Sample records for regular ecstasy mdma

  1. MDMA (Ecstasy/Molly)

    ... MDMA as an illegal drug with no recognized medicinal use. Some researchers remain interested in its value ... Electronic Cigarettes (E-cigarettes) Fentanyl Hallucinogens Heroin Inhalants Marijuana Marijuana as Medicine MDMA (Ecstasy/Molly) Methamphetamine Prescription ...

  2. Ecstasy (MDMA) and oral health

    H.S. Brand; S.N. Dun; A.V. Nieuw Amerongen


    3,4-methylenedioxymethamphetamine (MDMA), more commonly known as 'ecstasy' or XTC, is frequently used by young adults in the major cities. Therefore, it is likely that dentists might be confronted with individuals who use ecstasy. This review describes systemic and oral effects of ecstasy. Life-thre

  3. MDMA and the "ecstasy paradigm".

    Cole, Jon C


    For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

  4. MDMA, cortisol, and heightened stress in recreational ecstasy users.

    Parrott, Andrew C; Montgomery, Cathy; Wetherell, Mark A; Downey, Luke A; Stough, Con; Scholey, Andrew B


    Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress.

  5. MDMA (Ecstasy or Molly)

    ... scene, at “raves” (all-night dance parties), and music festivals or concerts. MDMA’s effects generally last from 3 to 6 hours. MDMA ... causes long-term brain changes or if such effects are reversible when someone ... problems with memory and attention. Learn more about how the brain ...

  6. The case for MDMA (ecstasy) regulation.

    Donelly, Joshua


    Drug-related harm is the most rational means of determining a substance's legal status. The available evidence suggests that compared to other drugs, 3,4-methylenedioxy-N-methamphetamine (MDMA or "ecstasy") poses a low level of harm to most individual users and causes negligible harm to society. There is no sound justification for criminalising the use of MDMA. .The depenalisation model adopted in Australia does not have any benefits that cannot be achieved by removing minor MDMA offences from criminal law entirely. The current model also operates within a prohibition framework that is costly to society and increases harm to ecstasy users. These arguments support the proposal by David Penington in 2012 that MDMA should be regulated on a legal market. The supply of MDMA from pharmacies appears to be a practicable law reform option with the potential to reduce harm associated with ecstasy use and the costs of prohibition.

  7. Neurotoxicity of ecstasy (MDMA): an overview.

    Sarkar, Sumit; Schmued, Larry


    "Ecstasy" (MDMA) is a powerful hallucinogenic drug which has raised concern worldwide because of its high abuse liability. A plethora of studies have demonstrated that MDMA has the potential to induce neurotoxicity both in human and laboratory animals. Although research on MDMA has been carried out by many different laboratories, the mechanism underlying MDMA induced toxicity has not been fully elucidated. MDMA has the ability to reduce serotonin levels in terminals of axons in the cortex of rats and mice. Recently we have shown that it also has the potential to produce degenerate neurons in discrete areas of the brain such as insular and parietal cortex, thalamus, tenia tecta and bed nucleus of stria terminalis (BST). Acute effects of MDMA can result in a constellation of changes including arrthymias, hypertension, hyperthermia, serotonin (5-HT) syndrome, liver problems, seizures and also long lasting neurocognitive impairments including mood disturbances. In human MDMA abusers, there is evidence for reduction of serotonergic biochemical markers. Several factors may contribute to the MDMA-induced neurotoxicity, especially hyperthermia. Other factors potentially influencing MDMA toxicity include monoamine oxidase metabolism of dopamine and serotonin, nitric oxide generation, glutamate excitotoxicity, serotonin 2A receptor agonism and the formation of MDMA neurotoxic metabolites. In this review we will cover the following topics: pharmacological mechanisms, metabolic pathways and acute effects in laboratory animals, as well as in humans, with special attention on the mechanism and pathology of MDMA induced neurotoxicity.

  8. Increased intensity of Ecstasy and polydrug usage in the more experienced recreational Ecstasy/MDMA users: a WWW study.

    Scholey, Andrew B; Parrott, Andrew C; Buchanan, Tom; Heffernan, Thomas M; Ling, Jonathan; Rodgers, Jacqui


    Recreational Ecstasy/MDMA (3,4-methylenedioxymethamphetamine) users often take a variety of psychoactive drugs, but there is little empirical data on how these drug consumption patterns change with greater experience of Ecstasy. The aim of this study was to compare the polydrug usage patterns reported by non-Ecstasy users, novice Ecstasy users, moderate Ecstasy users, and heavy Ecstasy users. In a WWW study of 763 unpaid volunteers, 481 had never taken Ecstasy, whereas 282 reported they had taken it. The Ecstasy users comprised 109 novice users (1-9 occasions), 136 moderate Ecstasy users (10-99 occasions), and 36 heavy Ecstasy users (+100 occasions). Each participant also reported their experience with a range of other psychoactive drugs. The Ecstasy users reported significantly greater psychoactive drug usage than the non-Ecstasy users. The novice, moderate, and heavy Ecstasy users also differed significantly from each other in the use of cocaine, amphetamine, LSD, and psilocybin mushrooms, but not of alcohol, cannabis, or cigarettes/nicotine. Experienced Ecstasy users also took significantly more MDMA tablets on each occasion, and reported a higher maximum weekly intake. The increased use of Ecstasy is associated with more intensive patterns of Ecstasy/MDMA intake, and the greater use of illicit CNS stimulants and hallucinogens, but not of alcohol, nicotine, or cannabis. These results are discussed in the context of cross-tolerance and drug predisposition/preference.

  9. Information processing speed in ecstasy (MDMA) users.

    Wareing, Michelle; Fisk, John E; Montgomery, Catharine; Murphy, Philip N; Chandler, Martin D


    Previous research draws parallels between ecstasy-related and age-related deficits in cognitive functioning. Age-related impairments in working memory have been attributed to a slow down in information processing speed. The present study compared 29 current ecstasy users, 10 previous users and 46 non-users on two tests measuring information processing speed and a computation span task measuring working memory. Results showed that ecstasy users performed worse than non-ecstasy users in the letter comparison task although the overall difference was not significant (p=0.089). Results from the pattern recognition task showed that current ecstasy users produced significantly more errors than the other two groups (pecstasy users produced significantly more errors than non-ecstasy users (pecstasy using groups performing significantly worse than non-users on the computation span measure (pmechanism responsible for impairments in the computation span measure is not the same as that in elderly adults where processing speed generally removes most of the age-related variance. Also of relevance is the fact that the ecstasy users reported here had used a range of other drugs making it difficult to unambiguously attribute the results obtained to ecstasy use.

  10. Multiple molecular and neuropharmacological effects of MDMA (Ecstasy).

    Simantov, Rabi


    3,4-Methylenedioxymethamphetamine (MDMA), commonly referred to as Ecstasy, is a widely abused, psychoactive recreational drug, which induces short- and long-term neuropsychiatric behaviors. This drug is neurotoxic to serotonergic neurons in vivo, and induces programmed cell death in cultured human serotonergic cells and rat neocortical neurons. Over the years it has been shown that MDMA alters the release of several neurotransmitters in the brain, it induces recompartmentation of intracellular serotonin and c-fos, and modifies the expression of a few genes. Recently, we observed changes in gene expression in mice treated with MDMA, and cloned and sequenced 11 cDNAs thus affected (4 correspond to known and 7 to unknown genes). The effect of MDMA on two of these genes, GABA transporter 1 and synaptotagmin IV was studied in detail. Characterization of the relationship between a given gene and certain physiological or behavioral effects of MDMA could shed light on the mechanism of the drug's action. However, establishing such a connection is difficult for several reasons, including that serotonergic neurons are not the only cells affected by MDMA. In this review, molecular and neurochemical events that occur in the brain following exposure to MDMA, and link between the observed molecular changes with known physiological effects of the drug are discussed. It is indicated that MDMA alters the expression of several proteins involved in GABA neurotransmission, thus having critical effect on thermoregulation and MDMA acute toxicity. This analysis should facilitate development of novel approaches to prevent deleterious effects, especially mortality induced by MDMA and other abused psychostimulants.

  11. Neurotoxic effects of MDMA (ecstasy) on the developing rodent brain.

    Dzietko, M; Sifringer, M; Klaus, J; Endesfelder, S; Brait, D; Hansen, H H; Bendix, I; Felderhoff-Mueser, U


    The incidence of methamphetamine abuse is particularly high in adolescents and is a common problem among women of childbearing age, leading to an increasing number of children with prenatal exposure. MDMA (3,4-methylenedioxymethamphetamine, ecstasy) is an amphetamine-like stimulant and is known to induce apoptotic damage to fine serotonergic fibers in the adult rat brain. Little is known about toxic effects of MDMA and potential underlying molecular mechanisms in the developing brain. Here, we investigated whether MDMA exposure during the period of rapid brain growth causes neurodegeneration in the developing rat brain. MDMA significantly enhanced neuronal death in the brains of 6-day-old rat pups at a dose of 60 mg/kg, but no significant toxicity was detected at the ages of 14 and 21 days. Brain regions mainly affected were the cortex, septum, thalamus, hypothalamus and the cornu ammonis 1 region. To explore possible molecular mechanisms involved in this neurodegenerative process, we investigated the impact of MDMA on the expression of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor. Neonatal exposure of 6-day-old rats to MDMA triggered a considerable increase in cortical BDNF and NT-3 levels. Moreover, P7 CD1/BDNF knockout mice were noticeably more sensitive to MDMA exposure as compared to their wild-type age-matched littermates. These data suggest that a single injection of MDMA causes neurodegeneration in the neonatal rat brain. The upregulation of BDNF and NT-3 expression may indicate an important compensatory mechanism leading to the survival of neuronal cells in the developing brain.

