Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns

ABSTRACT This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

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.

Study the effect of 3,4-Methylenedioxy methamphetamine on cytochrome P450 2E1 activity

Abstract Evaluating the effects of ecstasy on CYP2E1 activity is of great concern, mainly due to growing trends in abuse and co-administration of MDMA with ethanol and the dominant role of this isoenzyme on ethanol metabolism. This study aimed to evaluate the effects of MDMA on CYP2E1 activity. A total of 24 male rats were selected and divided into three groups. The first and second groups consisted of 12 rats and were employed to optimize the perfusion method, and the third group was employed for studying the alteration of CYP2E1 activity after liver exposure to MDMA (300 and 600 ng/ml). The amount of chlorzoxazone and 6-hydroxy chlorzoxazone in a sample obtained from liver perfusion before and after exposure to a buffer containing MDMA was determined by HPLC-FL. The enzymatic activity of rat CYP2E1 decreased after liver perfusion with a buffer containing 600 ng/ml of MDMA. However, no significant changes were observed in chlorzoxazone and 6-hydroxy chlorzoxazone concentration in perfusate before and after liver perfusion with a buffer containing 300 ng/ml of MDMA. Our findings suggest that the activity of CYP2E1 in rats might decrease only after administration of MDMA at a lethal dose. However, further animal and human studies are needed to confirm our assumption.

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

Detection of ketamine, MDMA and their main metabolites in urine samples by SPME-HPLC-MS / 中国药科大学学报

@#To establish a method for the determination of ketamine and MDA and their main metabolites in urine by solid phase microextraction-liquid chromatography-mass spectrometry. In a urine sample supplemented with quantitative ketamine, norketamine, MDMA and MDA control. The solution was adjusted pH 11, added solid Na2CO3, heated and stirred at 60 °C. Then, the sample was extracted by SPME with 60 μm polydimethylsiloxane-vinylbenzene copolymer(PDMS/DVB ), a middle-polar coated fiber for 15 minutes and then analyzed by HPLC-MS. The result showed good linearity in the range of 0. 03-1. 0 μg/mL, r≥0. 999 2, and LOD was 0. 01 μg/mL, the value of the average recovery rate was varying from 97. 19%-105. 44%, and RSD was within 10%. The method is simple, safe and accurate, and can be used to determine ketamine, MDMA and their main metabolites in urine.

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.

Usos terapéuticos de sustancias prohibidas: LSD, MDMA, THC, GHB, DMT, psilocybina y mescalina / Therapeutic uses of prohibited substances: LSD, MDMA, THC, GHB, DMT, psilocybin, mescaline

El presente texto hace un breve recorrido sobre los usos terapéuticos que han tenido la LSD, MDMA, THC, GHB, DMT, Psilocybina y Mescalina en la historia, así como también refiere algunos de los beneficios para la salud física y mental que se considera tienen en la actualidad. Esta información científica se contrapone a la normativa internacional en materia de drogas, que las clasifica como sustancias prohibidas en la Lista I, debido a su falta de uso médico aceptado por Estados Unidos y a su alto potencial de abuso. En este trayecto también se intenta comprender a qué hace referencia dicho potencial, así como las motivaciones que podrían existir detrás de la prohibición del uso terapéutico de estas drogas. En este marco, se consideran consecuencias para la salud de la población, las que atentan contra los Derechos Humanos de las personas que podrían requerir alguna de estas sustancias.

This paper makes a brief of the therapeutic uses have had the LSD, MDMA, THC, GHB, DMT, Psilocybin and Mescaline in history, as well as some of the benefits referred to physical and mental health that are considered today. This scientific information seems contrary to international legislation on drugs, which classifies as prohibited substances in Schedule I, due to its lack of acceptance medical use by the United States and its high potential for abuse. In this way also try to understand what makes this potential reference, and the reasons that could be behind the ban on therapeutic use of these drugs. In this framework, we consider health consequences of the population, which violate the human rights of people who may require some of these substances.

ST elevation myocardial infarction in a young patient after ingestion of caffeinated energy drink and ecstasy / 世界急诊医学杂志（英文）

BACKGROUND: Caffeinated energy drinks are widely used worldwide. They are associated with a variety of adverse effects and are of concern to health authorities, yet there is still scarce information about their adverse effects and inadequate awareness among medical personnel. METHODS: Case description and discussion of a patient presenting to the emergency room after overdose of energy drinks in combination with 3,4-methylenedioxymethamphetamine (MDMA). RESULTS: Despite best medical efforts, the patient died of fatal cardiac arrhythmias. There is a paucity of information about adverse effects of energy drinks. CONCLUSION: Although energy drinks are widely used, there is a lack of awareness in the population and medical staff about their hazards.

