associação do consumo de ecstasy com o nível socioeconômico. Itaim Bibi, Jardim Paulista e Moema, distritos como os maiores IDHd, foram os três primeiros colocados. Nesses distritos, o número de comprimidos por apreensão variou de poucas unidades a milhares, revelando que não somente o consumo como também o tráfico coexiste no mesmo local. Distritos com muitas casas noturnas também podem influenciar a incidência de apreensão. Esse conhecimento pode ser útil no auxílio à polícia de outras cidades brasileiras no combate ao tráfico de ecstasy.

[Relationship between problem solving skill and ecstasy usage among adolescents]

Life skills play a significant role in adolescents' health promotion and have a positive effect on modifying their high-risk behaviors. A great deal of studies has shown that problem solving may affect drug usingbehavior. The purpose of this study is to determine adolescents' problem solving skill and its relation with ecstasy usage among adolescents of the west of Tehran. In a cross-sectional [correlative] study. Eight hundred adolescents ranging from 16-18 years old residing in the western public regions of Tehran participated in the study. Problem-solving skill was determined using "problem solving inventory". Adolescents' usage of ecstasy was measured by a self-structured questionnaire. The questionnaires were completed by participants after obtaining an informed consent. Our finding revealed that most of participants [69.4%] enjoyed good problem-solving skills. Also, findings indicated that 7.6% of adolescents have experienced ecstasy usage once at least. There was a significant relationship between problem-solving skill and ecstasy usage in adolescents [P=0.001]. Regarding the findings, it is recommended to reinforce life skills in adolescents by emphasizing the role of parents, peers and friends to prevent substance abuse. It isalso recommended that some programs are required to be executed regarding prohibited substances including ecstasy and their complications to increase publicgeneral information

effect of pentoxifylline on bcl-2 gene expression changes in hippocampus after long-term use of ecstasy in Wistar rats

3,4- Methylenedioxymethamphetamine [MDMA or "Ecstasy"] is a psychoactive and hallucinogenic drug of abuse. MDMA has been shown to produce neurotoxicity both in animals and humans. Recently, the vasodilator drugs such as pentoxifylline is one of the new strategies which have been considered as neuroprotector. In this study effect of pentoxifylline on bcl-2 gene expression changes in hippocampus of rat following long- term use of ecstasy was investigated. 30 male Wistar rats weighing 250-300g were randomly divided into 5 groups: control [normal], sham [MDMA injection], experimental 1[MDMA and then PTX injections], experimental 2[PTX injection and after 1 week, MDMA injection] and vehicle [saline injection] groups. All drugs were injected intraperitoneally. Two weeks later, the hippocampi were removed for studying the changes in bcl-2 gene expression. We used quantitative real time PCR for detection of bcl-2 gene expression in treated groups and then compared them to control samples. The results showed the gene dosage ratio of 0.49, 0.78 and 1.17 for sham, experimental 1 and experimental 2 groups, respectively. The results also showed the bcl-2gene expression declined in sham group as compared to the experimental groups. Furthermore, we observed a significant difference in the bcl-2 gene expression between sham and experimental 2 groups. We conclude that quantitative real time PCR could be used as a direct method for the detection of bcl-2 gene expression in tested and normal samples

Zingiber officinale alters 3,4-methylenedioxymeth amphetamine-induced neurotoxicity in rat brain