  12. Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy.

    Parrott, A C


    This review of chronic tolerance to MDMA (3,4-methylenedioxymetamphetamine) covers the empirical data on dosage escalation, reduced subjective efficacy and bingeing in recreational Ecstasy users. Novice users generally take a single Ecstasy tablet, regular users typically take 2-3 tablets, whereas the most experienced users may take 10-25 tablets in a single session. Reduced subjective efficacy following repeated usage is typically described, with many users subjectively reporting the development of tolerance. Intensive self-administration or bingeing is often noted by experienced users. This can comprise 'stacking' on several tablets together, and 'boosting' on successive doses over an extended period. Some experienced users snort Ecstasy powder nasally, whereas a small minority inject MDMA. Chronic tolerance and bingeing are statistically linked to higher rates of drug-related psychobiological problems. In terms of underlying mechanisms, neuroadaptive processes are certainly involved, but there is a paucity of evidence on hepatic and behavioural mechanisms. Further studies specifically designed to investigate chronic tolerance, involving low intermittent dose regimens, are required. Most animal research has involved intensive MDMA dosing regimens designed to engender serotonergic neurotoxicity, and this may comprise another underlying mechanism. If distal serotonin axon terminal loss was also developing in recreational users, it may help to explain why reducing subjective efficacy, dosage escalation and increasing psychobiological problems often develop in parallel. In conclusion, there is extensive evidence for chronic pharmacodynamic tolerance to recreational Ecstasy/MDMA, but the underlying mechanisms are currently unclear. Several traditional processes are probably involved, but one of the possible causes is a novel mechanism largely unique to the ring substituted amphetamine derivatives, namely serotonergic neurotoxicity.

  13. Rhabdomyolysis in MDMA intoxication : A rapid and underestimated killer. "clean" Ecstasy, a safe party drug?

    Eede, Herve Vanden; Montenij, Leon J.; Touw, Daan J.; Norris, Elizabeth M.


    Background: Ecstasy is a popular drug among young adults. It is often thought to be safe. The dose of methylenedioxymethamphetamine (MDMA) in a tablet of Ecstasy varies greatly, and there is also a difference in individual response to a dose of MDMA. Objectives: To increase the awareness of potentia

  14. False-positive amphetamine/ecstasy (MDMA/3,4-methylenedioxymethamphetamine) (CEDIA) and ecstasy (MDMA/3,4-methylenedioxymethamphetamine) (DRI) test results with fenofibrate.

    Kaplan, Yusuf Cem; Erol, Almla; Karadaş, Barş


    This case report describes a false-positive amphetamine/ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and ecstasy (MDMA) screen after therapeutic use of antihyperlipidemic drug, fenofibrate. A 60-year-old male patient was admitted to inpatient psychiatry unit with the diagnosis of alcohol dependency. He was prescribed diazepam 30 mg/day, thiamine 300 mg/day, and naltrexone 50 mg/day. He had also been using fenofibrate 267 mg/day for 3 years for hyperlipidemia and trazodone 100 mg/day for 5 months for insomnia. On routine, urine drugs-of-abuse screening amphetamine/MDMA (CEDIA) test was positive for 4 different occasions and MDMA (DRI) test was positive on 5 different occasions. Gas chromatography/mass spectrometry confirmation of the first positive 3 samples were negative for amphetamine and MDMA. After discontinuation of fenofibrate, amphetamine/MDMA, and MDMA immunoassay results turned out to be negative. Caution should be given to interpretation of amphetamine/MDMA (CEDIA) and MDMA (DRI) tests in patients taking fenofibrate. Specific confirmation with a suitable method should be used to prevent erroneous interpretations.

  15. Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

    Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.


    The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

  16. Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users

    L. Reneman; T. Schilt; M.M. de Win; J. Booij; B. Schmand; W. van den Brink; O. Bakker


    Although 3,4-methytenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the tong-term consequences of MDMA-induced 5-HT neurotoxic Lesions on functions in which 5-HT is involved, such as cognitive func

  17. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

    Lamers, CTJ; Ramaekers, JG; Muntjewerff, ND; Sikkema, KL; Samyn, N; Read, NL; Brookhuis, KA; Riedel, WJ


    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, p

  18. Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

    Lamers, CTJ; Ramaekers, JG; Muntjewerff, ND; Sikkema, KL; Samyn, N; Read, NL; Brookhuis, KA; Riedel, WJ


    Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, p

  19. Increased cortisol levels in hair of recent Ecstasy/MDMA users.

    Parrott, A C; Sands, H R; Jones, L; Clow, A; Evans, P; Downey, L A; Stalder, T


    Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; pEcstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed.

  20. The prevalence, intensity, and assessment of craving for MDMA/ecstasy in recreational users.

    Davis, Alan K; Rosenberg, Harold


    This study evaluated the prevalence, intensity, and correlates of craving for MDMA/ecstasy among recreational users employing a new multi-item, self-report questionnaire reflecting experiences of desire, intention to use, and anticipated loss of control. Using a web-based data collection procedure, we recruited MDMA/ecstasy users (n = 240) to rate their agreement with eight craving statements immediately before and immediately following 90 seconds of exposure to either ecstasy-related or control stimuli. Participants then completed questionnaires to measure ecstasy refusal self-efficacy, passionate engagement in ecstasy use, substance use history, and demographic information. Fifty percent of participants indicated some level of agreement with at least two (out of eight) statements indicative of craving and 30% agreed at some level with six or more such statements. The questionnaire used to assess craving was internally consistent, unidimensional, and had excellent one-week test-retest reliability. Craving scores varied as a function of both cue exposure and frequency of ecstasy use, and were significantly associated with ecstasy-related attitudes. Recreational users of MDMA/ecstasy endorse some experiences indicative of craving for this drug, even though only a minority report intense craving following explicit cue exposure.

  1. An in vitro approach to assessing a potential drug interaction between MDMA (ecstasy) and caffeine.

    Downey, C; Daly, F; O'Boyle, K M


    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug which causes long-term neurotoxicity and increased risk of fatality. In rats, MDMA toxicity is exacerbated by co-administration of caffeine. The aim of this study was to investigate whether caffeine altered the effects of MDMA in a battery of in vitro tests selected to model some of the known actions of MDMA in vivo. In cytotoxicity studies, caffeine modestly enhanced the effect of MDMA on neuronal N2a cell viability but not that of liver, intestinal or kidney cells. MDMA inhibited the formation of fluorescent metabolites by CYP2D6≫CYP3A4>CYP1A2 but this was not altered by caffeine. Similarly, the inhibition of synaptosomal [(3)H] 5-HT uptake by MDMA was not affected by the presence of caffeine. Thus, these in vitro tests failed to detect any substantial interaction between caffeine and MDMA, highlighting the difficulty of modelling in vivo drug interactions using in vitro tests. However, the results show that the inhibition of synaptosomal [(3)H] 5-HT uptake by MDMA was greater at 41°C and 25°C than at 37°C which raises the possibility that MDMA's effect on SERT in vivo may be increased as body temperature increases, contributing to its harmful effects in users.

  2. Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells

    Popova, Dina; Forsblad, Andréas; Hashemian, Sanaz; Jacobsson, Stig O. P.


    3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differen...

  3. Mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated mitochondrial dysfunction in rat liver.

    Moon, Kwan-Hoon; Upreti, Vijay V; Yu, Li-Rong; Lee, Insong J; Ye, Xiaoying; Eddington, Natalie D; Veenstra, Timothy D; Song, Byoung-Joon


    Despite numerous reports citing the acute hepatotoxicity caused by 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy), the underlying mechanism of organ damage is poorly understood. We hypothesized that key mitochondrial proteins are oxidatively modified and inactivated in MDMA-exposed tissues. The aim of this study was to identify and investigate the mechanism of inactivation of oxidatively modified mitochondrial proteins, prior to the extensive mitochondrial dysfunction and liver damage following MDMA exposure. MDMA-treated rats showed abnormal liver histology with significant elevation in plasma transaminases, nitric oxide synthase, and the level of hydrogen peroxide. Oxidatively modified mitochondrial proteins in control and MDMA-exposed rats were labeled with biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins, purified with streptavidin-agarose, and resolved using 2-DE. Comparative 2-DE analysis of biotin-NM-labeled proteins revealed markedly increased levels of oxidatively modified proteins following MDMA exposure. Mass spectrometric analysis identified oxidatively modified mitochondrial proteins involved in energy supply, fat metabolism, antioxidant defense, and chaperone activities. Among these, the activities of mitochondrial aldehyde dehydrogenase, 3-ketoacyl-CoA thiolases, and ATP synthase were significantly inhibited following MDMA exposure. Our data show for the first time that MDMA causes the oxidative inactivation of key mitochondrial enzymes which most likely contributes to mitochondrial dysfunction and subsequent liver damage in MDMA-exposed animals.

  4. 'Ecstasy' as a social drug: MDMA preferentially affects responses to emotional stimuli with social content.

    Wardle, Margaret C; Kirkpatrick, Matthew G; de Wit, Harriet


    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is used recreationally to improve mood and sociability, and has generated clinical interest as a possible adjunct to psychotherapy. One way that MDMA may produce positive 'prosocial' effects is by changing responses to emotional stimuli, especially stimuli with social content. Here, we examined for the first time how MDMA affects subjective responses to positive, negative and neutral emotional pictures with and without social content. We hypothesized that MDMA would dose-dependently increase reactivity to positive emotional stimuli and dampen reactivity to negative stimuli, and that these effects would be most pronounced for pictures with people in them. The data were obtained from two studies using similar designs with healthy occasional MDMA users (total N = 101). During each session, participants received MDMA (0, 0.75 and 1.5 mg/kg oral), and then rated their positive and negative responses to standardized positive, negative and neutral pictures with and without social content. MDMA increased positive ratings of positive social pictures, but reduced positive ratings of non-social positive pictures. We speculate this 'socially selective' effect contributes to the prosocial effects of MDMA by increasing the comparative value of social contact and closeness with others. This effect may also contribute to its attractiveness to recreational users.

