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Wieliczko, Monika J. "Psychological effects of MDMA." Thesis, Canterbury Christ Church University, 2016. http://create.canterbury.ac.uk/14928/.
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Zinberg's Interaction Model implies that the content of a drug-induced experience is a function of the pharmacological properties of the drug, the set (the user’s characteristics e.g. motivation and personality), and the setting (the physical and social context). The current research investigated the function of the set and setting and their role in shaping the psychological effects of 3,4-methylenedioxmethamphetamine (MDMA), as well as their role in reducing the risk of drug abuse. An online survey was distributed among adult MDMA polydrug users (n = 158) and MDMA-naïve controls (alcohol, nicotine and cannabis users, n = 138). Participants answered questions regarding their pattern of drug use, their motivation for MDMA use and the setting (e.g. clubbing, home with friends), as well as the subjective effects of MDMA. Participants also completed a range of self-report measures of self-reflection and insight, emotional intelligence, and personality, as well as a drug dependency measure. MDMA users displayed higher levels of self-reflection and insight, openness to new experience and lower levels of neuroticism and conscientiousness, in comparison to the control group. The significant predictors of self-reflection and insight were openness, emotional intelligence, MDMA use, extraversion and neuroticism. When the analysis was rerun only for the MDMA group, the significant predictors of self-reflection and insight were openness, emotional intelligence and self-insight effects of MDMA. High levels of self-reported negative effects of MDMA were predictors of a problematic drug use. These findings suggest that there might be a relationship between MDMA use and higher levels of self-reflection and insight; however, longitudinal studies are required to further investigate the causality of this relationship. The results add to existing evidence that MDMA has potential for altering emotional experiences. Further research utilising a prospective design is warranted.
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Anneken, John H. "Glutamate and MDMA Neurobehavioral Toxicity." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342344.
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Cormick, Justin. "Isotope ratio analysis of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethylamphetamine (MDMA) synthesised from helional." Thesis, Griffith University, 2022. http://hdl.handle.net/10072/415810.
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Illicit drug profiling describes the applications of chemical or physical drug profiles to areas such as law enforcement and legislation. Stable isotope analysis by stable isotope ratio mass spectrometry (IRMS) has become a useful tool for illicit drug profiling purposes. The following research was focused on the illicit drug profiling of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxmethylamphetamine (MDMA) by IRMS. Following an extensive literature review, it was surmised that the illicit drug profiling of MDMA (and a lesser extent MDA) by IRMS was complicated. Previous research suggested that stable isotopic compositions of MDA/MDMA may not be characteristic of the synthetic history. Traditional precursors for these drugs have similar, plant-based origins and similar isotopic compositions. The changes to isotopic compositions during the synthesis of MDA/MDMA made it difficult to establish links back to specific precursors. The control of traditional precursors has seen illicit manufacturing utilise alternative compounds. Helional has emerged as a novel precursor for MDA and MDMA, and although recently legislated against in Queensland, Australia, remains largely uncontrolled in many other jurisdictions. The aim of this research was to investigate further the analysis of MDA and MDMA by IRMS, with particular focus on the alternative precursor helional. This was performed with the following individual aims: 1. To investigate the δ2H, δ13C and δ18O composition variation in traditional and alternative MDA/MDMA precursors available in Queensland, Australia including the novel precursor helional. 2. To investigate the δ13C and δ15N composition variation in nitrogen sources used for the synthesis of MDA and MDMA. 3. To investigate the synthesis of MDA and MDMA from helional, and characterisation to determine what, if any isotopic changes occur during each stage of synthesis. 4. To investigate the HCl salt precipitation of MDA and MDMA and to determine what, if any isotopic changes occur during this process. A survey of traditional and alternative precursors and pre-precursors, from which MDA/MDMA can be produced, found a greater variation in stable isotope ratios than previously reported. Of particular interest were samples found with δ13C values more negative than traditional precursors, including helional (between –32.47 and –32.21‰) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) prepared from the methyl-glycidate masking group (methyl-3-[3,4- (methylenedioxy)phenyl]-2-methyl-glycidate (MMDMG)) (–31.39‰). A survey of ATS nitrogen sources by IRMS was also conducted. Much greater variation was found in the δ15N compositions for the alternative nitrogen sources nitromethane (–37.21 to – 0.10‰) and hydroxylamine (–97.87 to +2.19‰). Hydroxylamine is utilised in the production of MDA from helional, and can itself be produced from nitromethane. Changes to stable isotope ratios from precursors and nitrogen sources to MDA and MDMA, and during the HCl salt precipitation, were next investigated. One pathway from helional to MDP2P was investigated via an enamine intermediate, and from MDP2P to MDMA by reductive amination. From helional to MDA two methods were investigated, both proceeding through an amide intermediate. Minimal change was observed in δ13C composition from helional to MDA and MDMA, however, isotopic changes occurred in δ2H, δ15N and δ18O compositions. During the HCl salt precipitation minimal change was seen in δ13C and δ18O composition. When multiple precipitations of the HCl salt were collected, changes occurred to δ2H and δ15N values. If high yields of MDA/MDMA were collected as the HCl salt and homogenised, this isotopic fractionation is expected to be reduced. These results have implications to the illicit drug profiling of MDA and MDMA by IRMS. With minimal changes to δ13C composition, this element may provide limited information about the synthetic history of a sample, especially when MDA or MDMA was prepared from alternative precursors with more negative δ13C values. Changes observed in δ2H, δ15N and δ18O values suggest that these elements may be more useful in characterising batch-to-batch variations between MDA or MDMA samples.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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Bósio, Graziela Costa. "Contribuição individual dos enatiômeros isolados da 3,4-metilenodioximetanfetamina (MDMA) comparativamente com a mistura racêmica no estresse oxidativo hepático, renal e estriatal de ratos." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-19062013-160903/.
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A 3,4-metilenodioximetanfetamina (MDMA, ecstasy), derivada da anfetamina, é uma droga largamente utilizada para fins recreacionais devido à sensação de euforia, energia e desejo de socialização. Apesar de ter a reputação de ser uma droga segura, um número crescente de relatos clínicos e estudos experimentais indica que a MDMA pode produzir toxicidade no SNC, rim, fígado e coração. Embora esteja contida nos comprimidos de ecstasy como racemato (uma mistura de 50% de seus enantiômeros), sua biotransformação é enantioseletiva; em ratos, o enantiômero R é biotransformado mais rapidamente que o S. Como a biotransformação de MDMA é capaz de produzir metabólitos reativos, muito provavelmente, a forma R tenha um maior potencial para gerar ERO/ERN e dano oxidativo nos tecidos do que a forma S. Nos seres humanos ocorre o inverso. Portanto, o presente trabalho teve como objetivo avaliar a contribuição individual de cada enantiômero da MDMA isoladamente, tendo como referência a mistura racêmica, no estresse oxidativo hepático renal e estriatal de ratos. Ratos Wistar machos adultos (180-220g) foram divididos em quatro grupos: controle (salina), MDMA racêmico, R-MDMA e S-MDMA. (2 doses consecutivas de 10 mg/kg no intervalo de 24h, gavage). Parâmetros de estresse oxidativo serão utilizados como a medida da formação de malonaldeído, a determinação de níveis de glutationa reduzida e a atividade da glutationa-S-transferase. Os enantiômeros da MDMA racêmica foram separados por meio da cromatografia em fase líquida de alta eficiência em fase estacionária quiral. Os enantiômeros obtidos mostraram um alto grau de pureza e um bom rendimento. Nossos resultados mostraram que o conteúdo hepático de glutationa total dos ratos do grupo R,S-MDMA e do grupo R-MDMA, foi significativamente menor do que os do controle e os do S-MDMA, revelando que é o enantiômero R que contribui para a depleção de glutationa hepática induzida pela mistura racêmica. A alta reatividade do enantiômero R no fígado também pode ser constatada nos animais tratados apenas com R-MMDA, uma vez que houve uma produção significativamente aumentada de MDA, comparativamente aos outros grupos tratados e o controle. O conteúdo renal de glutationa total foi significantemente menor para todos os grupos tratados quando comparados com o controle. Com relação ao estriado, apenas os animais tratados com o isômero S isoladamente mostraram uma queda significativa da atividade da GST em comparação aos demais grupos tratados e controle. Tomando todos esses dados em conjunto, esse trabalho mostrou que os enantiômeros isolados da MDMA podem atuar de formas distintas no que se refere ao estado redox, principalmente no fígado, uma vez que o isômero R foi o que mais contribuiu para um dano oxidativo.MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine derivate that is largely used for recreational purpose due to its feeling of euphoria, energy and the desire to socialize. Although MDMA has the reputation of being safe, a growing number of clinical reports and experimental studies indicate that MDMA can produce toxicity in the CNS, kidney, liver and heart.Although MDMA is present in ecstasy tablets as a racemate (a 50% mixture of its enantiomer) it has an enantioselective metabolism; in rats, the S-enantiomer is metabolized faster than the R-enantiomer and it is the more active pharmacological form. As the MDMA biotransformation can produce reactive metabolites, probably the R form has a greater potential to generate ROS / ERN and oxidative damage in tissues than the S. In humans, the opposite occurs. Therefore, this aim of the present study was to evaluate the individual contribution of single MDMA enantiomers, compared to racemic mixture in liver, kidney and striatal rats oxidative stress. Adult male Wistar rats (180- 220g) will be divided into four groups: control treatment (saline), racemic MDMA, R-MDMA and S-MDMA (two consecutive doses 24h apart with 10mg/kg, gavage). Oxidative stress status parameters will be used to measure malondialdehyde formation, the reduced glutathione levels determination and the glutathione-S-transferase activity. The enantiomers of racemic MDMA were separated by liquid chromatography high-efficiency chiral stationary phase. The enantiomers showed a high degree of purity and a good recovery. Our results showed that the total glutathione content in liver of rats in R,S-MDMA and R-MDMA group was significantly lower than the control and S-MDMA, revealing that the R-enantiomer that contributes to hepatic glutathione depletion induced by the racemic mixture. The high reactivity of the R enantiomer in the liver can also be observed in animals treated with R-MMDA, since there was a significantly increased production of MDA, compared with other treated and control groups. The total glutathione content in kidney was significantly lower for all treated groups compared with control. With respect to the striatum, only animals treated with the S isomer alone showed a significant decrease in GST activity compared to other treatment and control groups. Taking all these data together, this study shows that the isolated enantiomers of MDMA can act differently with regard to the redox state, mainly in the liver, since the R isomer was the largest contributor to oxidative damage.
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Christian, Michael. "Exploring MDMA and its therapeutic potential." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/672.
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The clinical application of MDMA has long been an issue of great interest for doctors, counselors, researchers, and users alike. Originally synthesized by a pharmaceutical company and subsequently tested on military personnel, the drug was then used by many clinicians and physicians prior to the DEA's strict regulation of the drug, which began in the mid 1980s (Mithoefer et al, 2010). The DEA has classified MDMA a "Schedule 1" drug, which means that it among the most controlled substances, a fact which has hindered the progress of research. For a detailed explanation of the DEA's scheduling of controlled substances, please refer to appendix A. Exception was made to this restriction, however, in 2003 when the US government permitted one organization, the Multidisciplinary Association for Psychedelic Studies ("MAPS," for short), to conduct studies wherein the drug was to be administered to human participants in a clinically controlled experimental environment--a setting which allows for many of the most prevalent confounds found in MDMA research to be minimized and, in some cases, eliminated (Mithoefer et al., 2007; Mithoefer et al, 2010; MAPS.org, 2012). Though MAPS' studies are only just beginning, they have already had promising results in treating protracted cases of PTSD. These recent developments in MDMA research and the results of the subsequent studies have piqued the interest of academics and advocates alike as well as motive numerous other organizations to lend their support to the MAPS organization. This literature review aims to provide an overview of past and present paradigms within the body of MDMA research in order to provide an informational framework within which the recent works regarding the drug's therapeutic merit can be adequately examined.B.S.