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure

The so-called "club drug" Foxy or Methoxy Foxy (5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride; 5-MeO-DIPT) is a newer drug of abuse that has recently gained in popularity among recreational users as an alternative to MDMA (Ecstasy). While considerable research into the consequences of MDMA use is available, much remains unknown about the neurobiological consequences of 5-MeO-DIPT use. In the present study, beginning at 35 days of age adolescent rats were given repeated injections of 10 mg/kg of 5-MeO-DIPT, MDMA, or a corresponding volume of isotonic saline. Adult animals (135 days old) were trained and tested on a number of tasks designed to assess the impact, if any, and severity of 5-MeO-DIPT and MDMA, on a series of spatial and nonspatial memory tasks. Both the 5-MeO-DIPT- and the MDMA-treated rats were able to master the spatial navigation tests where the task included a single goal location and all groups performed comparably on these phases of training and testing. Conversely, the performance of both groups of the drug-treated rats was markedly inferior to that of the control animals on a task where the goal was moved to a new location and on a response learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. In addition, in a response learning version of a learning set task, 5-MeO-DIPT rats made significantly more working memory errors than MDMA or control rats. Results are discussed in terms of observed alterations in serotonin activity in the forebrain and the consequences of compromised serotoninergic systems on cognitive processes.

Análises físicas e químicas de comprimidos de ecstasy apreendidos no município de São Paulo / Physical and chemical analyses of ecstasy tablets seized in São Paulo city

Drug profiling, isto é, a caracterização de amostras de drogas apreendidas no sentido de estabelecer conexões entre apreensões realizadas em diferentes épocas e/ou locais a uma origem comum de produção clandestina, tem sido um objetivo dos órgãos governamentais responsáveis pela prevenção/repressão. Especificamente tratando-se de comprimidos de ecstasy, o conhecimento de suas propriedades físicas e químicas é de relevante importância para discriminar a apreensão de diferentes lotes. Nesse contexto, o presente trabalho propõe uma nova abordagem para estabelecer conexões entre apreensões de comprimidos de ecstasy, por meio da calorimetria exploratória diferencial (DSC), termogravimetria (TG) e difratometria de raios-X (DRX). Também foi realizada a caracterização física de todos os comprimidos (logotipo, coloração, massa, diâmetro e espessura), bem como a identificação/quantificação dos constituintes ativos por cromatografia em fase gasosa acoplada à espectrometria de massas (GC-MS) e o perfil de dissolução in vitro. Além disso, foi desenvolvido um método empregando a extração líquido-líquido para o isolamento da 3,4-metilenodioximetanfetamina (MDMA) dos comprimidos de ecstasy, que posteriormente foi cristalizada para cloridrato de MDMA (MDMA.HCl). Foram analisados dezessete diferentes lotes de comprimidos de ecstasy de diversos logotipos e colorações apreendidos no município de São Paulo, Brasil. Apenas um lote apresentou como única substância ativa a clorofenilpiperazina (CPP). Os outros continham apenas MDMA e o conteúdo de MDMA variou de 29 a 115-mg/comprimido. Os valores de massa dos comprimidos variaram de 143 a 341-mg, a espessura de 3,2 a 5,8-mm e o diâmetro de 7,0 a 9,5-mm. A comparação das curvas obtidas, tanto por calorimetria exploratória diferencial (DSC) como pelos difratogramas de raios-X (DRX), permitiu discriminar aqueles com perfis semelhantes, importante para identificar a origem de produção. O baixo grau de cristalinidade do MDMA.HCl de alguns comprimidos de ecstasy não impediu a caracterização por DSC e DRX. Esses resultados podem ser úteis para a aplicação no trabalho de inteligência forense