  5. Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines.

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg


    Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies.

  6. MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users.

    Parrott, Andrew C


    Serotonergic neurotoxicity following MDMA is well-established in laboratory animals, and neuroimaging studies have found lower serotonin transporter (SERT) binding in abstinent Ecstasy/MDMA users. Serotonin is a modulator for many different psychobiological functions, and this review will summarize the evidence for equivalent functional deficits in recreational users. Declarative memory, prospective memory, and higher cognitive skills are often impaired. Neurocognitive deficits are associated with reduced SERT in the hippocampus, parietal cortex, and prefrontal cortex. EEG and ERP studies have shown localised reductions in brain activity during neurocognitive performance. Deficits in sleep, mood, vision, pain, psychomotor skill, tremor, neurohormonal activity, and psychiatric status, have also been demonstrated. The children of mothers who take Ecstasy/MDMA during pregnancy have developmental problems. These psychobiological deficits are wide-ranging, and occur in functions known to be modulated by serotonin. They are often related to lifetime dosage, with light users showing slight changes, and heavy users displaying more pronounced problems. In summary, abstinent Ecstasy/MDMA users can show deficits in a wide range of biobehavioral functions with a serotonergic component.

  7. In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

    Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K;


    Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....

  8. MDMA (Ecstasy) Decreases the Number of Neurons and Stem Cells in Embryonic Cortical Cultures

    Kindlundh-Högberg, Anna M S; Pickering, Chris; Wicher, Grzegorz


    Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated...... CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 muM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 muM) in NeuN-positive cells. By q......PCR, MDMA (200 muM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D(1) receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT(1A) receptor. In conclusion, MDMA caused a marked reduction in stem cells...

  9. The origin of MDMA ("ecstasy")--separating the facts from the myth.

    Bernschneider-Reif, S; Oxler, F; Freudenmann, R W


    MDMA (3,4-methylenedioxy-N-methylamphetamine), better known as "Ecstasy", is a synthetic drug with psychedelic and stimulant effects which has gained great popularity. It is closely tied to the underground scene, but has also been used therapeutically as an adjunct to psychotherapy. Both scientific as well as newspaper articles communicate faulty or incomplete information on the origin of MDMA and the role of the German pharmaceutical-chemical company Merck in its development. One of the most common misconceptions is that the substance was synthesized with the goal of creating an anorectic but was not marketed by Merck because of side effects. It was our aim to clarify the circumstances of MDMA's discovery at Merck. An interdisciplinary working group conducted a comprehensive analysis of the original documents in Merck's historical archive in Darmstadt, Germany. It could be revealed that MDMA was in fact mentioned for the first time in files from 1912, but not under this name. In the lab journals it was called "Methylsafrylamin". In a patent certificate it was mentioned only with its chemical structure. Merck applied for this patent to protect an alternative chemical method for synthesizing the styptic hydrastinine, not appetite suppressants. MDMA was not the key substance in this patent, only a precursor. Archive documents revealed that Merck's scientists did not perform basic pharmacological tests with MDMA (now called "Safrylmethylamin") before 1927. These tests were halted for economic reasons. In the 1950s, primitive toxicological studies were conducted but MDMA was not tested in humans.

  10. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V; Eddington, Natalie D; Lee, Insong J


    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage.

  11. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael


    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects.

  12. Procedural and declarative memory task performance, and the memory consolidation function of sleep, in recent and abstinent ecstasy/MDMA users.

    Blagrove, Mark; Seddon, Jennifer; George, Sophie; Parrott, Andrew C; Stickgold, Robert; Walker, Matthew P; Jones, Katy A; Morgan, Michael J


    Ecstasy/MDMA use has been associated with various memory deficits. This study assessed declarative and procedural memory in ecstasy/MDMA users. Participants were tested in two sessions, 24 h apart, so that the memory consolidation function of sleep on both types of memory could also be assessed. Groups were: drug-naive controls (n = 24); recent ecstasy/MDMA users, who had taken ecstasy/MDMA 2-3 days before the first testing session (n = 25), and abstinent users, who had not taken ecstasy/MDMA for at least 8 days before testing (n = 17). Procedural memory did not differ between groups, but greater lifetime consumption of ecstasy was associated with poorer procedural memory. Recent ecstasy/MDMA users who had taken other drugs (mainly cannabis) 48-24 h before testing exhibited poorer declarative memory than controls, but recent users who had not taken other drugs in this 48-24-h period did not differ from controls. Greater lifetime consumption of ecstasy, and of cocaine, were associated with greater deficits in declarative memory. These results suggest that procedural, as well as declarative, memory deficits are associated with the extent of past ecstasy use. However, ecstasy/MDMA did not affect the memory consolidation function of sleep for either the declarative or the procedural memory task.

  13. A cannabinoid CB(1) receptor antagonist ameliorates impairment of recognition memory on withdrawal from MDMA (Ecstasy).

    Nawata, Yoko; Hiranita, Takato; Yamamoto, Tsuneyuki


    (+/-)-3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') abusers have persistent neuropsychiatric deficits including memory impairments after the cessation of abuse. On the other hand, cannabinoid CB(1) receptors have been implicated in learning/memory, and are highly expressed in the hippocampus, a region of the brain believed to have an important function in certain forms of learning and memory. In this study, we clarified the mechanism underlying the cognitive impairment that develops during MDMA withdrawal from the standpoint of the cannabinoid CB(1) receptors. Mice were administered MDMA (10 mg/kg, i.p.) once a day for 7 days. On the 7th day of withdrawal, a novel object recognition task was performed and the amount of cannabinoid CB(1) receptor protein was measured with western blotting. Recognition performance was impaired on the 7th day of withdrawal. This impairment was blocked by AM251, a cannabinoid CB(1) receptor antagonist, administered 30 min before the training trial or co-administered with MDMA. At this time, the level of cannabinoid CB(1) receptor protein increased significantly in the hippocampus but not the prefrontal cortex or striatum. This increase of CB(1) receptor protein in the hippocampus was also blocked by the co-administration of AM251. Furthermore, CB(1) receptor knockout mice showed no impairment of recognition performance on the withdrawal from MDMA. The impairment of recognition memory during withdrawal from MDMA may result from the activation of cannabinoid CB(1) receptors in the hippocampus.

  14. Behavioral effects and pharmacokinetics of (±)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) after intragastric administration to baboons.

    Goodwin, Amy K; Mueller, Melanie; Shell, Courtney D; Ricaurte, George A; Ator, Nancy A


    (±)-3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.32-7.8 mg/kg) were administered via an intragastric catheter to adult male baboons (N = 4). Effects of MDMA on food-maintained responding were assessed over a 20-hour period, whereas untrained behaviors and fine-motor coordination were characterized every 30 minutes until 3 hours postadministration. Levels of MDMA and metabolites in plasma were measured in the same animals (n = 3) after dosing on a separate occasion. MDMA decreased food-maintained responding over the 20-hour period, and systematic behavioral observations revealed increased frequency of bruxism as the dose of MDMA was increased. Drug blood level determinations showed no MDMA after the lower doses of MDMA tested (0.32-1.0 mg/kg) and modest levels after higher MDMA doses (3.2-7.8 mg/kg). High levels of 3,4-dihydroxymethamphetamine (HHMA) were detected after all doses of MDMA, suggesting extensive first-pass metabolism of MDMA in the baboon. The present results demonstrate that MDMA administered via an intragastric catheter produced behavioral effects that have also been reported in humans. Similar to humans, blood levels of MDMA after oral administration may not be predictive of the behavioral effects of MDMA. Metabolites, particularly HHMA, may play a significant role in the behavioral effects of MDMA.

  15. Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.

    Booij, Linda; Soucy, Jean-Paul; Young, Simon N; Regoli, Martine; Gravel, Paul; Diksic, Mirko; Leyton, Marco; Pihl, Robert O; Benkelfat, Chawki


    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized (11) C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized (11) C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized (11) C-AMT trapping in the brainstem and pre-frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms.

  16. Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart.

    Koczor, Christopher A; Ludlow, Ivan; Hight, Robert S; Jiao, Zhe; Fields, Earl; Ludaway, Tomika; Russ, Rodney; Torres, Rebecca A; Lewis, William


    MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA's acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy. MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10- or 35-day MDMA, or daily 10-day MDMA followed by 25-day saline washout (10 + 25 days). MDMA treatment caused differential gene expression (p 1.5) in 752 genes following 10 days, 558 genes following 35 days, and 113 genes following 10-day MDMA + 25-day saline washout. Changes in MAPK and circadian rhythm gene expression were identified as early as 10 days. After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was found to be 71% at 10 days, 68% at 35 days, and 91% at 10 + 25 days washout. Differential gene expression paralleled DNA methylation in 22% of genes at 10-day treatment, 17% at 35 days, and 48% at 10 + 25 days washout. We show here that MDMA induced cardiac epigenetic changes in DNA methylation where hypermethylation predominated. Moreover, MDMA induced gene expression of key elements of circadian rhythm regulatory genes. This suggests a fundamental organism-level event to explain some of the etiologies of MDMA dysfunction in the heart.