Bachelors
Sciences
Psychology
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Bhide, Nirmal S. "Tolerance to MDMA-induced serotonergic neurotoxicity." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1267719790.
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Costa, José Luiz da. "Determinação de 3,4-metilenodioximetanfetamina (MDMA - Ecstasy), 3,4-metilenodioxietilanfetamina (MDEA - Eve) e 3,4-metilenodioxianfetamina (MDA) em fluidos biológicos por cromatografia líquida de alta eficiência: aspecto forense." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-11032005-190039/.
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Em todo o mundo é crescente o uso drogas de abuso sintéticas conhecidas com designer drugs. Os principais representantes desta classe são o Ecstasy ou 3,4-metilenodioximetanfetamina (MDMA) e o Eve ou 3,4-metilenodioxietilanfetamina (MDEA), substâncias com efeitos estimulantes e alucinógenos. No Brasil é crescente sua divulgação pela mídia e o uso recreacional tem sido constatado em vários pacientes que buscam tratamento nas clínicas para dependentes. O presente trabalho constitui validação de metodologia analítica para o diagnóstico laboratorial do uso de MDMA, MDEA e seu produto de biotransformação, o 3,4-metilenodioxianfetamina (MDA), em sangue total e urina, por cromatografia líquida de alta eficiência com detecção por fluorescência. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão, rendimento e capacidade de detectar os analitos mesmos quando presentes em baixas concentrações, o que permite sua aplicação na verificação da intoxicação aguda quanto no uso recreacional destas drogas de abuso.There is a worldwide increase in the use of the synthetic drugs of abuse known as designer drugs. The main representatives of this class are Ecstasy or 3,4-methylenodioxymethamphetamine (MDMA) and Eve or 3,4- methylenodioxyethylamphetamine (MDEA), substances with stimulant and hallucinogenic effects. In Brazil media coverage of them is on the increase and their recreational is in evidence by the growing numbers of patients who seek treatment at drug treatment centers. This paper validates the analytical methodology for the laboratory diagnosis of the use of MDMA, MDEA and their product of biotransformation, 3,4-methylenodioxyamphetamine (MDA), in whole blood and urine by high performance liquid chromatography with fluorescence. The developed methods showed good linearity, precision, accuracy, yield and capacity to detect analytes even when present in low concentrations, which enables its application in cases high intoxication as well as in cases of the recreational use of these drugs of abuse.
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Yubero, Lahoz Samanta 1985. "MDMA pharmacology in humans and serotonergic effects." Doctoral thesis, Universitat Pompeu Fabra, 2013. http://hdl.handle.net/10803/145481.
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3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most abused recreational
drugs in the world. It has been extensively reported that this drug inhibits its own metabolism by
inhibiting a polymorphic liver enzyme, CYP2D6, which is responsible for the clearance of one
quarter of drugs used in therapeutics. This phenomenon has important clinical implications,
since MDMA users display a higher prevalence of psychopathology, particularly of mood
disorders, compared to control population. Importantly, these psychiatric diseases are treated
with drugs most of them substrate of this enzyme. In addition, it is not elucidated how MDMA
is still metabolically cleared even after repeated drug doses. Therefore, the first part of this
thesis was focused on studying the metabolic autoinhibition by MDMA assessing several liver
enzyme activities in men and women.
Although MDMA pharmacology is well established, is it still not clear which is the mechanism
of action of the drug. MDMA interacts with the serotonergic system at several levels, but
nowadays is technically difficult to study the serotonergic function in living human brain.
Imaging methods are limited by a number of factors. Thus, it would be advantageous to have a
reliable peripheral index of the serotonergic activity in the blood. The second part of this thesis
presents the development of several approaches aimed to assess whether the serotonin
transporter in platelets can be used as a peripheral biomarker for central serotonergic activity,
and determine if it plays any role in drug mechanism of action.La 3,4-metilendioximetanfetamina (MDMA, èxtasi) és una de les drogues més consumides al món. Aquesta droga inhibeix el seu propi metabolisme, inhibint un enzim polimòrfic del fetge, el CYP2D6, que és el responsable de l’eliminació d’una quarta part dels medicaments. Aquest fet té implicacions clíniques rellevants, ja que els consumidors de MDMA presenten una prevalença de psicopatologia més alta respecte a la població no consumidora, i moltes de la patologies psiquiàtriques es tracten amb fàrmacs substrats d’aquest enzim. A més, encara no s’ha discernit com aquesta droga pot ser eliminada de l’organisme, inclús després d’haver-ne consumit dosis de manera repetida. Així doncs, la primera part d’aquesta tesi es centra en estudiar l’autoinhibició de la MDMA determinant l’activitat de diferents enzims del fetge, en homes i dones. Encara que la farmacologia de la MDMA està descrita a fons, no està del tot clar quin és el seu mecanisme d’acció. La MDMA interactua amb el sistema serotonèrgic de diverses maneres, però avui en dia és molt difícil estudiar tècnicament el sistema serotonèrgic en el cervell humà. Les tècniques d’imatge estan limitades per molts factors, i per tant, seria molt útil tenir un índex perifèric a la sang de l’activitat serotonèrgica al sistema nerviós central. La segona part d’aquest tesi s’enfoca en el desenvolupament de tècniques per determinar a diferents nivells si el transportador de la serotonina a les plaquetes podria ser un bon biomarcador perifèric de la seva activitat al cervell, i d’aquesta manera veure si el sistema serotonèrgic està implicat en el mecanisme d’acció de la MDMA.
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Lebsanft, Heike Birgit. "MDMA ("Ecstasy") in Tiermodellen des Morbus Parkinson." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972748601.
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ABLE, JESSICA ANN. "MDMA ADMINISTRATION AFFECTS COGNITION IN THE RAT." University of Cincinnati / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1147890602.
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Palhol, Fabien. "Contribution à l'étude des saisies d'Ecstasy par spectrométrie de masse de rapports isotopiques : apport du rapport 15N/14N." Nantes, 2002. http://www.theses.fr/2002NANT2057.
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Illicit drugs have always been used by humans. With scientific progress, new drugs appear each year. At the present time, in France, Ecstasy is the most widespread illicit synthetic drug. The term Ecstasy generally refers to tablets containing 3,4-méthylendioxy-methamphetamine (MDMA). In order to struggle against traffics of drugs of abuse, many methods can be employed. In this study, 13C/12C and 15N/14N ratios of MDMA samples were measured by isotopic techniques, in particular by using a Gas chromatograph-combustion-isotope ratio mass spectrometer (GC-C-IRMS). The aim of such analyses was to confirm that links exists between precursors, synthetic pathways and MDMA, and in the same way to establish links between drug seizures. . .
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Turner, Alexandra. "What is the difference between Ecstasy and MDMA?" Thesis, Anglia Ruskin University, 2016. http://arro.anglia.ac.uk/701011/.
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In society there is a discrepancy that has developed in what the public understands about what Ecstasy is, in relation to the term ‘MDMA’. MDMA, the abbreviation for 3, 4-methylenedioxymethamphetamine, is the chemical constituent that has most commonly been associated with the street drug known as Ecstasy. Though the use of Ecstasy was reportedly on the decrease, a new product has emerged known as crystal or MDMA powder. This is alongside new competing compounds entering the market, most notably Mephedrone. The research examined explores the changing perception around what the terms Ecstasy and MDMA represent, comparing their popularity and prevalence with that of Mephedrone. This was investigated using an interdisciplinary approach, utilizing methods drawn from social sciences and analytical chemistry. Two online social research surveys were employed to establish what the public knew and understood about the terms, Ecstasy and MDMA and the drug Mephedrone. The surveys included both quantitative questions regarding specific drug knowledge and qualitative questions which asked participants about their reasons behind selecting to use a substance. The surveys provided a social context and highlighted specific perceptions that were held about these drugs. The results from the surveys were compared to seizure data collected from the Cambridgeshire Constabulary, which provided a timeline of the emergence and prevalence of the types of Ecstasy/MDMA and Mephedrone being seized. The perceptions were also compared to a qualitative chemical analysis of seized samples using Gas Chromatography – Mass Spectrometry (GC-MS). In the findings from this research there is a definite gap between what the public know and perceive about the terms Ecstasy, MDMA and Mephedrone. A key finding from this research is what is reportedly known about Ecstasy has not translated into what is known about MDMA. There is an observed disassociation between these two terms. Mephedrone, on the other hand appears to have fallen into obscurity post its media high of 2010. The responses to the social surveys indicate a clear preference for MDMA over ‘Ecstasy’ or Mephedrone, as the former is seen as being of better ‘quality’. The user preference was supported by the findings from the seiuzers recorded in Cambridge, with the new crystal form being the most dominant type seized post 2012 and Mephedrone seizures declining after its control in 2010. In reporting the purity of street samples, the public perception was again supported as the crystal materials contained a higher percentage of the chemical MDMA. This is the first reported study of the relative purity of the alternate forms of MDMA.
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Turner, Alexandra. "What is the difference between Ecstasy and MDMA?" Thesis, Anglia Ruskin University, 2016. https://arro.anglia.ac.uk/id/eprint/701011/1/Alexandra_Turner_Thesis_03.03.2016.pdf.
Full textAbstract:
In society there is a discrepancy that has developed in what the public understands about what Ecstasy is, in relation to the term ‘MDMA’. MDMA, the abbreviation for 3, 4-methylenedioxymethamphetamine, is the chemical constituent that has most commonly been associated with the street drug known as Ecstasy. Though the use of Ecstasy was reportedly on the decrease, a new product has emerged known as crystal or MDMA powder. This is alongside new competing compounds entering the market, most notably Mephedrone.
The research examined explores the changing perception around what the terms Ecstasy and MDMA represent, comparing their popularity and prevalence with that of Mephedrone. This was investigated using an interdisciplinary approach, utilizing methods drawn from social sciences and analytical chemistry. Two online social research surveys were employed to establish what the public knew and understood about the terms, Ecstasy and MDMA and the drug Mephedrone. The surveys included both quantitative questions regarding specific drug knowledge and qualitative questions which asked participants about their reasons behind selecting to use a substance. The surveys provided a social context and highlighted specific perceptions that were held about these drugs. The results from the surveys were compared to seizure data collected from the Cambridgeshire Constabulary, which provided a timeline of the emergence and prevalence of the types of Ecstasy/MDMA and Mephedrone being seized. The perceptions were also compared to a qualitative chemical analysis of seized samples using Gas Chromatography – Mass Spectrometry (GC-MS).
In the findings from this research there is a definite gap between what the public know and perceive about the terms Ecstasy, MDMA and Mephedrone. A key finding from this research is what is reportedly known about Ecstasy has not translated into what is known about MDMA. There is an observed disassociation between these two terms. Mephedrone, on the other hand appears to have fallen into obscurity post its media high of 2010. The responses to the social surveys indicate a clear preference for MDMA over ‘Ecstasy’ or Mephedrone, as the former is seen as being of better ‘quality’. The user preference was supported by the findings from the seiuzers recorded in Cambridge, with the new crystal form being the most dominant type seized post 2012 and Mephedrone seizures declining after its control in 2010. In reporting the purity of street samples, the public perception was again supported as the crystal materials contained a higher percentage of the chemical MDMA. This is the first reported study of the relative purity of the alternate forms of MDMA.
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Huff, Courtney L. M. S. "MDMA and Glutamate: Implications for Hippocampal GABAergic Neurotoxicity." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444662.
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Ben, Hamida Sami. "Interactions entre MDMA et éthanol : effets comportementaux, physiologiques et pharmacologiques." Strasbourg, 2009. http://www.theses.fr/2009STRA6036.