Drug profiling or the characterization of seized drug samples to link seizures made at different times and/or locations to their common clandestine origin, has long been a goal of law enforcement agencies. Considering the trafficking of ecstasy tablets, the knowledge of chemical and physical properties is of utmost importance to discriminate between different seizures. In this context this study proposed a new approach to establish links among seizures of ecstasy tablets by using differential scanning calorimetry (DSC), thermogravimetry (TG) and X-ray diffraction (XRD). Besides this characterization, physical appearance (logotype, color, weight, diameter and thickness), identification/quantification of active constituents by gas chromatography/ mass spectrometry (GC/MS) and in vitro drug dissolution assays were performed too. A method employing liquid-liquid extraction was also developed for the isolation of 3,4-methylenedioxymethamphetamine (MDMA) from ecstasy tablets and afterwards MDMA was crystallized to MDMA hydrochloride (MDMA.HCl). Seventeen different lots of various logotypes and colors of confiscated ecstasy tablets from seizures in São Paulo city, Brazil, were analyzed. Chlorophenylpiperazine (CPP) was found only as an active ingredient in one batch. The others tablets contained only MDMA and the content of MDMA varied from 29 to 115-mg/tablet. The weight values of tablets varied from 143 to 341-mg, the thickness from 3,2 to 5,8-mm and the diameter from 7,0 to 9,5-mm. DSC/TG curves and X-ray difratograms of the ecstasy tablets allowed distinguishing those with similar profile, for both techniques, which is important to identify the source of production. The low degree of MDMA.HCl crystallinity of some ecstasy tablets didnt prevent DSC and XRD characterization. These results can be useful for forensic intelligence work application

Genotoxicity Study of Illegal Drug MDMA and Its Nitroso Derivative N-MDMA by Micronucleus and Chromosomal Aberration Tests using Chinese Hamster Lung Fibroblast Cell Line

Objectives: An increase in incidence of the illegal use of tablets containing 3,4-methylenedioxymethamphetamine hydrochloride (MDMA) has recently become a widespread social problem. MDMA ingested orally reacts with nitrite in the stomach and is synthesized into N-nitroso-3,4-methylenedioxymethamphetamine (N-MDMA). The aim of this study is to investigate the genotoxic effects of MDMA and N-MDMA on the basis of the results of an in vitro micronucleus (MN) test and an in vitro chromosomal aberration (CA) test using a Chinese hamster lung fibroblast cell line (CHL/IU). Methods: Tablets containing MDMA obtained from the Regional Bureau of the Ministry of Health, Labor and Welfare were purified, and N-MDMA was synthesized from MDMA in our laboratory. To evaluate the effects of MDMA and N-MDMA, the MN test established by our laboratory and the CA test in accordance with the guidelines for toxicity studies of drugs recommended by the Ministry of Health, Labor and Welfare were performed. Results: In the MN test, no increased frequency of MNs was not found for MDMA. On the other hand, an apparently increased frequency of MNs was observed for N-MDMA. In the CA test, no CA was found for MDMA, but CA was observed for N-MDMA apparently. Conclusion: N-MDMA genotoxicity was observed in the MN and CA tests. However, no MDMA genotoxicity was observed.

Geonotoxicity study of illegal drug MDMA and its nitroso derivative N-MDMA by micronucleus and chromosomal aberration tests using Chinese hamsger lung fibroblast cell line

<p><b>OBJECTIVES</b>An increase in incidence of the illegal use of tablets containing 3,4-methylenedioxymethamphetamine hydrochloride (MDMA) has recently become a widespread social problem. MDMA ingested orally reacts with nitrite in the stomach and is synthesized intoN-nitroso-3,4-methylenedioxymethamphetamine (N-MDMA). The aim of this study is to investigate the genotoxic effects of MDMA and N-MDMA on the basis of the results of an in vitro micronucleus (MN) test and an in vitro chromosomal aberration (CA) test using a Chinese hamster lung fibroblast cell line (CHL/IU).</p><p><b>METHODS</b>Tablets containing MDMA obtained from the Regional Bureau of the Ministry of Health, Labor and Welfare were purified, and N-MDMA was synthesized from MDMA in our laboratory. To evaluate the effects of MDMA and N-MDMA, the MN test established by our laboratory and the CA test in accordance with the guidelines for toxicity studies of drugs recommended by the Ministry of Health, Labor and Welfare were performed.</p><p><b>RESULTS</b>In the MN test, no increased frequency of MNs was not found for MDMA. On the other hand, an apparently increased frequency of MNs was observed for N-MDMA. In the CA test, no CA was found for MDMA, but CA was observed for N-MDMA apparently.</p><p><b>CONCLUSION</b>N-MDMA genotoxicity was observed in the MN and CA tests. However, no MDMA genotoxicity was observed.</p>