  17. Searching the Internet for drug-related web sites: analysis of online available information on ecstasy (MDMA).

    Deluca, Paolo; Schifano, Fabrizio


    Although the Internet is a growing source of information on MDMA/ecstasy, no studies so far have investigated the level and quality of ecstasy information available to the typical Web user. In the present study, 280 Web sites were identified and analyzed; 50.4% had an anti-drug approach, 16.2% a harm reduction approach, and 24.8% a pro-drug approach. MDMA pro-drug Web sites appeared significantly earlier in the search engines' results list than both anti-drug and harm reduction Web sites (F (3; 159) = 3.288; p = .022). This study represents the first systematic analysis of information available online on ecstasy. Implications for further research are discussed.

  18. Detection of "bath salts" and other novel psychoactive substances in hair samples of ecstasy/MDMA/"Molly" users.

    Palamar, Joseph J; Salomone, Alberto; Vincenti, Marco; Cleland, Charles M


    Ecstasy (MDMA) in the US is commonly adulterated with other drugs, but research has not focused on purity of ecstasy since the phenomenon of "Molly" (ecstasy marketed as pure MDMA) arose in the US. We piloted a rapid electronic survey in 2015 to assess use of novel psychoactive substances (NPS) and other drugs among 679 nightclub/festival-attending young adults (age 18-25) in New York City. A quarter (26.1%) of the sample provided a hair sample to be analyzed for the presence of select synthetic cathinones ("bath salts") and some other NPS. Samples were analyzed using fully validated UHPLC-MS/MS methods. To examine consistency of self-report, analyses focused on the 48 participants with an analyzable hair sample who reported lifetime ecstasy/MDMA/Molly use. Half (50.0%) of the hair samples contained MDMA, 47.9% contained butylone, and 10.4% contained methylone. Of those who reported no lifetime use of "bath salts", stimulant NPS, or unknown pills or powders, about four out of ten (41.2%) tested positive for butylone, methylone, alpha-PVP, 5/6-APB, or 4-FA. Racial minorities were more likely to test positive for butylone or test positive for NPS after reporting no lifetime use. Frequent nightclub/festival attendance was the strongest predictor of testing positive for MDMA, butylone, or methylone. Results suggest that many ecstasy-using nightclub/festival attendees may be unintentionally using "bath salts" or other NPS. Prevention and harm reduction education is needed for this population and "drug checking" (e.g., pill testing) may be beneficial for those rejecting abstinence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Anticataleptic activity of cathinone and MDMA (Ecstasy) upon acute and subchronic administration in rat.

    Banjaw, Mehret Yerdaw; Mayerhofer, Andreas; Schmidt, Werner J


    It was recently demonstrated that acute administration of 3,4-methylenedioxymethamphet-amine (MDMA, "Ecstasy") is capable of counteracting haloperidol-induced catalepsy in rats. The present study was done with another psychostimulant, S-(-)-cathinone. In these experiments, 32 male Sprague-Dawley rats, 225 +/- 25 g, were used. They were divided into three groups. All groups received 0.5 mg/kg haloperidol in normal saline (s.c.) as a first injection. Then 30 min later each group received either isotonic phosphate-buffered saline, 1 mg/kg S-(-)-cathinone, or 2.5 mg/kg (RS)-MDMA (s.c.) as a second injection. The results of descent latency on both the horizontal bar and vertical grid showed that S-(-)-cathinone or (RS)-MDMA upon acute administration induces a strong anticataleptic activity (P mechanism of the observed strong anticataleptic activity of S-(-)-cathinone (which is considered a potent dopamine releaser) requires further investigation.

  20. High ambient temperature increases 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")-induced Fos expression in a region-specific manner.

    Hargreaves, G A; Hunt, G E; Cornish, J L; McGregor, I S


    3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug that is often taken under hot conditions at dance clubs. High ambient temperature increases MDMA-induced hyperthermia and recent studies suggest that high temperatures may also enhance the rewarding and prosocial effects of MDMA in rats. The present study investigated whether ambient temperature influences MDMA-induced expression of Fos, a marker of neural activation. Male Wistar rats received either MDMA (10 mg/kg i.p.) or saline, and were placed in test chambers for 2 h at either 19 or 30 degrees C. MDMA caused significant hyperthermia at 30 degrees C and a modest hypothermia at 19 degrees C. The 30 degrees C ambient temperature had little effect on Fos expression in vehicle-treated rats. However MDMA-induced Fos expression was augmented in 15 of 30 brain regions at the high temperature. These regions included (1) sites associated with thermoregulation such as the median preoptic nucleus, dorsomedial hypothalamus and raphe pallidus, (2) the supraoptic nucleus, a region important for osmoregulation and a key mediator of oxytocin and vasopressin release, (3) the medial and central nuclei of the amygdala, important in the regulation of social and emotional behaviors, and (4) the shell of the nucleus accumbens and (anterior) ventral tegmental area, regions associated with the reinforcing effects of MDMA. MDMA-induced Fos expression was unaffected by ambient temperature at many other sites, and was diminished at high temperature at one site (the islands of Calleja), suggesting that the effect of temperature on MDMA-induced Fos expression was not a general pharmacokinetic effect. Overall, these results indicate that high temperatures accentuate key neural effects of MDMA and this may help explain the widespread use of the drug under hot conditions at dance parties as well as the more hazardous nature of MDMA taken under such conditions.

  1. Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells.

    Popova, Dina; Forsblad, Andréas; Hashemian, Sanaz; Jacobsson, Stig O P


    3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT), that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A). The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm) in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.

  2. Chronic exposure to MDMA (Ecstasy elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

    Swann Alan C


    Full Text Available Abstract Background The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA. Methods The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg and a saline control group (N = 9/group. All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13. Rats were then given an additional 25-day washout period, and re-challenged (day 38 with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39. Open-field locomotor activity was recorded using a computerized automated activity monitoring system. Results Acute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group, while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change

  3. Duloxetine inhibits effects of MDMA ("ecstasy" in vitro and in humans in a randomized placebo-controlled laboratory study.

    Cédric M Hysek

    Full Text Available UNLABELLED: This study assessed the effects of the serotonin (5-HT and norepinephrine (NE transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence. TRIAL REGISTRATION: NCT00990067.

  4. Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") are attenuated by the serotonin uptake inhibitor citalopram.

    Liechti, M E; Baumann, C; Gamma, A; Vollenweider, F X


    3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo-controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies.

  5. Constructing the ecstasy of MDMA from its component mental organs: Proposing the primer/probe method.

    Ray, Thomas S


    The drug MDMA, commonly known as ecstasy, produces a specific and distinct open hearted mental state, which led to the creation of a new pharmacological class, "entactogens". Extensive literature on its mechanisms of action has come to characterize MDMA as a "messy" drug with multiple mechanisms, but the consensus is that the distinctive entactogenic effects arise from the release of neurotransmitters, primarily serotonin. I propose an alternative hypothesis: The entactogenic mental state is due to the simultaneous direct activation of imidazoline-1 (I1) and serotonin-2 (5-HT2) receptors by MDMA. This hypothesis emerges from "mental organ" theory, which embodies many hypotheses, the most relevant of which are: "Mental organs" are populations of neurons that all express their defining metabotropic receptor, and each mental organ plays a distinct role in the mind, a role shaped by evolution as mental organs evolve by duplication and divergence. Mental organs are the mechanism by which evolution sculpts the mind. Mental organs can be in or out of consciousness. In order for a mental organ to enter consciousness, three things must happen: The mental organ must be activated directly at its defining receptor. 5-HT2 must be simultaneously activated. One of the functions of activated 5-HT2 is to load other simultaneously activated mental organs fully into consciousness. In some cases THC must be introduced to remove long-term blocks mediated by the cannabinoid system. I propose the "primer/probe" method to test these hypotheses. A "primer" is a drug that selectively activates 5-HT2 (e.g. DOB or MEM) or serotonin-1 (5-HT1) and 5-HT2 (e.g. DOET or 2C-B-fly). A "probe" is a drug that activates a receptor whose corresponding mental organ we wish to load into consciousness in order to understand its role in the mind. The mental organ is loaded into consciousness when the primer and probe are taken together, but not when taken separately. For example, the blood pressure

  6. Ecstasy (MDMA and its effects on kidneys and their treatment: a review

    Feyza Bora


    Full Text Available Ecstasy (MDMA; 3,4-methylenedioxymethylamphetamine is an illicit drug that has been increasingly abused by young people. Its effects include euphoria, enhanced sociability and heightened mental awareness. These come about via the increase of serotonin in both the central nervous system and the sympathetic nervous system. Despite the drug’s prevalent abuse, serious or adverse effects are rare. Due to personal pharmacokinetics, effects from the same dosage vary according to the individual. Fatal instances may include acute hyponatremia, hyperthermia (>42 °C, disseminated intravascular coagulation (DIC resulting from hyperthermia affecting the kidneys, and non-traumatic rhabdomyolysis. However, it is seldom the case that hyponatremia and hyperthermia co-exist. Hyponatremia is thought to be caused by HMMA – a metabolite of MDMA. Hyponatremia is caused by the inappropriate secretion of arginine vasopressin (AVP and the excessive intake of hypotonic liquid accompanied by increased hyperthermia. Symptomatic, even deadly hyponatremia is seen more frequently in females, with the effects of oestrogen on arginine vasopressin believed to be the cause. Onset in such cases is acute, and treatment should be given to symptomatic patients as quickly as possible, with 3% saline administered when necessary. Reasons for acute kidney injury may include rhabdomyolysis, malign hypertension, and necrotizing vasculitis.

  7. Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or 'ecstasy' and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices.