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Des expériences réalisées dans notre laboratoire sur des rats mâles de la souche Long-Evans, ont montré que l’éthanol, administré en même temps que la 3,4- méthylènedioxymethamphétamine (MDMA ; ecstasy), atténue l'hyperthermie et potentialise les effets locomoteurs induits par cette drogue. Ce travail de thèse s’inscrit dans la continuité de ces observations. Ma démarche expérimentale a consisté en une étude fondamentale, dont l’objectif était de mieux comprendre les interactions pharmacocinétiques et pharmacodynamiques entre la MDMA et l’éthanol. Nous avons montré l’aspect unique de l’interaction entre ces deux drogues par rapport aux interactions entre l’éthanol et la cocaïne ou l’amphétamine. De plus, nous avons démontré que les effets protecteurs de l’éthanol face aux effets hyperthermiants de la MDMA dépendent du régime d’administration et de la température ambiante. Par ailleurs, à l’aide d’une approche pharmacologique, complétées par des expériences en neuroimagerie fonctionnelle, nous avons mis en évidence l’importance de la composante dopaminergique au niveau du noyau accumbens dans les effets psychostimulants de la MDMA+EtOH. En effet, la présence d’éthanol en plus de la MDMA semble impliquer la libération de dopamine dans cette structure. Cette hypothèse pourrait expliquer l’augmentation des effets appétitifs de la MDMA en cas de co-administration avec de l’éthanolEcstasy is commonly used in combination with other drugs, and particularly with alcohol (ethanol). Previous studies performed in the laboratory have shown in Long- Evans rats that ethanol (EtOH) potentiated 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperlocomotion, while protecting against its hyperthermic effects. The present work, in continuation of these observations, provided a fundamental understanding of the pharmacokinetic and pharmacodynamic interactions between MDMA and ethanol. For this purpose, we used physiological, behaviour and pharmacological approaches, complemented by functional neuroimaging studies. We showed that the effects of the interaction between MDMA and ethanol were different from those of the interaction between EtOH and amphetamine or cocaine. We also showed that the effects of ethanol on MDMA-induced hyperthermia were dependent on ambient temperature and on MDMA administration conditions. Finally, we demonstrated that dopamine transmission in the nucleus accumbens was involved in psychomotor action of the combination of MDMA and ethanol. It is probable that MDMA-induced dopamine release within the nucleus accumbens is probably increased by co-administration of ethanol, and this increase might explain the reinforcing effect of the combination of MDMA and ethanol
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Fonsart, Julien. "Toxicité aiguë, métabolisme et pharmacocinétique de la 3,4-méthylènedioxyméthamphétamine (MDMA, ecstasy) : influence du sexe chez le rat Sprague-Dawley." Paris 5, 2008. http://www.theses.fr/2008PA05P651.
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La consommation de 3,4-méthylènedioxyméthamphétamine (MDMA, ecstasy), amphétamine synthétique provoquant une hyperthermie et un syndrome sérotoninergique mortels, s'est considérablement accrue. Les hommes semblent plus sensibles à sa toxicité aiguë et ses effets secondaires physiologiques que les femmes (sex-ratio de 4:1). Plusieurs études ont rapporté des constatations similaires chez le rongeur. La présenté étude montre une différence de DL50 marquée chez les rats mâles et femelles (18 contre 42,5 mg/kg), mais aussi d'effet hyperthermique (0,9°C) de la MDMA, tout en évaluant l'hypothèse d'une différence métabolique ayant des répercussions sur la pharmacocinétique de la molécule. La N-déméthylation de la MDMA en MDA, métabolite plus actif et toxique, est 3,3 fois plus importante in vitro sur microsomes hépatiques de rats mâles, conséquence d'une activité double du CYP1A2 hépatique la catalysant principalement. Cette différence métabolique conduit à des profils pharmacocinétiques différents entre mâles et femelles pour la MDMA comme ses métabolites, évalués par une technique de CLHP/SM permettant une quantification simultanée de la MDMA et de ses principaux métabolites. Ainsi les concentrations plasmatiques de MDA sont plus élevées chez les mâles après administration sous-cutanée ou intraveineuse de MDMA, du fait d'un métabolisme plus important de la MDMA que de la MDA, conduisant à une exposition systémique plus longue, qui expliquerait la différence de mortalité observée, les DL50 de la MDA ne présentant pas de différence liée au sexe. Ces résultats suggèrent que les différences métaboliques sont capitales dans la toxicité des amphétaminiques, et surtout de la MDMAUse of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), an illicit designer drug that can lead to life-threatening hyperthermia and serotonin syndrome, has greatly increased over the last years. Men appear to be more sensitive to acute toxicity than are women, with a 4:1 sex-ratio of lethality, and so to its physiological adverse effects. Some studies also reported similar phenomenon in rodents. The present study demonstrates sex-difference in LD50 (18 vs. 42. 5 mg/kg) and hyperthermic effect (0. 9°C) of MDMA in Sprague-Dawley rats, also evaluating metabolic differences between sexes affecting pharmacokinetics of the drug. N-demethylation of MDMA to MDA, a more active and toxic metabolite, is 3. 3-fold more important in vitro using male rats hepatic microsomes, while CYP1A2 catalysing the reaction is twice more active compared to females. Such metabolic discrepancy modifies in a sex-dependent manner the pharmacokinetics of MDMA and its metabolites, which have been evaluated using a liquid chromatography-mass spectrometry method specially designed for the present study and allowing simultaneous quantification of MDMA and its main metabolites. MDA plasma levels appear to be higher in males, whatever the route of administration (subcutaneous or intravenous) of MDMA, caused by a higher metabolism of MDMA than of MDA, and leading to a longer systemic exposure of males rats. Such differences could explain observed sex-difference in lethality, as LD50 of MDA did not differ between sexes. The data suggest that the metabolic differences in amphetamine-related drugs are of major importance for their toxicity, and especially for MDMA
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Medina, Krista Lisdahl. "Ecstasy (MDMA) Exposure and Neuropsychological Functioning: A Polydrug Perspective." Cincinnati, Ohio : University of Cincinnati, 2005. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1112218607.
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Orejarena, Maria Juliana. "Neurobiological mechanisms involved in MDMA-Seeking behaviour and relapse." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7229.
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(+) 3,4-metilendioximetanfetamina (MDMA), popularmente conocida como "éxtasis", es una droga susceptible de producir adicción en algunos individuos. Actualmente es consumida principalmente por adolescentes y jóvenes. Los particulares efectos psicoactivos inducidos por la MDMA, permiten distinguirlo de manera clara de otros psicoestimulantes o compuestos alucinógenos. Esta droga actúa principalmente activando el sistema dopaminérgico y serotonérgico en los circuitos neurales de placer. Sin embargo, los mecanismos neurobiológicos implicados en las propiedades adictivas de esta droga no han sido aún esclarecidos. El trabajo presentado en esta Tesis Doctoral ha puesto de manifiesto algunos aspectos claves de estos procesos que eran desconocidos hasta el momento. Hemos encontrado que el receptor de serotonina 5-HT 2A participa de forma critica en las propiedades reforzantes de la MDMA, contrario a lo observado en el caso de otros psicoestimulantes. Además, el bloqueo farmacológico de este receptor puede prevenir la reinstauración de la búsqueda de la MDMA, desencadenada por un estímulo o clave previamente asociado a su consumo. Estos efectos pueden ser debidos al bloqueo del control excitatorio que normalmente ejercen estos receptores sobre los niveles de dopamina en estructuras mesolímbicas, como ha sido revelado en nuestros estudios de microdiálisis. Hemos demostrado también que la MDMA puede actuar como clave interoceptiva y desencadenar la recaída a la búsqueda y consumo de cocaína. Adicionalmente, nuestros estudios han mostrado que tanto la activación del sistema dopaminérgico mesolímbico, como los cambios en la expresión génica en diferentes ´areas cerebrales que ocurren tras la administración de la MDMA, dependen de si el sujeto participa de manera activa en el consumo de esta droga, o si por el contrario la recibe de forma pasiva. En conclusión, este trabajo resalta la importancia de los procesos de aprendizaje y memoria sobre las propiedades reforzantes/recompensantes de la MDMA. Además, nuestras investigaciones aportan nuevas evidencias en relación a la participación del sistema serotonérgico en la búsqueda y recaída al consumo de esta droga.(+) 3,4-methylenedioxymethamphetamine (MDMA), commonly known as "ecstasy", is currently a highly consumed drug with liability to produce addiction in some individuals. MDMA induces unique psychoactive effects that clearly distinguish it from hallucinogenic or psychostimulant drugs. MDMA mainly enhances the activity of both the serotonergic and the dopaminergic system in the esolimbic brain reward pathways. However, the neurobiological mechanisms underlying its possible addictive properties are still not fully understood. In the present work, we have contributed to this subject by establishing that the serotonin 5-HT2A receptor, in contrast to what has been observed for other drugs of abuse, is critical for MDMA-induced reinforcement. Moreover, the pharmacological blockade of this receptor can prevent cue-induced relapse. This effect is possibly mediated by its excitatory control over basal and MDMA-induced increase in midbrain dopamine, as supported by our microdialysis data. Furthermore, we have also shown that MDMA can act as an interoceptive cue to induce relapse to cocaine-seeking behaviour. Additionally, we demonstrated differential changes at the level of the dopaminergic brain reward pathway and gene expression changes in different brain areas, following self-administeredMDMAin comparison to passive administration. These results underpin the impact of a learning component in the rewarding/reinforcing properties of MDMA, and provide new evidence for the serotonergic involvement in MDMA-seeking behavior and relapse.
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Kuypers, Kim Paula Colette. "Psychedelic bliss: memory and risk taking during MDMA intoxication." [Maastricht : Maastricht : Universiteit Maastricht ] ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=8303.
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Straiko, Megan M. W. "Consequences of ± 3,4-methylenedioxymethamphetamine (MDMA) administration in the rat." Cincinnati, Ohio : University of Cincinnati, 2006. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1153777964.
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Thesis (Ph. D.)--University of Cincinnati, 2006.Title from electronic thesis title page (viewed Sept. 11, 2007). Includes abstract. Keywords: MDMA; neurotoxicity; C-tau; sex behavior; nitric oxide. Includes bibliographical references.
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Rodsiri, Ratchanee. "MDMA : binge use and functional outcomes in the rat." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/13386/.