The spice Zingiber officinale or ginger possesses antioxidant activity and neuroprotective effects. The effects of this traditional herbal medicine on 3,4-methylenedioxymethamphetamine [MDMA] induced neurotoxicity have not yet been studied. The present study considers the effects of Zingiber officinale on MDMA-induced spatial memory impairment and apoptosis in the hippocampus of male rats. In this experimental study, 21 adult male Sprague Dawley rats [200-250 g] were classified into three groups [control, MDMA, and MDMA plus ginger]. The groups were intraperitoneally administered 10 mg/kg MDMA, 10 mg/kg MDMA plus 100 mg/kg ginger extract, or 1 cc/kg normal saline as the control solution for one week [n=7 per group]. Learning memory was assessed by Morris water maze [MWM] after the last administration. Finally, the brains were removed to study the cell number in the cornu ammonis [CA1] hippocampus by light microscope, Bcl-2 by immunoblotting, and Bax expression by reverse transcription polymerase chain reaction [RT-PCR]. Data was analyzed using SPSS 16 software and a one-way ANOVA test. Escape latency and traveled distances decreased significantly in the MDMA plus ginger group relative to the MDMA group [p<0.001]. Cell number increased in the MDMA plus ginger group in comparison to the MDMA group. Down-regulation of Bcl-2 and up-regulation of Bax were observed in the MDMA plus ginger group in comparison to the MDMA group [p<0.05]. Our findings suggest that ginger consumption may lead to an improvement of MDMA-induced neurotoxicity

Could MDMA promote stemness characteristics in mouse embryonic stem cells via mGlu5 metabotropic glutamate receptors?

Ecstasy, or 3, 4 [+/-] methylenedioxymethamphetamine [MDMA], is a potent neurotoxic drug. One of the mechanisms for its toxicity is the secondary release of glutamate. Mouse embryonic stem cells [mESCs] express only one glutamate receptor, the metabotropic glutamate receptor 5 [mGlu5], which is involved in the maintenance and self-renewal of mESCs. This study aims to investigate whether MDMA could influence self-renewal via the mGlu5 receptor in mESCs. In this expremental study, we used immunocytochemistry and reverse transcription-polymerase chain reaction [RT-PCR] to determine the presence of the mGlu5 receptor in mESCs. The expression of mGlu5 was evaluated after MDMA was added to mESCs throughout neural precursor cell formation as group 1 and during neural precursor cell differentiation as group 2. The stemness characteristic in treated mESCs by immunofluorescence and flow cytometry was studied. Finally, caspase activity was evaluated by fluorescence staining in the treated group. One-way ANOVA or repeated measure of ANOVA according to the experimental design was used for statistical analyses. In this study mGlu5 expression was shown in mESCs. In terms of neuronal differentiation, MDMA affected mGlu5 expression during neural precursor cell formation [group 1] and not during neural precursor differentiation [group 2]. MDMA [450 micro M] induced a significant increment in self-renewal properties in mESCs but did not reverse 2-methyl-6[phenylethynyl] pyridine [MPEP, 1 micro M], a non-competitive selective mGlu5 antagonist. Fluorescence staining with anti-caspase 3 showed a significant increase in the number of apoptotic cells in the MDMA group. We observed a dual role for MDMA on mESCs: reduced proliferation and maintenance of self-renewal. The lack of decreasing stemness characteristic in presence of MPEP suggests that MDMA mediates its role through a different mechanism that requires further investigation. In conclusion, despite being toxic, MDMA maintains stemness characteristics

role of the A2A receptor in cell apoptosis caused by MDMA

Ecstasy, also known as 3, 4-methylenedioxymethamphetamine [MDMA], is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system [CNS]. Withdrawal signs are attenuated by treatment with the adenosine receptor [A2A receptor]. This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. In this experimental study, we used seven groups of Sprague Dawley rats [200-250 g each]. Each group was treated with daily intraperitoneal [IP] injections for a period of one week, as follows: i. MDMA [10 mg/kg]; ii. GCS [0.3 mg/kg]; iii. SCH [0.3 mg/kg]; iv. GCS + SCH [0.3 mg/kg each]; v. MDMA [10 mg/kg] + GCS [0.3 mg/kg]; vi. MDMA [10 mg/kg] + SCH [0.3 mg/kg]; and vi. normal saline [1 cc/kg] as the sham group. Bax [apoptotic protein] and Bcl-2 [anti-apoptotic protein] expressions were evaluated by striatum using RT-PCR and Western blot analysis. There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group [p<0.05]. A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor [GCS] decreases the cytotoxcity of MDMA, while the antagonist of this receptor [SCH] increases its cytotoxcity