    Kamboj, Sunjeev K; Kilford, Emma J; Minchin, Stephanie; Moss, Abigail; Lawn, Will; Das, Ravi K; Falconer, Caroline J; Gilbert, Paul; Curran, H Valerie; Freeman, Tom P


    3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA's neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously.

  8. A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

    Orio, Laura; Llopis, Noemi; Torres, Elisa; Izco, Maria; O'Shea, Esther; Colado, M Isabel


    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling.

  9. Dorsal hippocampal NMDA receptors mediate the interactive effects of arachidonylcyclopropylamide and MDMA/ecstasy on memory retrieval in rats.

    Ghaderi, Marzieh; Rezayof, Ameneh; Vousooghi, Nasim; Zarrindast, Mohammad-Reza


    A combination of cannabis and ecstasy may change the cognitive functions more than either drug alone. The present study was designed to investigate the possible involvement of dorsal hippocampal NMDA receptors in the interactive effects of arachidonylcyclopropylamide (ACPA) and ecstasy/MDMA on memory retrieval. Adult male Wistar rats were cannulated into the CA1 regions of the dorsal hippocampus (intra-CA1) and memory retrieval was examined using the step-through type of passive avoidance task. Intra-CA1 microinjection of a selective CB1 receptor agonist, ACPA (0.5-4ng/rat) immediately before the testing phase (pre-test), but not after the training phase (post-training), impaired memory retrieval. In addition, pre-test intra-CA1 microinjection of MDMA (0.5-1μg/rat) dose-dependently decreased step-through latency, indicating an amnesic effect of the drug by itself. Interestingly, pre-test microinjection of a higher dose of MDMA into the CA1 regions significantly improved ACPA-induced memory impairment. Moreover, pre-test intra-CA1 microinjection of a selective NMDA receptor antagonist, D-AP5 (1 and 2μg/rat) inhibited the reversal effect of MDMA on the impairment of memory retrieval induced by ACPA. Pre-test intra-CA1 microinjection of the same doses of D-AP5 had no effect on memory retrieval alone. These findings suggest that ACPA or MDMA consumption can induce memory retrieval impairment, while their co-administration improves this amnesic effect through interacting with hippocampal glutamatergic-NMDA receptor mechanism. Thus, it seems that the tendency to abuse cannabis with ecstasy may be for avoiding cognitive dysfunction.

  10. Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical and cholinergic input in PC12 cells.

    Hondebrink, Laura; Meulenbelt, Jan; Rietjens, Saskia J; Meijer, Marieke; Westerink, Remco H S


    Reversal of the dopamine (DA) membrane transporter is the main mechanism through which many drugs of abuse increase DA levels. However, drug-induced modulation of exocytotic DA release by electrical (depolarization) and neurochemical inputs (e.g., acetylcholine (ACh)) may also contribute. We therefore investigated effects of methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP) (1-1000 μM) on these inputs by measuring drug-induced changes in basal, depolarization- and ACh-evoked intracellular calcium concentrations ([Ca(2+)](i)) using a dopaminergic model (PC12 cells) and Fura 2 calcium imaging. The strongest drug-induced effects were observed on cholinergic input. At 0.1mM all drugs inhibited the ACh-evoked [Ca(2+)](i) increases by 40-75%, whereas ACh-evoked [Ca(2+)](i) increases were nearly abolished following higher drug exposure (1mM, 80-97% inhibition). Additionally, high MDMA and mCPP concentrations increased basal [Ca(2+)](i), but only following prior stimulation with ACh. Interestingly, low concentrations of methamphetamine or amphetamine (10 μM) potentiated ACh-evoked [Ca(2+)](i) increases. Depolarization-evoked [Ca(2+)](i) increases were also inhibited following exposure to high drug concentrations, although drugs were less potent on this endpoint. Our data demonstrate that at high drug concentrations all tested drugs reduce stimulation-evoked increases in [Ca(2+)](i), thereby probably reducing dopaminergic output through inhibition of electrical and cholinergic input. Furthermore, the increases in basal [Ca(2+)](i) at high concentrations of MDMA and mCPP likely increases dopaminergic output. Similarly, the increases in ACh-evoked [Ca(2+)](i) upon cholinergic stimulation following exposure to low concentrations of amphetamines can contribute to drug-induced increases in DA levels observed in vivo. Finally, this study shows that mCPP, which is regularly found in

  11. Effects of alcohol (BAC 0.5‰) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety.

    Veldstra, Janet L; Brookhuis, Karel A; de Waard, Dick; Molmans, Barbara H W; Verstraete, Alain G; Skopp, Gisela; Jantos, Ricarda


    An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are relatively rare. The present study was designed to establish the extent of driver impairment as a consequence of ecstasy or combined ecstasy and alcohol use as compared to driving under the influence of 0.3‰, 0.5‰ and 0.8‰ alcohol. Furthermore, subjective performance was also assessed. Alcohol and ecstasy mainly influenced automated driving performance such as lateral and speed control. However, small to no effects of the substances were found on more complex driving behaviour. Overall, variance within the different driving measures was high especially when participants were treated with 3.4-methylenedioxy-methamphetamine (MDMA) and alcohol. Furthermore, equivalence testing showed that combined use may lead to impaired driving for some, but not all, drivers. Participants rated their own performance to be slightly worse than normal in both studies. Since driving was actually seriously deteriorated, this was a falsely positive assessment of their condition. The dissociation between subjective perceptions and objective performance decrements are important notions for traffic safety since this may affect a driver's judgement of whether or not it is safe to drive. For example, an intoxicated individual might decide to drive because the feelings of alertness caused by MDMA cloud the impairing effects of other drugs such as alcohol, thereby creating a potentially serious risk for traffic safety.

  12. Reduced 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-initiated oxidative DNA damage and neurodegeneration in prostaglandin H synthase-1 knockout mice.

    Jeng, Winnie; Wells, Peter G


    The neurodegenerative potential of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and underlying mechanisms are under debate. Here, we show that MDMA is a substrate for CNS prostaglandin H synthase (PHS)-catalyzed bioactivation to a free radical intermediate that causes reactive oxygen species (ROS) formation and neurodegenerative oxidative DNA damage. In vitro PHS-1-catalyzed bioactivation of MDMA stereoselectively produced free radical intermediate formation and oxidative DNA damage that was blocked by the PHS inhibitor eicosatetraynoic acid. In vivo, MDMA stereoselectively caused gender-independent DNA oxidation and dopaminergic nerve terminal degeneration in several brain regions, dependent on regional PHS-1 levels. Conversely, MDMA-initiated striatal DNA oxidation, nerve terminal degeneration, and motor coordination deficits were reduced in PHS-1 +/- and -/- knockout mice in a gene dose-dependent fashion. These results confirm the neurodegenerative potential of MDMA and provide the first direct evidence for a novel molecular mechanism involving PHS-catalyzed formation of a neurotoxic MDMA free radical intermediate.

  13. N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy').

    Baumann, Michael H; Clark, Robert D; Budzynski, Allison G; Partilla, John S; Blough, Bruce E; Rothman, Richard B


    3,4-Methylenedioxymethamphetamine (MDMA, or 'Ecstasy') is an illicit drug that stimulates the release of serotonin (5-HT) and dopamine (DA) from neurons. Recent evidence reveals that drug users are ingesting piperazine analogs, like 1-benzylpiperazine (BZP, or 'A2') and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, or 'Molly'), to mimic psychoactive effects of MDMA. In the present study, we compared the neurochemistry of MDMA, BZP, and TFMPP in rats. The effects of MDMA, BZP, and TFMPP on transporter-mediated efflux of [3H]5-HT and [3H]MPP+ (DA transporter substrate) were determined in synaptosomes. The effects of drugs on extracellular levels of 5-HT and DA were examined using in vivo microdialysis in conscious rats. MDMA evoked transporter-mediated release of [3H]5-HT and [3H]MPP+. BZP released [3H]MPP+, whereas TFMPP was a selective releaser of [3H]5-HT. MDMA (1-3 mg/kg, i.v.) increased dialysate 5-HT and DA in a dose-related fashion, with actions on 5-HT being predominant. BZP (3-10 mg/kg, i.v.) elevated dialysate DA and 5-HT, while TFMPP (3-10 mg/kg, i.v.) elevated 5-HT. Administration of BZP plus TFMPP at a 1:1 ratio (BZP/TFMPP) produced parallel increases in dialysate 5-HT and DA; a 3 mg/kg dose of BZP/TFMPP mirrored the effects of MDMA. At a 10 mg/kg dose, BZP/TFMPP increased dialysate DA more than the summed effects of each drug alone, and some rats developed seizures. Our results show that BZP/TFMPP and MDMA share the ability to evoke monoamine release, but dangerous drug-drug synergism may occur when piperazines are coadministered at high doses.

  14. Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use.

    Kiyatkin, Eugene A; Kim, Albert H; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin


    MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22-23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ~1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues.

  15. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine.

    Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H; Montgomery, Therese


    Amphetamine ('Speed'), methamphetamine ('Ice') and its congener 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity.

  16. Distribution of temperature changes and neurovascular coupling in rat brain following 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") exposure.

    Coman, Daniel; Sanganahalli, Basavaraju G; Jiang, Lihong; Hyder, Fahmeed; Behar, Kevin L


    (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an abused psychostimulant that produces strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP-3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA(4-))). The MDMA-induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA-induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions

  17. Using the Theory of Planned Behavior to predict implementation of harm reduction strategies among MDMA/ecstasy users.