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3,4-Methylenedioxymethamphetamine (MDMA) use has increased dramatically and more intensive patterns of use such as binging have become common. This thesis pays particular attention to the translation of animal data to humans by examining low doses and binge type repeated regimen of MDMA in the rat. The functional effects especially acute and long-term effects on memory have been investigated together with the measurement of changes in 5-HT and dopamine to investigate the possible link of these neurotransmitters and the functional effects of MDMA. The acute effect of single low doses of MDMA on memory was initially examined and it was shown that MDMA (3 mg/kg) acutely disrupted novel object discrimination when given 30 min before the test. However there was no change in 5-HT and dopamine in the hippocampus, striatum and frontal cortex 150 min after MDMA administration. The combined techniques of radiotelemetry and in vivo microdialysis were used to examine effects of 'binge-type' repeated low dose MDMA administration (3 or 6 mglkg i.p. x 3 every 2 h). Locomotor activity, body temperature and 5-HT release in the hippocampus were simultaneously measured in the same animal during MDMA administration. MDMA (3 x 6 mglkg) increased locomotor activity after each injection. In addition MDMA (3 x 3 mg/kg) produced hypothermia following each injection while MDMA (3 x 6 mg/kg) changed thermoregulation as it decreased body temperature after the first injection and then increased body temperature after the second to a maximum of + 1.3 °C after the third injection. Both 'binge' doses of MDMA however increased extracellular 5-HT in the hippocampus after each injection and there was no correlation between 5-HT release in the hippocampus and changes either in locomotor activity or body temperature. The long-term effect of repeated administration of low doses of MDMA (3 or 6 mg/kg i.p. x 3 every 2 h) on memory was investigated using novel object discrimination 2 weeks after treatment. To imitate the single housing condition used in radiotelemetry experiments, rats were individually housed during drug treatment. MDMA (3 x 6 mglkg) caused impairment of novel object discrimination but there was no change in 5-HT, dopamine and their metabolites in the hippocampus, striatum and frontal cortex 2 weeks after MDMA treatment suggesting no contribution of either 5-HT or dopamine loss to the MDMA-induced memory impairment. The effects of housing conditions on MDMA-induced changes in body temperature and subsequent 5-HT neurotoxicity were determined. Group housed rats showed a similar pattern of changes in body temperature to singly housed rats measured by radiotelemetry following MDMA (3 x 6 mg/kg) suggesting no effect of the housing condition on MDMA-induced changes in body temperature. MDMA (3 x 6 mg/kg) given to group housed rats however produced loss of hippocampal 5-HT 2 weeks after treatment indicating that MDMA-induced hyperthermia is not an essential factor for MDMA-induced neurotoxicity. The influence of tyrosine on MDMA-induced 5-HT neurotoxicity was determined by depletion of brain tyrosine availability by giving a tyrosine-free amino acid mixture (1 glkg twice 1 h apart) to Dark Agouti rats before and after MDMA administration (12.5 mglkg i.p.). A small increase of tyrosine in the hippocampus and striatum occurred in rats treated with MDMA alone. Although the tyrosine-free amino acid mixture decreased tyrosine in the hippocampus and striatum by more than 50% 2 h after administration, this did not protect against MDMA-induced acute hippocampal and striatal 5-HT depletion and long-term 5-HT loss in the hippocampus indicating no effect of tyrosine on MDMA-induced 5-HT neurotoxicity. Overall the results of the present study provide extensive evidence for acute and long-term memory impairments following single and 'binge-type' repeated low dose MDMA administration and that these effects may translate effectively to human conditions. The memory impairments appeared to have no link with 5-HT and dopamine thus it is important to focus on other factors involved in the mechanism of MDMA-induced memory impairments.
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Easton, Neil. "3,4-Methylenedioxymethamphetamine (MDMA, Ecstacy) neurotoxicity : role of thioether adducts." Thesis, Nottingham Trent University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272853.
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Sharifimonfared, Ghazaleh. "Pathways through MDMA use : a qualitative life story study." Thesis, University of Hull, 2016. http://hydra.hull.ac.uk/resources/hull:15621.
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MDMA is a popular psychoactive drug that is highly associated with raves and clubbing culture. Consumers experience feelings of euphoria, joy, and confidence. Despite the considerable research on MDMA, non-problematic aspects of use remain under researched. The aim of this study was to understand MDMA use and pathways into and out of consumption. More specifically, the research examines the experience of ex-heavy MDMA users through their MDMA journeys. This qualitative study employed an online questionnaire inspired by the Life Story Approach. Participants were recruited using ethnographic research methods and through related online forums. The inclusion criterion was individuals who self-identified as ex-heavy MDMA users, who have now cut down or completely stopped MDMA use. 104 former heavy MDMA users were surveyed. Data was analysed thematically from which six main categories were identified: Journey; Polydrug use; Role of drugs during consumption; Changes in drug use pattern; Changes in life; and Advice. A common positive tone runs through all the themes, and most reported negativity is due to drug use as a whole. Data analysis highlighted Harm reduction and Function and pleasure enhancement as important overarching themes for participants. MDMA was generally used in specific settings to enhance an event or experience, such as music related events. But MDMA also enhanced intimacy, social bonding, meditation, and was used by some as a cognitive enhancer and therapeutic aid helping to think and feel differently. Many described positive psychological and social effects of use that remained after MDMA use, and often lasted permanently. Although a stop or a cut-down in MDMA use is often a natural process, it could still be cut-down or stopped actively by making lifestyle changes such as distancing oneself from the associated scenes and people. The results of this study bring a foundation of understanding MDMA use and pathways into and out of frequent use, which could particularly be useful in designing appropriate harm reduction programs and inform policy making. Likewise, present findings could help to address further aspects of MDMA use and non-problematic drug use in general.
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Wareing, M. "Working memory and executive deficits among MDMA (Ecstasy) users." Thesis, Edge Hill University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439660.
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Roberts, C. A. "Neurophysiological correlates of ecstasy/MDMA use on executive functioning." Thesis, Liverpool John Moores University, 2014. http://researchonline.ljmu.ac.uk/4524/.
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The purpose of this thesis was to assess the integrity of the serotonin system, by measuring the neurophysiological response to tasks that measure executive functions, and neuroendocrine function in ecstasy users and non-users. Each of the proposed executive functions outlined in Miyake et al.’s (2000) conceptual framework (inhibition, switching and updating) as well as the addition of access to semantic/long term memory made by Fisk and Sharp (2004), was assessed using behavioural tasks in combination with EEG and fNIRS. Behavioural performance between ecstasy users and various controls (polydrug and drug naive) was equivalent throughout the thesis. However ERP analysis revealed ecstasy-related atypicalities in cognitive processing during inhibitory control, switching and access. Ecstasy users displayed increases in P2 and N2 components during these tasks that reflect recruitment of additional resources. A diminished P3 response during the switching task was evident for ecstasy users and polydrug users relative to controls. Regression analyses suggest that lifetime cannabis use may be an important factor for this function. Results from fNIRS suggest that ecstasy users show an increased haemodynamic response during all four executive functions relative to non-users, which suggests that ecstasy users are engaged in more effortful cognition than controls. Increases in neuronal activation whilst performing at a similar level behaviourally are understood as recruitment of additional resources. Again during switching cannabis use may have been an important factor. Another aim of this thesis was to assess neuroendocrine function. Ecstasy users displayed elevated basal cortisol levels relative to polydrug controls and drug naive controls. The results suggest that ecstasy is detrimental to the integrity of the HPA-axis. This thesis provides support for ecstasy-related damage to the serotonergic system and should be used in educating prospective ecstasy users of relative harms.
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Hatala, Elaine M. "Characteristics and Predictors of Ecstasy (MDMA) Use During College." Diss., Temple University Libraries, 2008. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/882.
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Public HealthPh.D.
This cross-sectional investigation examined characteristics of ecstasy use during college and associations between ecstasy use during college and demographic factors, family functioning, mental health, and stage of change for ecstasy use. In addition a multivariate model was developed to predict characteristics of ecstasy use during college. An electronic survey was sent to all undergraduate students enrolled at a large urban university in the mid-Atlantic region of the United States during the spring of 2007. Demographic factors and characteristics of ecstasy use were examined using standardized measures employed in national drug use surveys and by the World Health Organization. Measures associated specifically with ecstasy use during college were developed for this investigation. Family functioning was measured with the Parent Adolescent Communication Scale. Mental health was measured with the K6 screening instrument for nonspecific psychological distress. Stage of change was measured with a five-stage algorithm. The final sample for analysis consisted of 194 participants who reported ecstasy use during college and 2849 participants who reported no ecstasy use during college. Data were described using conventional descriptive statistics, chi-square statistics and non-parametric statistics. A logistic regression model was used to identify variables associated with ecstasy use during college. Based on the results, the following generalized conclusions were drawn: ecstasy continues to be used by college students at large urban universities in the mid-Atlantic region of the United States; because the majority of college students reported using ecstasy for the first time during college and also reported using ecstasy for up to two years, it appears that the college environment is a contextual factor for ecstasy use; lower family communication is associated with ecstasy use during college; psychological distress is associated with ecstasy use during college; being white (versus non-white), male (versus female) and having low or moderate (versus high) family communication each is independently associated with ecstasy use during college; differences in stage of change for ecstasy use among ecstasy users and the demographic profile of ecstasy users compared to non-ecstasy users suggest that prevention, education and intervention efforts should be designed to match the unique factors associated with ecstasy use during college.
Temple University--Theses
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Gabay, Anthony Stuart. "An investigation of social cognition using psilocybin and MDMA." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/an-investigation-of-social-cognition-using-psilocybin-and-mdma(dedc1c2c-5023-4cba-9994-6178214334f3).html.
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Impairments of social function are increasingly thought to be fundamental to the psychopathology of psychiatric disorders. Current treatments are not assessed against these social domains and the effects of medication are poorly understood. Furthermore, the neural mechanisms and psychopharmacology underlying these functions in the healthy population are poorly understood. This thesis addresses this knowledge gap. A meta-analysis of antipsychotic treatment effects on emotion processing in schizophrenia confirms the lack of efficacy of current treatments in treating these social deficits. Following this, the thesis largely focuses on social decision-making, investigating tasks which model trust, cooperation and social norm violations. A meta-analysis of neuroimaging studies investigating the Ultimatum Game (UG) provides robust evidence of regions underlying the processing of social norms. Results are presented from two psychopharmacological studies, utilising serotonergic agonists to investigate their effects on social decision-making and emotion processing. The first study administered psilocybin with an open-label design. This study additionally investigated the efficacy of a src-kinase inhibitor to attenuate any psilocybin effect; this followed a placebo-controlled, double-blind design. The second study investigated 3,4-methylenedioxymethamphetamine (MDMA) with a placebo-controlled, double-blind design. Both MDMA and psilocybin caused a decrease in rejection of unfair offers in the UG. MDMA increased cooperation with trustworthy, but not untrustworthy, partners in an iterated Prisoner’s Dilemma (PD), as well as reducing recognition of negative facial affect. Increased cooperation in the PD was accompanied by increased activation in the superior temporal sulcus, cingulate cortex and insula, during feedback of other player’s decisions. The findings of these studies suggest that serotonergic mechanisms are fundamental to the processing of normative behaviour during interpersonal interactions. Manipulation of this neurotransmitter system produced context-sensitive changes in behaviour. These behavioural alterations were accompanied by changes in activity of brain regions proposed to be involved in the processing and appraisal of other’s intentions and motivations. It is hypothesised that this was largely achieved through activity at the serotonin 2A receptor. These findings provide insight for the development of new treatment mechanisms for disorders of social cognition.
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Almeida, Stella Pereira de. "Primeiro perfil do usuário de "êxtase" (MDMA) em São Paulo." Universidade de São Paulo, 2000. http://www.teses.usp.br/teses/disponiveis/47/47132/tde-17012006-152155/.
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O presente estudo teve como objetivo identificar os padrões de uso de "êxtase" na cidade de São Paulo. Os usuários foram recrutados através da técnica de amostragem snowball, também utilizada para o recrutamento do grupo controle, composto de indivíduos com estilo de vida semelhante aos primeiros mas que nunca haviam experimentado "êxtase" (não usuários). Usuários (52) e não usuários (52) foram entrevistados quanto às características sócio-demográficas e quanto ao uso de drogas psicotrópicas; usuários também responderam questões sobre circunstâncias de uso e efeitos do "êxtase". Através da Escala de Impulsividade de Barratt e dos Inventários de Depressão de Beck e de Ansiedade Traço-Estado (IDATE-traço) foram medidas impulsividade, depressão e ansiedade de ambos os grupos. Os dois grupos apresentaram características sócio-demográficas semelhantes: a maioria pertencia à classe média, era jovem, heterossexual, solteira e com nível superior. Entre os usuários o consumo de outras drogas psicotrópicas foi expressivamente superior. Outras características mais freqüentes no grupo de usuários foram a presença de tatuagens e piercings, a frequência a "raves" e a preferência pela música eletrônica. No Inventário de Depressão de Beck os usuários apresentaram pontuação significativamente menor quanto à depressão. Os resultados das escalas de impulsividade e ansiedade não apresentaram diferenças significativas entre os dois grupos. Os padrões de uso de "êxtase" dos usuários entrevistados são semelhantes aos padrões descritos por pesquisas realizadas na Europa e em Sidney: a maioria dos usuários consome um ou dois comprimidos a cada episódio de uso, apenas nos finais de semana ou férias, mais freqüentemente na companhia de várias pessoas, em ambientes ligados ao lazer noturno, como lugares para dançar, "raves" e festas. Os comprimidos são geralmente adquiridos de amigos ou conhecidos nesses locais. A maioria dos usuários associa "êxtase" a outras drogas psicotrópicas, particularmente maconha. As características sócio-demográficas dos usuários entrevistados e seus padrões de aquisição e consumo de "êxtase" indicam um caráter pouco marginal do uso. São sugeridas estratégias de Redução de Dano caso o uso de "êxtase" se difunda em São Paulo.The present study was aimed at identifying patterns of ecstasy (MDMA) use in the city of São Paulo. Ecstasy users were recruited through the snowball technique. Using the same technique, a control group of subjects that had never tried the drug (non users) was recruited among individuals sharing with users a similar life style. Users (N=52) and non users (N=52) were interviewed in order to obtain socio-demographic data and data on use of psychoactive drugs; users were also questionned as to the circumstances surrounding their use of the drug. Besides, levels of anxiety, depression and impulsiveness were assessed through Spielberger's IDATE Trace Inventory, Beck's Depression Inventory and Barratt Impulsiveness Scale. Both users and non users revealed similar socio-demographic characteristics: most subjects were middle class young heterosexual single men and women who had a college degree. Multiple drug use was more frequent among users than among non users. Other features that were significantly more accentuated among users than among non users were the presence of tattoos and piercings, the frequency to raves and the preference for electronic music. Beck Inventory results pointed to significantly lower depression scores among users. No differences were observed between groups in anxiety and impulsiveness scores. Ecstasy consumption patterns among users are similar to those reported in Europe and Australia: most subjects take one or two pills per episode, during weekends or vacations, usually with company and in social gatherings such as dancings, raves and parties. The drug is predominantly acquired from friends or acquaintances in these same spots. Most users reported consuming ecstasy in combination with other psychoactive drugs, particularly marihuana. The socio-demographic features of users as well as the way they buy and consume the drug suggest that the present pattern of use is not connected to illegal or marginal activities. Harm reduction strategies are suggested in case of ecstasy's use increases and spreads among the young population of the city.
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Agostinho, Túlio de Castro. "Análise voltamétrica de 3,4-metilenodioximetanfetamina." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/59/59138/tde-12122012-102825/.
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O propósito do estudo realizado foi de investigar o comportamento voltamétrico da 3,4-metilenodioximetanfetamina (MDMA), substância psicoativa do ecstasy, uma droga que tem se tornado cada vez mais popular entre os usuários de drogas. Empregou-se o uso da técnica de cromatografia líquida de alta eficiência, para isolar a substância a partir de amostras de ecstasy obtidas em parceria com a Polícia Científica de Ribeirão Preto, bem como a técnica de espectrometria de massas, para confirmar a presença da MDMA nas mesmas. Os estudos voltamétricos foram realizados utilizando-se um sistema de três eletrodos, sendo o eletrodo de trabalho de carbono vítreo, eletrodo de referência Ag/AgCl e eletrodo auxiliar de fio de platina. O comportamento eletroquímico desta substância foi investigado diante de diferentes modalidades voltamétricas: Voltametria cíclica, de pulso diferencial e de onda quadrada, nas quais se pôde observar um pico anódico em Ep = +1,1 V. Foram otimizados os parâmetros voltamétricos de modo a tornar a análise mais rápida e sensível, sem perda de intensidade e qualidade do sinal voltamétrico. Com os parâmetros voltamétricos otimizados, foram construídas curvas analíticas para o analito em questão nas diferentes modalidades voltamétricas estudadas. Foi possível determinar o teor de MDMA nas cinco diferentes amostras de ecstasy utilizadas, das quais quatro apresentaram MDMA com teores variando de 3 a 10% (m/m) e uma na qual não foi constatada a presença da droga, mas sim de outro fármaco, a lidocaína.The main purpose of the present study was to investigate the voltammetric behavior of 3,4-methylenedioxymethanphetamine (MDMA), the psychoactive substance of ecstasy, a drug that has become increasingly popular among drug users. The high performance liquid chromatography technique was employed in order to isolate the substance from ecstasy samples obtained in partnership with Polícia Científica de Ribeirão Preto and also the mass spectrometry technique was employed to confirm the presence of MDMA. The voltammetric studies were performed using the three electrodes system, being glassy carbon as the working electrode, Ag/AgCl as the reference electrode and platinum wire as counter electrode. The electrochemical behavior of the substance was investigated using different voltammetric techniques: Cyclic, differential pulse and square wave voltammetry modalities, in which an anodic peak was observed at Ep = +1,1 V. The voltammetric parameters were optimized in order to make the analysis faster and more sensitive, without loss of quality and intensity of the voltammetric signal. With the voltammetric parameters optimized, analytical curves of the studied analyte were built for the different voltammetric techniques. It was possible to determine the content of MDMA in the five different ecstasy samples utilized, in which four showed MDMA with contents ranging from 3 to 10% (m/m) and one in which no MDMA was observed but another drug, lidocaine.
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Fallon, John Kevin. "Stereospecific analysis and enantiomeric disposition of 3,4-methylenedioxymethamphetamine (MDMA) in man." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313776.
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Leão, Anabela Pereira. "Lesões musculares esqueléticas induzidas pela MDMA (‘Ecstasy’) e pelo exercício físico." Master's thesis, Universidade de Aveiro, 2003. http://hdl.handle.net/10773/18837.
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Mestrado em Métodos Biomoleculares AvançadosCom este trabalho procurou-se estudar, no músculo soleus de ratinho, os efeitos da administração da MDMA e da sua associação com o exercício físico. Para isso utilizaram-se 72 ratinhos Charles River CD1, distribuídos ao acaso por quatro grupos experimentais (n=18/grupo), que foram sujeitos à administração intraperitoneal de soro fisiológico e/ou 3,4- metilenodioxometanfetamina (MDMA) na dose de 10 mg/Kg. Destes grupos organizaram-se subgrupos (n=6), dos quais alguns foram submetidos ao exercício físico em tapete rolante, no plano horizontal, durante 90 minutos, a 75% da velocidade máxima dos animais Procedeu-se à avaliação de diferentes parâmetros, metabólico (temperatura subcutânea), bioquímico plasmático (creatina cínase-CK) e bioquímicos musculares (mieloperoxidase–MPO e Nacetil ?-glucosaminidase–NAG), em diferentes momentos de avaliação (0, 24 e 48 horas após a administração intraperitoneal de solução salina e/ou MDMA). Todo o protocolo experimental foi acompanhado pela avaliação morfológica do tecido muscular esquelético à luz da microscopia óptica e electrónica, quantificando-se as fibras lesadas (alteração do padrão estriado, vacuolização sarcoplasmática, necrose segmentar e núcleos em posição central). Neste contexto verificou-se que a CK plasmática apresentava o pico de actividade enzimática imediatamente após o exercício para todos os grupos experimentais. Constatou-se ainda que a MDMA produziu um efeito hipertérmico significativo nos animais, não se verificando qualquer influência do exercício físico. A análise morfológica demonstrou que a acção exercida pela MDMA originou, uma lesão muscular extensa expressa pelo número de fibras lesadas. Averiguou-se ainda que esta droga de abuso causa um infiltrado essencialmente linfocitário, verificando-se o pico às 24 horas após o exercício, sendo progressivamente substituído por neutrófilos e/ou macrófagos, como indiciam os valores da MPO e NAG. Pode-se concluir que a MDMA possui um efeito tóxico sobre as fibras musculares e que se prolongam por mais tempo para o grupo que foi sujeito em simultâneo ao exercício físico, o que pronuncia um fenómeno lesivo mais intenso.
This work presents the in vivo performed study for the evaluation of MDMA’s skeletal muscle toxicity, in an attempt to contribute for the understanding of the possible mechanisms involved in this effect. For this purpose were used 72 Charles River CD-1 mice (30-40g), randomly distributed by 4 groups (n=18 mice/group), and submitted to an i.p. injection of 0,1 mL of sterile saline and 10mg/Kg of 3,4-methylenedioxymethamphetamine (MDMA), using sterile saline as vehicle. Some of these groups were subjected to a treadmill level run at 75% of the maximal speed of these mice, during 90 minutes. Immediately before sacrifice 1 mL of blood was collected from inferior vena cava of all animals to quantify plasma creatine kinase activity as an indirect marker of skeletal muscle injury. Both soleus muscles were completely removed, homogenised, and the supernatant was used to the determination of biochemical parameters: N-acetyl-glucosaminidase and mieloperoxidase at different evaluation moments (0, 24 and 48 hours after injection). Cross sections and longitudinal sections of soleus fibers were morphometrically evaluated using a light microscope for an estimation of the percentage of fibers showing any structural alterations (alterations of the striation pattern, sarcoplasmic vacuolisation, segmental necrosis and central nuclei). Ultrathin sections were examined in a Hitachi H9000-NA electron microscope for a qualitative evaluation of the ultrastructure alterations. It was shown that MDMA produces a toxic effect on muscle fibers, observed by the creatine kinase release 90 minutes after the injection, for all o the experimental groups. It was also verified that MDMA produced a significant hyperthermic effect in the animals. The morphological evaluation demonstrated that MDMA induce an extense muscle damage, exposed by the number of damaged fibers. Furthermore, the MDMA administration results in a lymphocyte infiltrate, 24 hours after exercise, observed in the muscle fibers cross sectional areas. These cells were progressively replaced by neutrophils or macrophages, as demonstrated by the activities of myeloperoxidase and N-acetyl-? - glucosaminidase. It can be concluded that the administration of MDMA produced an extreme muscle injury longer in the animals that were submitted to a simultaneous physical exercise, which denotes a more damaging process.
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Hoshi, Rosa. "The neuropharmacological, cognitive and mood effects of ±3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy')." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445586/.
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This thesis investigates the sub-acute and long-term neuropharmacological, cognitive and mood effects of ecstasy use. The first Positron Emission Tomography (PET) study used the 18F-dopa ligand to assess presynaptic dopaminergic function in ex-ecstasy users, poly-drug controls and drug-naive controls. Increased F-dopa uptake was found in the putamen of ex-ecstasy users compared to controls. This could suggest a compensatory upregulation of the dopaminergic system. The second PET study used the 11CDASB ligand to assess 5- HT transporter density in ex-ecstasy users, poly-drug controls and drug-naive controls. No significant group differences indicated recovery of 5-HT transporter density following cessation of ecstasy use, replicating several very recent studies. Studies 3 and 4 assessed cognitive function and aggressive cognitive bias respectively in ex-ecstasy users, current ecstasy users, poly-drug controls and drug- naive controls. A general tendency towards impaired learning and memory in all 3 drug using groups suggested that drug use in general rather than ecstasy use per se could be responsible. In addition, recent drug use was associated with poorer memory performance and impaired response inhibition. No group differences were observed in aggressive cognitive bias. However, Study 5, using the same task with over 100 participants showed increased aggressive interpretative bias (and increased self-rated aggression and depression) 4 days after acute ecstasy use. No evidence of gender differences was found. Study 6 built on findings with serotonergic challenges to explore transient 5-HT depletion. As predicted, on the night of ecstasy use participants showed subtly elevated fear recognition accuracy and the reverse 4 days later. In summary, evidence of recovery of serotonergic function following cessation of ecstasy use should be viewed alongside long-lasting alterations in dopaminergic function. Cognitive 'deficits' are less apparent when ecstasy users are matched with controls for use of all other recreational drugs. 'Mid-week' lowering of mood is now one of the most replicated findings within the ecstasy literature.
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Soar, Kirstie. "Problematic and non-problematic ecstasy (MDMA) usage : cognitive and psychopathological aspects." Thesis, University of East London, 2005. http://roar.uel.ac.uk/3408/.