    Davis, Alan K; Rosenberg, Harold


    This prospective study was designed to test whether the variables proposed by the Theory of Planned Behavior (TPB) were associated with baseline intention to implement and subsequent use of 2 MDMA/ecstasy-specific harm reduction interventions: preloading/postloading and pill testing/pill checking. Using targeted Facebook advertisements, an international sample of 391 recreational ecstasy users were recruited to complete questionnaires assessing their ecstasy consumption history, and their attitudes, subjective norms, perceived behavioral control, habit strength (past strategy use), and intention to use these two strategies. Attitudes, subjective norms, and perceived behavioral control were significantly associated with baseline intention to preload/postload and pill test/pill check. Out of the 391 baseline participants, 100 completed the two-month follow-up assessment. Baseline habit strength and frequency of ecstasy consumption during the three months prior to baseline were the only significant predictors of how often participants used the preloading/postloading strategy during the follow-up. Baseline intention to pill test/pill check was the only significant predictor of how often participants used this strategy during the follow-up. These findings provide partial support for TPB variables as both correlates of baseline intention to implement and predictors of subsequent use of these two strategies. Future investigations could assess whether factors related to ecstasy consumption (e.g., subjective level of intoxication, craving, negative consequences following consumption), and environmental factors (e.g., accessibility and availability of harm reduction resources) improve the prediction of how often ecstasy users employ these and other harm reduction strategies. (PsycINFO Database Record

  18. Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy in anxiety-like responses in mice

    V. Ferraz-de-Paula


    Full Text Available Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group. The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05 effects: a a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e increased serum corticosterone levels, and f increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

  19. Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

    Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan


    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history.

  20. Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine

    Ball, Kevin T.; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan


    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one’s drug use history. PMID:26241170

  1. Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model.

    Cerretani, Daniela; Riezzo, Irene; Fiaschi, Anna Ida; Centini, Fabio; Giorgi, Giorgio; D'Errico, Stefano; Fiore, Carmela; Karch, Steven B; Neri, Margherita; Pomara, Cristoforo; Turillazzi, Emanuela; Fineschi, Vittorio


    Experimental and clinical data indicate that 3,4-methylenedioxy-N-methylamphetamine (MDMA) abuse can produce significant cardiovascular toxicity. A mechanism may be a direct toxic effect of redox active metabolites of MDMA. To evaluate the effect of a single MDMA dose on cellular antioxidant defence system and to investigate the morphology in male albino rats, total glutathione (GSH), oxidised glutathione (GSSG), ascorbic acid (AA), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and malondialdehyde (MDAL) were studied. The effects were evaluated at 3, 6, 16 and 24 h after MDMA administration. Antioxidant enzymes activity was significantly reduced: GPx (-24%) and SOD (-50%) after 3 h and GR (-19%) after 6 h from treatment. AA levels decrease (-37%) after 3 h and (-30%) after 6 h; MDAL level increased (+119%) after 3 h; GSH levels decreased after 3 (31.3%) and 6 h (37.9%) from MDMA treatment. GSSG content was not affected by ecstasy administration. Myocardial contraction band necrosis (CBN) was already visible in rats killed at 6 h. After 16 h, macrophagic monocytes around the necrotic myocardial cells were observed, and within 24 h, this infiltrate became more widespread with an early removal of the necrotic material. Calcium deposits were observed within ventricular cardiomyocytes with intact nuclei and sarcomeres. Single administration of MDMA can significantly alter the cellular antioxidant defence system and produce oxidative stress which may result in lipid peroxidation and disruption of Ca(2 +) homeostasis. The depression in Ca(2+) regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca(2 +) overload, CBN and cell death.

  2. Exploring functional data analysis and wavelet principal component analysis on ecstasy (MDMA wastewater data

    Stefania Salvatore


    Full Text Available Abstract Background Wastewater-based epidemiology (WBE is a novel approach in drug use epidemiology which aims to monitor the extent of use of various drugs in a community. In this study, we investigate functional principal component analysis (FPCA as a tool for analysing WBE data and compare it to traditional principal component analysis (PCA and to wavelet principal component analysis (WPCA which is more flexible temporally. Methods We analysed temporal wastewater data from 42 European cities collected daily over one week in March 2013. The main temporal features of ecstasy (MDMA were extracted using FPCA using both Fourier and B-spline basis functions with three different smoothing parameters, along with PCA and WPCA with different mother wavelets and shrinkage rules. The stability of FPCA was explored through bootstrapping and analysis of sensitivity to missing data. Results The first three principal components (PCs, functional principal components (FPCs and wavelet principal components (WPCs explained 87.5-99.6 % of the temporal variation between cities, depending on the choice of basis and smoothing. The extracted temporal features from PCA, FPCA and WPCA were consistent. FPCA using Fourier basis and common-optimal smoothing was the most stable and least sensitive to missing data. Conclusion FPCA is a flexible and analytically tractable method for analysing temporal changes in wastewater data, and is robust to missing data. WPCA did not reveal any rapid temporal changes in the data not captured by FPCA. Overall the results suggest FPCA with Fourier basis functions and common-optimal smoothing parameter as the most accurate approach when analysing WBE data.

  3. Effects of MDMA (ecstasy), and multiple drugs use on (simulated) driving performance and traffic safety

    Brookhuis, KA; de Waard, D; Samyn, N


    Rationale. The effects of MDMA on driving behaviour are not clear, since the direct effects of MDMA on cognitive performance are reported as not generally negative. Objectives. To assess in an advanced driving simulator acute effects on simulated driving behaviour and heart rate of MDMA, and effects

  4. Short- and long-term effects of MDMA ("ecstasy") on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo.

    Bogen, Inger Lise; Haug, Kristin Huse; Myhre, Oddvar; Fonnum, Frode


    3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a commonly abused drug which has been shown to be neurotoxic to serotonergic neurons in many species. The exact mechanism responsible for the neurotoxicity of MDMA is, however, poorly understood. In this study, the effects of MDMA on the synaptosomal and vesicular uptake of neurotransmitters were investigated. Our results show that MDMA (0.5-20 microM) reduces both synaptosomal and vesicular uptake of serotonin and dopamine in a dose dependent manner in vitro, while the uptake of glutamate and gamma-aminobutyric acid (GABA) remains unaffected. Ex vivo experiments support the importance of the monoamines, with predominant dopaminergic inhibition at short-term exposure (3 x 15 mg/kg; 2-h intervals), and exclusively serotonergic inhibition at long-term exposure (2 x 10 mg/kg per day; 4 days). This study also compares MDMA and the structurally related antidepressant paroxetine, in an attempt to reveal possible cellular mechanisms for the serotonergic toxicity of MDMA. One important difference between paroxetine and MDMA is that only MDMA has the capability of inhibiting vesicular uptake of monoamines at doses used. We suggest that inhibition of the vesicular monoamine transporter-2, and a following increase in cytoplasmatic monoamine concentrations, might be crucial for the neurotoxic effect of MDMA.

  5. Application of the Passionate Attachment Model to Recreational Use of MDMA/Ecstasy.

    Davis, Alan K; Rosenberg, Harold


    Those who are not addicted to ecstasy, but who use it persistently over time, could be viewed as having a "passionate attachment" to a highly valued activity. To evaluate the associations of obsessive and harmonious passion with psychological and behavioral aspects of ecstasy consumption, we recruited a community sample of ecstasy users to complete a modified version of the Passion Scale (Vallerand et al. 2003) and other questionnaires assessing their substance use history, self-efficacy to refuse ecstasy, and use of ecstasy to cope with worries and problems. Both Obsessive and Harmonious passion scores were negatively correlated with self-efficacy to refuse ecstasy and positively correlated with using ecstasy to cope with worries and problems. The findings also provided partial support for our hypotheses that scores on the Obsessive Passion subscale would be associated with number of times participants had used ecstasy, the frequency of use, and the typical number of pills consumed. Participants agreed more strongly with statements indicative of Harmonious Passion to consume ecstasy, but Harmonious subscale scores were not associated with several measures of consumption. As a supplemental measure, the modified questionnaire could provide a more comprehensive picture of the psychology of one's ecstasy use.

  6. Detection of “Bath Salts” and Other Novel Psychoactive Substances in Hair Samples of Ecstasy/MDMA/“Molly” Users

    Palamar, Joseph J.; Salomone, Alberto; Vincenti, Marco; Cleland, Charles M.


    Background Ecstasy (MDMA) in the US is commonly adulterated with other drugs, but research has not focused on purity of ecstasy since the phenomenon of “Molly” (ecstasy marketed as pure MDMA) arose in the US. Methods We piloted a rapid electronic survey in 2015 to assess use of novel psychoactive substances (NPS) and other drugs among 679 nightclub/festival-attending young adults (age 18–25) in New York City. A quarter (26.1%) of the sample provided a hair sample to be analyzed for the presence of select synthetic cathinones (“bath salts”) and some other NPS. Samples were analyzed using fully validated UHPLC-MS/MS methods. To examine consistency of self-report, analyses focused on the 48 participants with an analyzable hair sample who reported lifetime ecstasy/MDMA/Molly use. Results Half (50.0%) of the hair samples contained MDMA, 47.9% contained butylone, and 10.4% contained methylone. Of those who reported no lifetime use of “bath salts”, stimulant NPS, or unknown pills or powders, about four out of ten (41.2%) tested positive for butylone, methylone, alpha-PVP, 5/6-APB, or 4-FA. Racial minorities were more likely to test positive for butylone or test positive for NPS after reporting no lifetime use. Frequent nightclub/festival attendance was the strongest predictor of testing positive for MDMA, butylone, or methylone. Discussion Results suggest that many ecstasy-using nightclub/festival attendees may be unintentionally using “bath salts” or other NPS. Prevention and harm reduction education is needed for this population and “drug checking” (e.g., pill testing) may be beneficial for those rejecting abstinence. PMID:26883685