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This research thesis aimed to explore the apparent dichotomy of ecstasy (MDMA) users who report cognitive and psychopathological problems which they attribute to their use of this drug ("problematic" users), and those who report no adverse ecstasy-related effects ("nonproblematic" users). In the first study, possible psychological sequalae linked to past ecstasy use were assessed in problematic and non-problematic ecstasy users using the modified Brief Symptom Inventory, aspects of the Rivermead Behavioural Memory Test, Tower of London and Auditory Verbal Learning Task. Problematic ecstasy users displayed higher psychopathological symptoms and a small number of selective cognitive deficits compared to non-problematic ecstasy users and polydrug controls. However, problematic ecstasy use did not appear to be related to patterns of ecstasy use or polydrug use. Using the same assessment measures, a case study based on a heavy problematic ecstasy user (RW), who had been abstinent for seven years, was presented. RW displayed cognitive deficits and extensive psychological problems suggesting that heavy ecstasy consumption may be associated with irreversible problems. The persistence of possible psychological and cognitive problems was further investigated in the second group study, using the same battery of tests. However no significant differences in cognitive and psychopathological performances were found between polydrug controls, current and ex-ecstasy users. It is argued that impairments in performance were possibly masked by poor cognitive performance in polydrug controls. The validity of the polydrug control group was addressed (in the third study) by assessing 20 drug-naive participants on the same measures. The introduction of a drug-naive control group only suggested that problematic and non-problematic ecstasy users were exhibiting more errors on the Tower of London task compared to polydrug and drug-naive controls. The final study assessed psychopathological symptoms in problematic and non-problematic ecstasy users relative to drug-naive and polydrug controls, and explored factors which may be integral in the development of problematic ecstasy use, including certain pre-existing factors. Users were assessed on the BSI and Locus of Control scale. Pre-existing psychiatric histories, the intensity of ecstasy dosing and the role of polydrug use in relation to ecstasy use, appeared to contribute in higher psychopathological symptoms in problematic ecstasy users. Together these studies suggest that only self-reported problematic ecstasy users consistently display cognitive and psychopathological problems. For these vulnerable individuals the intensity of ecstasy use, patterns of other drug use and pre-existing psychiatric histories are thought to contribute to the development of these problems.
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Beveridge, Thomas James Ramsey. "An investigation into the neuronal activity induced by direct and indirect 5-HTâ‚‚ agonists as indicated by Arc mRNA." Thesis, De Montfort University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271936.
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O'Mahony, Brian. "Clinical and toxicological significance of the involvement of the cytocrhome p450 system in the metabolism of 3,4-methylenedioxymethamphetamine." Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7209.
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La 3,4-metilenodioximetanfetamina (MDMA, éxtasis) es una anfetamina sustituida de consumo frecuente y abusivo. La enzima principal que participa en el metabolismo de fase I de la MDMA, la isoforma 2D6 (CYP2D6) del citocromo P450, resulta también inhibida por la MDMA. Además, ésta es a la vez metabolizada por otras isoformas de CYP, por ejemplo la CYP1A2. La contribución de esta enzima y los posibles cambios en su actividad tras una administración de MDMA nunca han sido estudiados in-vivo. En consecuencia, se realizó un ensayo clínico donde los marcadores, dextrometorfano y cafeína se administraron tras una dosis oral de MDMA. En base a la farmacocinética de ambos marcadores se evaluaron posibles cambios en la actividad de las enzimas. En base al ratio metabólico urinario de dextrometorfano i dextrorfano (MR) se calculó la vida-media de degradación de CYP2D6. Tras una dosis de MDMA, el Cmax i AUC del dextrometorfano aumentó aproximadamente 10 veces con la correspondiente disminución en los parámetros farmacocineticos de dextrorfano. Se aumentó el MR casi 100 veces después de una dosis de MDMA, con un 67% de los sujetos superando la antimoda de 0.3 para la asignación del fenotipo de metabolizador lento de CYP2D6. La actividad de CYP2D6 se recuperó después de 10 días con una vida media de degradación de CYP2D6 de 46.6 h. La farmacocinética de la cafeína y sus metabolitos no fue afectada por la MDMA. Se debería avisar los consumidores de MDMA de las consecuencias de tal inhibición. A pesar de que hay muchas evidencias en animales sugiriendo que el MDMA es una neurotoxina serotonergica, todavía hay mucho debate sobre cuál es la causa de estos cambios cerebrales a largo plazo. La investigación apunta a la producción excesiva de especies reactivos de oxigeno (ROS) en el cerebro después de la administración de MDMA. La MDMA induce hipertermia, la liberación excesiva de dopamina cerebral y lleva a la desregulación energética del metabolismo. Conjuntamente, el metabolismo de MDMA produce un catecol reactivo, cuyos productos causan neurotoxicidad serotonergica en ratas. Cualquiera de los factores anteriores podrían ser la causa de la excesiva producción de ROS y los consecuentes cambios serotonergicos. A tenor de estas hipótesis, se investigó si diferentes temperaturas corporales afectarían el metabolismo de MDMA. Se administró MDMA a ratas a tres temperaturas ambientales distintas con el fin de prevenir o exacerbar la hipertermia inducida por MDMA. Se determinaron las concentraciones plasmáticas de MDMA y sus metabolitos principales durante las 6 h posteriores a la administración de la droga. Después de siete días, se sacrificaron los animales y se determinaron las cantidades de índoles cerebral. La administración de MDMA a 15ºC bloqueó la respuesta hipertermica y la disminución a largo plazo de 5-HT encontrada en ratas administradas a 21.5 ºC. A 15ºC, las concentraciones plasmáticas de MDMA aumentaron significativamente mientras que las concentraciones de sus metabolitos disminuyeron en comparación con ratas administradas a 21.5ºC. En contraste, la hipertermia y las deficiencias de indoles fueron exacerbadas en ratas tratadas a 30ºC. Se observó que las concentraciones plasmáticas de metabolitos de MDMA aumentaron significativamente en estos animales. La depleción a largo plazo de 5-HT no estuvo potenciada por la perfusión intrastriatal de MDMA después de una dosis sistémica de MDMA. Además, la interferencia del metabolismo de MDMA con la administración del inhibidor de catecol-o-metiltransferasa, entacapona, potenció la neurotoxicidad de MDMA, indicando que los metabolitos que son sustratos para este enzima podrían contribuir a la neurotoxicidad. Estos resultados tienen implicaciones tanto con el papel de la temperatura en el mecanismo del desarrollo de la neurotoxicidad del MDMA como en el abuso en humanos donde la hipertermia esta asociado con casos de toxicidad aguda. Se ha sugerido también que la causa de la depleción de 5-HT por MDMA es debido a un aumento de niveles de tirosina en el cerebro, cuyo hidroxilación no enzimática conduce a la formación de radicales libres derivados de la dopamina. En consecuencia, se propuso que el metabolismo de MDMA en compuestos pro-oxidantes fuera el paso limitante del proceso. En una serie de experimentos se encontraron niveles más altos de hipertermia aguda, concentraciones plasmáticas de tirosina, MDMA y sus metabolitos después de una dosis toxica de MDMA (15 mg/kg i.p.) versus una dosis no-toxica (7.5 mg/kg i.p.). La administración de una dosis no-toxica de MDMA (7.5 mg/kg i.p.) en conjunto con L-tirosina (0.2 mmol/kg i.p.) produció un aumento similar de niveles de tirosina en el suero con los niveles encontrados tras una dosis toxica de MDMA, sin embargo, los niveles de 5-HT cerebral permanecieron en niveles normales. Una dosis no-toxica de MDMA en combinación con una dosis alta de tirosina (0.5 mmol/kg i.p.) causó depleciones a largo plazo en ratas administradas a 21.5ºC pero no a 15ºC, condiciones conocidas por disminuir el metabolismo de MDMA. Al mismo tiempo, la perfusión estriatal de MDMA en combinación con tirosina (0.5 mmol/kg i.p.) en ratas hipertermicas no causaron depleciones de 5-HT. En contraste, se observaron reducciones significativas en 5-HT cerebral tras la administración de una dosis no-toxica de MDMA en ratas en condiciones de hipertermia en combinación con entacapona o acivisina, compuestos capaces de interferir con el metabolismo de MDMA o aumentar la disponibilidad de sus metabolitos en el cerebro, respectivamente. En conjunto estos datos indican que a pesar de que la tirosina y la hipertermia pueden contribuir a la neurotoxicidad inducida por la MDMA, el metabolismo de la droga parece ser el paso limitante.
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Montgomery, Catharine Anne. "The differential effects of MDMA (ecstasy) use on executive and memory processes." Thesis, Liverpool John Moores University, 2006. http://researchonline.ljmu.ac.uk/5775/.
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The purpose of this thesis was to examine the nature of executive function deficits in ecstasy users, and the contribution of these executive functions to performance on other cognitive tasks. Using recent theoretical models of executive functioning recreational ecstasy-polydrug users were tested in laboratory settings on measures of mental set switching, response inhibition, memory updating and access to semantic memory. It was found that ecstasy users performed significantly worse than nonusers on measures of updating and access, although cocaine also emerged as an important factor in deficits in access. The contribution of access and updating to performance on more complex executive function tasks was then assessedI.t was found that while associative learning is relatively independent of access and updating, the same was not true for everyday memory and syllogistic reasoning. Ecstasy group related deficits in syllogistic reasoning were slightly attenuated following control for access and substantially following control for updating. It emerged that everyday memory deficits were more related to the use of cannabis than the use of ecstasy. The results of this thesis have serious implications for those who use ecstasy and should be used in educating such individuals. Outside the area of Psychopharmacology this thesis provides further support for the nature of executive functions and their relationship with syllogistic reasoning and everyday memory. Future research should assess executive functions along the same paradigm and seek to recruit polydrug control groups.
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Nair, Sunila. "Effects of 3,4-methylenedioxymethamphetamine (MDMA) on Cholinergic neurons in the rat brain." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123857787.
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Battisti, Murilo Campos [UNIFESP]. "Seguimento por cinco anos de uma amostra de usuários de ecstasy (MDMA)." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/10070.
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Made available in DSpace on 2015-07-22T20:50:47Z (GMT). No. of bitstreams: 0
Previous issue date: 2009-06-24Ecstasy (MDMA) é uma droga que possui importante ação neurotóxica. O seu uso é descrito como um fenômeno jovem. A pesquisa teve por objetivo estudar longitudinalmente uma amostra de usuários de ecstasy entrevistada em 2001 em São Paulo e re-entrevistada entre 2005 e 2006 a fim de observar mudanças no padrão de consumo da droga. A coleta de dados ocorreu por meio de entrevistas semi-estruturadas e casos de dependência foram avaliados por meio do DSM-IV. Utilizou-se a metodologia qualitativa com duas fases de entrevista: entrevista inicial (32 entrevistados) e follow-up (21 re-entrevistados). As entrevistas foram gravadas, transcritas literalmente e submetidas à análise de conteúdo. A média de idade da amostra foi de 24,8 anos na fase inicial e 28,7 anos na fase follow-up. Três cenários foram observados: a) uso transicional (n=14) – marcado por acentuada redução ou abandono do consumo de ecstasy ao longo do período investigado; b) uso habitual de longo prazo (n=06) - manutenção no padrão de consumo de ecstasy ou discreta moderação; uso compulsivo de longo prazo (n=01) – aumento em mais de 50% no consumo de ecstasy ao longo dos anos. O uso de álcool e maconha manteve-se inalterado ao longo do período investigado. Quatro sujeitos relataram aumento no consumo de cocaína e seis fizeram menção à iniciação no uso de metanfemina. Observou-se que para uma parte dos entrevistados o ecstasy se caracterizou como uma droga transicional. Para outro grupo o uso de ecstasy se caracterizou por ser uma experiência duradoura.
Ecstasy (MDMA) is an important neurotoxic agent. Its use is described as a youth-limited phenomenon. The aims were to determine the natural course of ecstasy use within a five year timeframe in a sample of Brazilian young adults and to assess changes in ecstasy use patterns. Interviews took place in two waves: 2001 in São Paulo and in 2005/06. Data collection occurred through semi-structured interviews. The DSM-IV was used to assess ecstasy dependence. Qualitative method was utilized during the baseline sample (n=32) and the follow-up sample (n=21). All interviews were fully recorded, transcribed and interpreted though content analysis. Subjects’ average age was 24.8 years in the baseline group and 28.7 years in the follow-up. Three scenarios emerged: (A) the transient use group (n=14) either quit using ecstasy or cut down use significantly; (B) the long term habitual use (n=06) group maintained or cut down slightly on MDMA use; (C) the compulsive use group (n=01) increased ecstasy use by more than 50% over the course of the study. As ecstasy use shifts occurred, alcohol and marijuana consumption remained unaltered. Four respondents reported increases in cocaine use, and six subjects mentioned initiation in crystal methamphetamine use. For a group of respondents ecstasy use was a transient phenomenon. For another group of subjects MDMA use manifested as a lasting experience.
TEDE
BV UNIFESP: Teses e dissertações
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Kohutek, Jodi Lynn. "Long-term effects of 3,4- Methylenedioxymethamphetamine (MDMA) on serotonergic and dopaminergic functioning." CSUSB ScholarWorks, 2003. https://scholarworks.lib.csusb.edu/etd-project/2305.
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Methylenedioxymethamphetamine (MDMA) popularly known as "Ecstasy" continues to gain popularity as a recreational drug that has been shown to increase serotonin and dopamine levels. The present study has demonstrated that repeated exposure to MDMA produces long-term damage to serotonergic and dopaminergic neurons in various regions of the rat brain.
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Brown, John Anthony, and John Brown@anu edu au. "The pattern of memory and perceptual dysfunctions in recreational ecstasy users." The Australian National University. Faculty of Science, 2006. http://thesis.anu.edu.au./public/adt-ANU20060407.155643.
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There is a growing body of evidence that the main psychoactive ingredient of the recreational drug ecstasy (methylendioxymethamphetamine; MDMA) causes lasting changes to the serotonin system in both animals and humans, including the hippocampus (involved in memory) and the occipital lobe (involved in visual perception). Previous studies have often found memory deficits in ecstasy users. However, the results have been far from consistent across studies. None of the methods used to date have adequately isolated the hippocampal component of memory from the contribution of other brain regions. Three memory studies were conducted in this thesis to clarify which components and processes of memory are in deficit in ecstasy users.¶
In the first memory study, ecstasy users (n=32) did not differ from non-drug using controls (n=29) on implicit memory (automatic non-conscious retrieval, as revealed by a stem-completion task), or explicit memory (conscious recollection, as revealed by stem-cued recall). In the second memory study, no significant differences were found between ecstasy users (n=30) and non-drug using controls (n=34) on tests designed to clarify the findings on explicit memory, or on two standard neuropsychological tests of long-term memory (prose recall and Auditory Verbal Learning Test) that allowed greater use of elaborative processing at study. In the third memory study, a number of tests were applied that differed in their elaborative processing demands, including the California Verbal Learning Test, Visual Paired Associates, and Verbal Paired Associates. Ecstasy users (n=32) had poorer recall, and made less strategic use of elaborative processing compared to both cannabis-using controls (n=33) and non-drug using controls (n=33). Also, on a novel test of elaborative processing (Verbal Triplet Associates), both cannabis users and ecstasy users had memory deficits on the first trial, but only ecstasy users had a significant learning deficit over successive trials. On the basis of the localisation of the components and processes of memory in literature, it was concluded that long-term memory deficits in ecstasy users may reflect changes in elaborative processes localised in the frontal lobes, or global deficits, rather than just changes to the memory functions of the hippocampus.¶
With regard to visual perception, no studies have been published to date that have examined MDMA-related changes to the behavioural functioning of the occipital lobe in humans. In the current thesis, this was investigated using the tilt aftereffect illusion. In accordance with expectations, ecstasy users had a larger tilt aftereffect compared to non-drug using controls (n=34). Unexpectedly, this result was only obtained for a subset of 12 ecstasy users (out of n=30) who had not used amphetamines in the recent past. It was concluded that the results for ecstasy users who had not recently used amphetamines were consistent with the proposal that ecstasy-related serotonergic changes in the occipital lobe broaden the tuning bandwidth of orientation sensitive neurons, and that the recent use of amphetamines appears to counteract that effect.
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Davis, Alan Kooi. "Development and Initial Evaluation of an Ecstasy Craving Questionnaire." Bowling Green State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1335999475.
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Tomillero, Alemany Àngels. "Farmacología clínica de la Metilenodioximetanfetamina (MDMA, éxtasis) tras su administración a dosis repetidas." Doctoral thesis, Universitat Autònoma de Barcelona, 2001. http://hdl.handle.net/10803/5368.
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El consumo de 3,4-metilendioximetanfetamina (MDMA o éxtasis) se realiza habitualmente en ambientes festivos y es frecuente el uso de varias dosis a lo largo de una noche de fiesta. En la literatura científica no se han descrito hasta la fecha estudios controlados a dosis repetidas de MDMA que permitan vislumbrar sí con el consumo repetido de esta sustancia aparecen fenómenos de tolerancia o sensibilidad que puedan favorecer la presentación de toxicidad. El objetivo de esta Tesis fue conocer la farmacología de la MDMA tras la administración de dos dosis consecutivas de MDMA separadas por un intervalo de cuatro horas, profundizando especialmente en su farmacocinética y en la posible aparición de fenómenos de tolerancia aguda. Se diseñó un ensayo clínico a doble ciego, cruzado, controlado con placebo, con asignación aleatoria de las condiciones de tratamiento según un cuadrado latino de 4x4 balanceado. Participaron un total de ocho voluntarios sanos consumidores habituales de MDMA. Cada sujeto participo en cuatro sesiones, una para cada condición de tratamiento, separadas por al menos una semana de periodo de blanqueo. Las cuatro condiciones de tratamiento fueron: MDMA 100 mg + placebo (MDMA primera administración); placebo + MDMA 100 mg (MDMA segunda administración), MDMA 100 mg + MDMA 100 mg (MDMA dosis múltiple) y placebo + placebo (Placebo).
Tras la administración repetida se observaron aumentos significativos de la presión arterial sistólica, la frecuencia cardiaca y la temperatura respecto a la dosis única. Estos aumentos no alcanzaron los esperables por el principio de superposición o suma simple de los efectos de las dos dosis. En el caso de la presión arterial diastólica la segunda administración de la dosis múltiple registró aumentos similares a los esperados por superposición. Ello sugiere que podría existir tolerancia aguda en algunas de estas variables. El rendimiento psicomotor y la tensión muscular medida por la esoforia en el ala de Maddox mostraron cambios significativos respecto a la dosis única. Los incrementos fueron incluso mayores de los esperables por el principio de superposición tras la dosis repetida. No parece existir tolerancia, y en el caso de la tensión muscular podría incluso existir una posible sensibilización. En el caso de los efectos subjetivos, la dosis repetida produjo globalmente incrementos mayores que la dosis única en las escalas de euforia, estimulación, efectos desagradables y cambios en las percepciones. En el caso de los efectos de euforia y estimulación fueron parecidos a los previstos según el principio de superposición. En ningún caso se presentaron alucinaciones ni síntomas sugestivos de alteraciones psicóticas. Las concentraciones plasmáticas de cortisol y prolactina tras la dosis repetida fueron similares a las obtenidas tras una dosis única, sugiriendo tolerancia.
La concentración plasmática máxima de la MDMA tras la segunda administración de la dosis repetida superó en un 20% la que hubiera sido esperable por la suma de las dos dosis administradas. En cuanto a la concentración de HMMA, prácticamente no aumentó tras la segunda dosis, observándose niveles similares a los obtenidos tras una dosis única y por ello un 45 % menores de los esperados. La formación de la HMMA parece inhibirse por la presencia previa de MDMA y/o sus metabolitos. Integrando los efectos farmacológicos y las concentraciones plasmáticas de MDMA, se observa una clara tolerancia aguda en todas las variables estudiadas excepto para la tensión muscular y el rendimiento psicomotor.
La administración de dos dosis consecutivas de MDMA produce una cierta acumulación en las concentraciones plasmáticas de MDMA pero globalmente los efectos farmacológicos son menores de los esperables para esas elevadas concentraciones. Todo ello sugiere la aparición de un fenómeno de tolerancia aguda, que posiblemente es de origen farmacodinámico.
3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is usually consumed in multiple doses along a party session. Till now there aren´t published controlled clinical trial after repetated administration looking for the presentation of acute tolerance or up-regulation that implies toxicity. The goal of this thesis was know the pharmacology of MDMA after repeated administration with an interval of four hours between doses considering pharmacokinetic and the possibility of acute tolerance.
The study design was double-blind, randomized, crossover, and controlled. Treatment conditions were randomly using a balanced 4x4 Latin -square design. Eight healthy male recreational MDMA users participated in four sessions with a 1-week washout period. They were administered twice with a 4 hours interval on each of four experimental sessions. Drug conditions were: MDMA 100mg+ placebo(MDMA first dose), placebo+ MDMA 100mg (MDMA second dose), MDMA 100mg+MDMA 100mg (MDMA repeated administration) and placebo+ placebo (placebo).
Repeated administration significantly increased sistolic blood presure, heart rate and temperature as compared with the first administration. These increases didn´t reach the expected by the superposition criteria. The diastolic blood presure after the second administration increased like the expected by superposition criteria. There were acute tolerance in some of these physiological variables. Psychomotor performance and muscular tension measured by the esoforia in the Maddox -wing increased more than expected considering the pharmacokinetic superposition criteria. Maddox-wing and psychomotor tasks seemed not to be affected by acute tolerance and in the Maddox -wing probably there were a up-regulation phenomenon.
Subjective effects after the repeated administration were increased more as compared with the first administration in scales related to euphoria, stimulated, bad effects and changes in perceptions. The effects related to euphoria and stimulated were similar with the expected by the superposition criteria. No hallucinations or psychotic episodes were observed among subjects during the study.
Plasma concentrations of cortisol and prolactina after the repeated administration were similar as compared with the concentrations after the first administration, this suggested the development of tolerance.
Peak concentration of MDMA after the second administration of the repeated administration was 20% higher than the expected by the superposition criteria. Peak concentration of HMMA after the repeated administration was 45% lower than the expected, this metabolite maybe inhibited by his precursor MDMA or their metabolites.
In summary, the pharmacologic effects observed in relation with the plasma concentrations of MDMA, suggested the development of almost complete tolerance for all the variables essayed except Maddox-wing and psicomotor performance.
Repeated administration of MDMA made plasma accumulation of MDMA but the pharmacologic effects were fewer than expected by these higher concentrations. All of this suggested the development of acute tolerance maybe pharmacodynamic.
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Segura, Agulló Mireia. "Interacció farmacològica entre la 3.4-Metilendioximetamfetamina (MDMA, Èxtasi) i la paroxetina en humans." Doctoral thesis, Universitat Pompeu Fabra, 2004. http://hdl.handle.net/10803/7077.
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La 3,4-metilendioximetamfetamina (MDMA, èxtasi) és una droga de síntesi que es consumeix entre els joves de forma recreativa. S'ha postulat que la 3,4-dihidroximetamfetamina (HHMA), metabòlit que es forma a partir de l'O-demetilenació de la MDMA a través majoritàriament de l'isoenzim CYP2D6, podria tenir un paper important en el desenvolupament de la neurotoxicitat atribuïda a la MDMA. Així, un dels objectius de la tesi ha estat establir quin paper juga i quina importància té, des d'un punt de vista quantitatiu, aquest metabòlit HHMA en el metabolisme global de la MDMA in vivo. Per altra banda, el CYP2D6 és un enzim polimòrfic, i potencialment els subjectes metabolitzadors lents per aquesta acitivitat enzimàtica podrien tenir un risc més alt de patir toxicitat aguda. La MDMA es consumeix sovint concomitantment amb inhibidors selectius de la recaptació de serotonina (SSRI). Alguns SSRI, com la paroxetina i la fluoxetina, són inhibidors del CYP2D6 i es pot preveure una interacció metabòlica entre aquests tipus de substàncies. Mitjançant un assaig clínic (aleatori, doble cec, creuat i controlat amb placebo) en humans, s'ha estudiat la rellevància de la inhibició de l'activitat del CYP2D6, la seva contribució en el metabolisme de la MDMA i els efectes farmacològics que resulten de la co-administració de la MDMA i la paroxetina.Han estat determinades les concentracions plasmàtiques i urinàries de la MDMA i dels metabòlits més importants de la MDMA, així com les concentracions plasmàtiques de paroxetina juntament amb el seu metabòlit principal.