  7. Validação de método para determinação de 3,4-metilenodioximetanfetamina (MDMA em comprimidos de ecstasy por cromatografia em fase gasosa Validation of a gas-chromatographic method for the determination of 3,4-methylenedioxymethamphetamine(MDMA in ecstasy tablets

    Silvio Fernandes Lapachinske


    Full Text Available O ecstasy é comercializado, de maneira ilegal, normalmente sob a forma de comprimidos, com cores, aspectos, dimensões e logotipos variados. Quimicamente, é a metilenodioximetanfetamina (MDMA, um composto sintético com propriedades estimulante central e alucinogênicas. Devido à grande expansão do abuso de ecstasy, também tem aumentado o número de casos de intoxicações, decorrentes diretamente da droga (MDMA e análogas e/ou de eventuais adulterantes. Algumas substâncias análogas à MDMA, já identificadas em comprimidos de ecstasy são: metilenodioxietilanfetamina (MDEA, metilenodioxianfetamina (MDA, metanfetamina e anfetamina. Como possíveis adulterantes, geralmente são encontradas cafeína e efedrinas. O objetivo deste trabalho foi a validação de um método analítico para quantificar a MDMA em comprimidos ou cápsulas de ecstasy, através da cromatografia em fase gasosa com detector de nitrogênio/fósforo (GC/NPD. Além disso, substâncias análogas à MDMA e adulterantes também foram identificados. O método, que consiste na dissolução direta da amostra em metanol, centrifugação e diluição do sobrenadante, demonstrou ser simples, rápido e eficiente. Os limites de detecção e quantificação para a MDMA foram respectivamente de 1,5 e 3,0 mg/100 mg de comprimido. Amostras de comprimidos e cápsulas apreendidos como sendo ecstasy provenientes de 25 lotes foram analisadas, apresentando considerável variabilidade na composição e na quantidade de MDMA.Ecstasy is illegally commercialized in the form of tablets with different aspects, colors, sizes, and logotypes. Chemically, ecstasy is 3,4-methylenedioxymethamphetamine (MDMA, a synthetic compound with stimulant and hallucinogenic proprieties. Due to the great expansion of ecstasy abuse, the number of cases of intoxications by MDMA, analogs and eventual adulterant compounds has also increased. Some MDMA analog substances, such as 3,4-methylenedioxyethylamphetamine (MDEA

  8. A PET study of effects of chronic 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on serotonin markers in Göttingen minipig brain

    Cumming, Paul; Møller, Mette; Benda, Kjeld;


    The psychostimulant 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive and neuroch......The psychostimulant 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive...... with MDMA (i.m.), administered at a range of doses. In parallel PET studies, [(11)C]WAY-100635 was used to map the distribution of serotonin 5HT(1A) receptors. The acute MDMA treatment in awake pigs evoked 1 degrees C of hyperthermia. MDMA at total doses greater than 20 mg/kg administered over 2-4 days...... reduced the binding potential (pB) of [(11)C]DASB for serotonin transporters in porcine brain. A mean total dose of 42 mg/kg MDMA in four animals evoked a mean 32% decrease in [(11)C]DASB pB in mesencephalon and diencephalon, and a mean 53% decrease in telencephalic structures. However, this depletion...

  9. Ecstasy (MDMA: effects and patterns of use reported by users in São Paulo

    Almeida Stella Pereira de


    Full Text Available OBJECTIVE: As there are no studies about the use of ecstasy in Brazil, our aim was to identify the effects and patterns of use of this substance among users in the city of São Paulo. METHODS: Subjects were recruited through the snowball technique. Fifty-two subjects of both genders who had been using ecstasy frequently and recently were interviewed. The instrument was a self-reported and anonymous questionnaire. RESULTS: The sample's mean age was 24 years, mostly composed by single, college graduated middle-class subjects. Among the interviewed users, 61.6% used ecstasy at least once per week and 50% of them took one pill per episode of use and 46% more than one. Drug taking was usually performed in company of several people (63% in contexts related to night leisure, such as rave parties (78.8%, dancing clubs (69.2% and parties (53.8%. Ecstasy pills were mainly purchased from friends or acquaintances in order to favor a dancing mood in those places. Most subjects used ecstasy associated to other psychoactive drugs (93.3%, mainly Cannabis, followed by tobacco and LSD. The effects attributed to ecstasy were mainly positive. DISCUSSION: The use of ecstasy in São Paulo has had a recreational pattern quite similar to those described in previous studies. The assessment of the use of ecstasy as positive also agrees with the findings of the literature.

  10. In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin(2A) Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and Hallucinogen Users

    Erritzoe, David; Frokjaer, Vibe G.; Holst, Klaus K.;


    Context: Both hallucinogens and 3,4-methylenedioxy-methamphetamine( MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Objective: To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin(2A) receptor binding.Design: A positron emission tomography study of 24 young adult drug users and 21 nonusing control participants performed with carbon 11 (C-11)-labeled 3-amino-4-[2-[(di......(methyl) amino) methyl] phenyl]sulfanylbenzonitrile (DASB) and fluorine 18 (F-18)-labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n=10) and MDMA-preferring users (n=14...

  11. The impact of recreational MDMA 'ecstasy' use on global form processing.

    White, Claire; Edwards, Mark; Brown, John; Bell, Jason


    The ability to integrate local orientation information into a global form percept was investigated in long-term ecstasy users. Evidence suggests that ecstasy disrupts the serotonin system, with the visual areas of the brain being particularly susceptible. Previous research has found altered orientation processing in the primary visual area (V1) of users, thought to be due to disrupted serotonin-mediated lateral inhibition. The current study aimed to investigate whether orientation deficits extend to higher visual areas involved in global form processing. Forty-five participants completed a psychophysical (Glass pattern) study allowing an investigation into the mechanisms underlying global form processing and sensitivity to changes in the offset of the stimuli (jitter). A subgroup of polydrug-ecstasy users (n=6) with high ecstasy use had significantly higher thresholds for the detection of Glass patterns than controls (n=21, p=0.039) after Bonferroni correction. There was also a significant interaction between jitter level and drug-group, with polydrug-ecstasy users showing reduced sensitivity to alterations in jitter level (p=0.003). These results extend previous research, suggesting disrupted global form processing and reduced sensitivity to orientation jitter with ecstasy use. Further research is needed to investigate this finding in a larger sample of heavy ecstasy users and to differentiate the effects of other drugs.

  12. Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica Ecstasy (MDMA): pharmacological and toxic effects, mechanism of action and clinical management

    Caroline Addison Carvalho Xavier; Patrícia Leal Dantas Lobo; Marta Maria de França Fonteles; Silvânia Maria Mendes de Vasconcelos; Glauce Socorro de Barros Viana; Francisca Cléa Florenço de Sousa


    CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase) é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermé...

  13. Changes in CYP1A2 activity in humans after 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) administration using caffeine as a probe drug.

    Yubero-Lahoz, Samanta; Pardo, Ricardo; Farre, Magí; Mathuna, Brian Ó; Torrens, Marta; Mustata, Cristina; Perez-Mañá, Clara; Langohr, Klaus; Carbó, Marcel Lí; de la Torre, Rafael


    3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 in a previous study, the aim of this work was to study in humans the activity of CYP1A2 in vivo after CYP2D6 had been inhibited by MDMA, using caffeine as a probe drug. Twelve male and nine female recreational MDMA users were included. In session 1, 100 mg of caffeine was given at 0 h. In session 2, a 1.5 mg/kg MDMA dose (range 75-100 mg) was given at 0 h followed by a 100 mg dose of caffeine 4 h later. Aliquots of plasma were assayed for caffeine (137X) and paraxanthine (17X) and statistically significant differences were assessed with a one-way ANOVA. There were significant gender differences at basal condition, which persisted after MDMA administration. CYP1A2 activity was higher in both genders after drug administration, with an increase in 40% in females and 20% in males. Results show an increase in CYP1A2 activity when CYP2D6 is inhibited by MDMA in both genders, being more pronounced in females.

  14. 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice.

    Ferraz-de-Paula, V; Ribeiro, A; Souza-Queiroz, J; Pinheiro, M L; Vecina, J F; Souza, D P M; Quinteiro-Filho, W M; Moreau, R L M; Queiroz, M L S; Palermo-Neto, J


    Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFκB expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-γ, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFκB signaling, being mediated by HPA axis activity and corticosterone.

  15. Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

    Rouine, J; Kelly, M E; Jennings-Murphy, C; Duffy, P; Gorman, I; Gormley, S; Kerskens, C M; Harkin, Andrew


    Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI. The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats. Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI. Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion. Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

  16. In vivo evidence against clomethiazole being neuroprotective against MDMA ('ecstasy')-induced degeneration of rat brain 5-HT nerve terminals by a free radical scavenging mechanism.

    Colado, M I; O'Shea, E; Esteban, B; Granados, R; Green, A R


    Clomethiazole is an effective neuroprotective agent against the degeneration of 5-HT neurones that follows administration of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). Since there is good evidence that free radical formation resulting from auto-oxidation of MDMA metabolites is responsible for the degeneration we have examined whether clomethiazole is a free radical scavenger. MDMA (15 mg/kg i.p.) increased the formation of 2,3- and 2,5-dihydroxybenzoic acids (2,3-DHBA and 2,5-DHBA) from salicylic acid perfused through a microdialysis tube implanted in the hippocampus, indicating increased free radical formation. Clomethiazole (50 mg/kg i.p.) administered 5 min prior and 55 min post MDMA prevented both the acute MDMA-induced hyperthermia and the rise in 2,3- and 2,5-DHBA. However, when the temperature of the MDMA + clomethiazole treated rats was kept elevated to that of the MDMA treated rats with a homeothermic blanket there was no inhibition of the MDMA-induced increase in 2,3-DHBA or 2,5-DHBA. These data suggest firstly that free radical formation is inhibited when the acute MDMA-induced hyperthermia is prevented. Secondly the data further indicate that clomethiazole has no free radical scavenging activity since the drug produces substantial neuroprotection when MDMA + clomethiazole treated rats are kept hyperthermic. This conclusion was strengthened by our observation that clomethiazole is a weak inhibitor (IC50 > 1 mM) of lipid peroxidation in synaptosomes when it had been induced by addition of FeCl2 + ascorbic acid.