Dels resultats obtinguts, la tesi conclou que l'HHMA és un metabòlit rellevant en la disposició metabòlica de la MDMA. L'estudi d'interacció mostra que la MDMA veu reduït el seu metabolisme oxidatiu al voltant d'un 30% i que ambdós compostos mostren una interacció metabòlica. El CYP2D6 podria contribuir in vivo en l'O-demetilenació de la MDMA en un 30%.
3,4-methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative misused among youths for recreational purposes. It has been postulated that 3,4-dihydroxymethamphetamine (HHMA), a metabolite resulting from the O-demethylenation of MDMA through CYP2D6 may play a role in the development of the neurotoxicity. Thus, one of the major aims of the thesis was to establish HHMA relevance, from a quantitative point of view, in MDMA metabolism. Moreover, CYP2D6 is a polymorphic enzyme and the participation of CYP2D6 in the oxidative metabolism of MDMA may suggest an increased risk for acute toxicity in poor metabolizers for this enzymatic activity. MDMA is sometimes consumed concomitantly with selective serotonin reuptake inhibitors (SSRI). Some SSRI are potent CYP2D6 inhibitors such as paroxetine or fluoxetine and a metabolic interaction between these drugs and MDMA could be expected. Thus, interaction studies of MDMA with SSRI may be an in vivo approach to evaluate the contribution of CYP2D6 on MDMA disposition and the effects of the co-administration of both compounds. The major objective was to assess the contribution of CYP2D6 to MDMA disposition using paroxetine as a metabolic probe inhibitor. It was carried out a clinical trial in humans. The study was randomized, double blind, crossover, and controlled with placebo.
Plasma concentration-time profiles and urinary recoveries of MDMA and main metabolites including HHMA were obtained. Paroxetine and its main metabolite (hydroxy-methoxy-paroxetine) plasma concentrations were also determined.
From the results obtained, it is conclude that HHMA is a relevant metabolite on MDMA disposition in humans. The interaction study shows a 30% reduction of MDMA metabolic disposition and both MDMA and paroxetine show a pharmacodynamic interaction. It is estimated that CYP2D6 may accounts for a 30% of MDMA O-demethylenation in humans.
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Pizarro, Lozano Mª Nieves. "La Influència de l'estereroquímica en el metabolisme de la 3,4-metilendioximetamfetamina (MDMA, èxtasi)." Doctoral thesis, Universitat Pompeu Fabra, 2004. http://hdl.handle.net/10803/7079.
Full textAbstract:
La MDMA és cap de sèrie dels entactògens. El seu consum provoca toxicitat aguda i neurodegeneració a mig/llarg termini del sistema serotoninèrgic. Es postula que la bioactivació metabòlica podria ser responsable del desenvolupament de neurotoxicitat.La MDMA té un centre estereogènic. Es consumeix com a racemat, però els enantiòmers tenen perfils farmacològics diferenciats. A més, la MDMA té una depuració metabòlica enantioselectiva i autoinhibible (CYP2D6).
Aquesta tesi presenta l'enantioselectivitat de la depuració metabòlica de la MDMA en consumidors recreatius participants d'un assaig clínic (dosi: 100 mg).
Es sintetitzà material de referència i es desenvolupà metodologia per a l'anàlisi enantioselectiu i diastereoselectiu dels compostos.
S'estudià l'enantioselectivitat en el metabolisme fins a 48h post-administració, obtenint-se raons (R)-MDMA/(S)-MDMA>1 i en augment amb el temps. Les raons del metabòlits majoritaris foren pràcticament constants i properes a 1, possiblement degut a la inhibició metabòlica del CYP2D6 i a la participació d'altres enzims no enantioselectius.
La MDMA es la cabeza de serie de los entactógenos. Su consumo provoca toxicidad aguda y neurodegeneración serotonérgica a medio/corto plazo. Se postula que una bioactivación metabólica podría ser responsable del desarrollo de neurotoxicidad.
La MDMA tiene un centro estereogénico. Se consume como racemato, pero los enantiómeros tienen perfiles farmacológicos diferenciados. Además, presenta depuración metabólica enantioselectiva y autoinhibible (CYP2D6).
Esta tesis presenta la enantioselectividad de la depuración metabólica de la MDMA en consumidores recreativos participantes de un ensayo clínico (dosis: 100 mg).
Se sintetizó material de referencia y se desarrolló metodología para el análisis enantioselectivo y diastereoselectivo de los compuestos.
Se estudió la enantioselectividad en el metabolismo hasta 48h post-administración, obteniéndose relaciones (R)-MDMA/(S)-MDMA>1 y en aumento con el tiempo. Las relaciones de los metabolitos mayoritarios fueron prácticamente constantes y cercanas a 1, posiblemente debido a la inhibición metabólica del CYP2D6 y a la participación de otros enzimas no enantioselectivos.
MDMA is the head of entactogenic compounds. Its consumption causes acute toxicity and mid/long term serotonergic neurodegeneration. It is postulated that a metabolic bioactivation may be responsible for development of neurotoxicity.
MDMA has a stereogenic center. It is consumed as a racemate, but its enantiomers have different pharmacological profiles. Also, MDMA presents an enantioselective and self-inhibited metabolic disposition (CYP2D6).
The present thesis shows data about enantioselective metabolic disposition of MDMA in recreative consumers that participated in a clinical trial (dose: 100 mg).
It was synthesised reference material and it was developed methodology for both enantioselective and diastereoselective analysis MDMA and its main metabolites.
It was studied the enantioselectivity in the metabolism after 48h post-administration. (R)-MDMA/(S)-MDMA ratios were >1 and increasing over time. Major metabolites ratios were practically constant and close to 1, possibly because of the metabolic inhibition of CYP2D6 and the role of other non-enantioselective enzymes.
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Pachmerhiwala, Rashida. "Relationships between MDMA induced increases in extracellular glucose, glycogenolysis in brain and hyperthermia." Cincinnati, Ohio : University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204751566.
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Thesis (M.S. of Pharmaceutical Sciences)--University of Cincinnati, 2008.Advisor: Gary Gudelsky PhD. Title from electronic thesis title page (viewed May 7, 2008). Includes abstract. Keywords: MDMA, glucose, serotonin, norepinephrine,glycogenolysis,hyperthermia. Includes bibliographical references.
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Kolyaduke, Olga. "Long term effects of MDMA administration in rats during early and late adolescence." Thesis, University of Canterbury. Psychology, 2011. http://hdl.handle.net/10092/5571.
Full textAbstract:
Drug use and abuse for recreational purposes is a common phenomenon, with club drugs such as MDMA (3,4-methylendioxymethamphetamine) being popular for its energetic and euphoric effects – recreating an artificial feeling of “Ecstasy”. Although use of the drug itself has remained relatively constant over the years, the population among which it is popular has been shifting toward younger users, with MDMA use among adolescents becoming more prominent. However research on the effects that MDMA has on the developing adolescent brain has been limited. The current study focuses on the long term effects in rats following chronic MDMA exposure during either early or late adolescence. In adulthood, the rats’ memory, activity and emotional reactivity were assessed through frequency of ambulation, grooming, rearing, defecation, and corner or center occupancy of an open-field, novel object-recognition in the open-field, emergence from a dark chamber into a bright area, and recognition of the changed arm of the Y-maze. The results showed that there were significant long-term effects resulting in increased anxiety for rats treated with MDMA during late adolescence only. This increase of emotional reactivity was indicated through decreased ambulation on the open-field measures, decreased movement between the dark and light chambers, and decreased entries of both arms of the Y-maze. Sex of the animal was also found to differentiate MDMA effects, with females showing a greater increase in anxiety. Measures regarding spatial and working memory were not significant. Overall, the results suggest that animals are more susceptible to long-term effects following MDMA administration in late, but not early adolescence. Furthermore, memory appears to remain unaffected regardless of the age of administration, and only anxiety levels were affected by the drug.
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Saadat, Kathryn S. "Studies on the acute and long-term effects of MDMA (3, 4- methylenedioxymethamphetamine)." Thesis, De Montfort University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438901.
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Sola, Evan M. "MDMA-Assisted Psychotherapy for PTSD| A Thematic Analysis of Transformation in Combat Veterans." Thesis, California Institute of Integral Studies, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10813306.
Full textAbstract:
Post-traumatic stress disorder (PTSD) is a common psychological effect of military combat. However, little empirical research has been done to highlight specific complications and needs in treating this population, and even less has been done using the psychedelic drug MDMA. This study used the qualitative research method of thematic analysis to explore the lived experiences of combat veterans engaged in MDMA-assisted psychotherapy for PTSD. This study reviewed video, as well as narrative data from MDMA psychotherapy sessions. Thematic analysis was used to analyze the transcribed audio data. The specific primary aim of the present study was to investigate the following research question: What is the lived experience of combat veterans in MDMA-assisted psychotherapy sessions, and how can this experience be understood through a psychotherapeutic perspective on well-being? Exploration of psychoanalytic and transpersonal aspects of the psychotherapy process are highlighted in their facilitation of healing in combat veterans.
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Renoir, Thibault. "Mécanismes sérotoninergiques sous-tendant les effets de la MDMA ("ecstasy") chez la souris." Paris 5, 2008. http://www.theses.fr/2008PA05P608.
Full textAbstract:
Nous avons évalué les effets renforçants de la MDMA via une procédure d’auto-administration couplée à la technique de microdialyse. Les modifications qui suivent un traitement avec la MDMA ont également été étudiées. Nous montrons que les souris 5-HTT-/- ne s’auto-administrent pas la MDMA contrairement à leurs congénères sauvages. Les données obtenues par microdialyse montrent que les effets renforçants de la MDMA sont liés à l’induction de la libération de sérotonine par cette drogue. Nous démontrons l’existence d’une hypersensibilité de l’autorécepteur 5-HT1A chez des souris sauvages 28 jours après MDMA, ainsi qu’une baisse des taux tissulaires de sérotonine. Ce traitement à la MDMA provoque une baisse de la prolifération cellulaire. Utilisant le test de la nage forcée, nous mettons en évidence un allongement du temps d’immobilité chez les souris traitées par la MDMA. Ces modifications qui révèlent une action dépressiogène de la MDMA, ne sont pas observées chez les souris 5-HTT-/-The appetitive effects of MDMA have been evaluated using self-administration and microdialysis procedure. We’ve also studied putative long term adaptative changes following MDMA teatment. Our data show that 5-HTT-/- mice did not self-administrate MDMA when wild-type mice did. The absence of self-administration exhibited by 5-HTT-/- mice could be related to the blunted MDMA-induced 5-HT release observed in these same KO mice. About the long term effects of MDMA, we’ve found an increase of 5-HT1A autoreceptor sensitivity associated with a decrease of 5-HT tissue levels. Our data suggest also a decrease of cell proliferation 28 days after the MDMA treatment in WT mice. Finally MDMA-treated mice displayed a depressive-like behavior compared to saline-teated mice using the forced swim test. Interestingly all the adaptative changes following MDMA treatment were observed in WT mice but not in 5-HTT-/- mice
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PACHMERHIWALA, RASHIDA. "Relationships between MDMA induced increases in extracellular glucose, glycogenolysis in brain and hyperthermia." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204751566.
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