  17. Effects on rat sexual behaviour of acute MDMA (ecstasy) alone or in combination with loud music.

    Cagiano, R; Bera, I; Sabatini, R; Flace, P; Vermesan, D; Vermesan, H; Dragulescu, S I; Bottalico, L; Santacroce, L


    The effects on sexual behaviour of acute low doses of methylendioxymethamphetamine (MDMA) (0.3, 1, 3 mg/kg/i.p.), alone or in combination with exposure to loud music (1 h stimulation), were investigated in Wistar rats. Results indicate that acute MDMA, at dose of 3 mg/kg, notably impaired copulatory behavior of sexually experienced male rats. In particular, MDMA-exposed animals exhibited a significant increase in intromission and ejaculation latencies as well as a significant decrease in percentage of rats displaying copulatory activity (one intromission at least). Surprisingly, one hour exposure to loud music, which per se resulted ineffective, antagonized the suppressive effect of MDMA by increasing the percent of animals displaying sexual activity. However, combined treatment of MDMA and music stimulation did not fully restore normal sexual behavior as the animals reaching ejaculation still showed a marked reduction of copulatory efficiency. These findings demonstrate that the systemic administration of a single low dose of MDMA, alone or in combination with loud music, which is commonly present in certain environments such as rave parties, notably impairs copulatory activity of male rats.

  18. Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.

    Thompson, Murray R; Callaghan, Paul D; Hunt, Glenn E; McGregor, Iain S


    The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

  19. A reconsideration and response to Parrott AC (2013) "Human psychobiology of MDMA or 'Ecstasy': an overview of 25 years of empirical research".

    Doblin, Rick; Greer, George; Holland, Julie; Jerome, Lisa; Mithoefer, Michael C; Sessa, Ben


    Parrott recently published a review of literature on MDMA/ecstasy. This commentary is a response to the content and tenor of his review, which mischaracterizes the literature through misstatement and omission of contrary findings, and fails to address the central controversies in the literature. The review makes several erroneous statements concerning MDMA-assisted psychotherapy, such as incorrect statements about research design and other statements that are baseless or contradicted by the literature. Though it critiques an attempt by other authors to characterize the risks of MDMA, the review fails to produce a competing model of risk assessment, and does not discuss potential benefits. Parrott does not represent an even-handed review of the literature, but instead recites dated misconceptions about neurotoxicity concerns involving the recreational drug ecstasy, which do not relate directly to the use of pure MDMA in a therapeutic setting. Unchallenged, Parrott's report may deter researchers from further investigating an innovative treatment that in early clinical trials has demonstrated lasting benefits for people with chronic, treatment-resistant post-traumatic stress disorder.

  20. Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") administration in awake rats

    Gramsbergen, Jan Bert; Cumming, Paul


    metabolism in freely moving rats using rapid sampling microdialysis (every minute) coupled to flow-injection analysis (FIA) with biosensors for glucose and lactate. Blood samples for analysis of glucose and lactate were taken at 30-45 min intervals before and after drug dosing and body temperature...... The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose...... depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1...

  1. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier integrity through a mechanism involving P2X7 receptors.

    Rubio-Araiz, Ana; Perez-Hernandez, Mercedes; Urrutia, Andrés; Porcu, Francesca; Borcel, Erika; Gutierrez-Lopez, Maria Dolores; O'Shea, Esther; Colado, Maria Isabel


    The recreational drug 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') produces a neuro-inflammatory response in rats characterized by an increase in microglial activation and IL-1β levels. The integrity of the blood-brain barrier (BBB) is important in preserving the homeostasis of the brain and has been shown to be affected by neuro-inflammatory processes. We aimed to study the effect of a single dose of MDMA on the activity of metalloproteinases (MMPs), expression of extracellular matrix proteins, BBB leakage and the role of the ionotropic purinergic receptor P2X7 (P2X7R) in the changes induced by the drug. Adult male Dark Agouti rats were treated with MDMA (10 mg/kg, i.p.) and killed at several time-points in order to evaluate MMP-9 and MMP-3 activity in the hippocampus and laminin and collagen-IV expression and IgG extravasation in the dentate gyrus. Microglial activation, P2X7R expression and localization were also determined in the dentate gyrus. Separate groups were treated with MDMA and the P2X7R antagonists Brilliant Blue G (BBG; 50 mg/kg, i.p.) or A-438079 (30 mg/kg, i.p.). MDMA increased MMP-3 and MMP-9 activity, reduced laminin and collagen-IV expression and increased IgG immunoreactivity. In addition, MDMA increased microglial activation and P2X7R immunoreactivity in these cells. BBG suppressed the increase in MMP-9 and MMP-3 activity, prevented basal lamina degradation and IgG extravasation into the brain parenchyma. A-438079 also prevented the MDMA-induced reduction in laminin and collagen-IV immunoreactivity. These results indicate that MDMA alters BBB permeability through an early P2X7R-mediated event, which in turn leads to enhancement of MMP-9 and MMP-3 activity and degradation of extracellular matrix.

  2. The impact of experimental design on assessing mechanism-based inactivation of CYP2D6 by MDMA (Ecstasy).

    Van, Linh M; Heydari, Amir; Yang, Jiansong; Hargreaves, Judith; Rowland-Yeo, Karen; Lennard, Martin S; Tucker, Geoffrey T; Rostami-Hodjegan, Amin


    MDMA (3-4-methylenedioxymethamphetamine, commonly known as Ecstasy) is a potent mechanism-based inhibitor (MBI) of cytochrome P450 2D6 (CYP2D6), causing quasi-irreversible inhibition of the enzyme in vitro. An evaluation of the in vivo implications of this phenomenon depends on the accuracy of the estimates of the parameters that define the inhibition in vitro, namely k(inact) (the maximal inhibition rate) and KI (the inactivation constant). These values are determined in two steps, pre-incubation of the enzyme with the inhibitor (enzyme inactivation), followed by dilution and further incubation to measure residual enzyme activity with a probe substrate. The aim of this study was to assess the impact of different dilutions and probe substrate concentrations on the estimates of k(inact) and KI using recombinantly expressed CYP2D6. Enzyme activity was measured by the conversion of dextromethorphan (DEX) to dextrorphan (DOR). Dilution factors of 1.25, 2, 5, 10, 25 and 50 (DEX at 30 microM) gave mean (+/-SE) values of k(inact) (min-1) of 0.20+/-0.06, 0.21+/-0.05, 0.31+/-0.06, 0.37+/-0.11, 0.51+/-0.10 and 0.58+/-0.08, respectively, and KI (microM) values (after correction for non-specific microsomal binding) of 2.22+/-1.90, 2.80+/-1.34, 5.78+/-2.07, 6.36+/-2.93, 3.99+/-1.57 and 4.86+/-1.37, respectively. Accordingly, high (e.g. 50 fold) and low (e.g. 1.25 fold) dilutions were associated with statistically significant differences in kinetic values (p <0.05). Varying DEX concentration (10-100 microM) was not associated with significant changes in k(inact) and KI values when a five-fold dilution was used (with the exception of a lower KI at 10 microM DEX). High dilution was also shown to reduce non-specific microsomal binding of MDMA. The changes in the two kinetic parameters were dependent on the experimental procedure and shown to be unlikely to have a material influence on the maximum inhibition of CYP2D6 expected in vivo after typical recreational doses of MDMA (50

  3. mCPP: an undesired addition to the ecstasy market.

    Bossong, M G; Brunt, T M; Van Dijk, J P; Rigter, S M; Hoek, J; Goldschmidt, H M J; Niesink, R J M


    A new ecstasy-like substance, meta-chlorophenylpiperazine (mCPP), has been detected in street drugs in the Netherlands. Theoretically, mCPP possesses the potential to become a non-neurotoxic alternative for methylenedioxymethamphetamine (MDMA), the regular psychoactive substance of ecstasy. Since its introduction on the Dutch market of synthetic drugs, the percentage of mCPP-containing tablets has increased, including both tablets that contain only mCPP and tablets containing a combination of mCPP and MDMA. These tablets occur in many different colours, shapes and sizes and with various logos, making it impossible to distinguish mCPP-containing tablets from regular MDMA tablets. In addition, the reports of users concerning the effects of mCPP are predominantly negative. All these aspects together lead to the conclusion that mCPP is an undesired addition to the ecstasy market from the user's perspective.

  4. Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy": the influence of gender and genetics (CYP2D6, COMT, 5-HTT.

    Ricardo Pardo-Lozano

    Full Text Available The synthetic psychostimulant MDMA (± 3,4-methylenedioxymethamphetamine, ecstasy acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6. It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT. This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6. A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles. Female subjects displayed more intense physiological (heart rate, and oral temperature and negative effects (dizziness, sedation, depression, and psychotic symptoms. Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/* determined greater cardiovascular effects, and with low functionality (met/* or s/s negative subjective effects (dizziness, anxiety, sedation. In conclusion, the contribution

  5. Instability of the ecstasy market and a new kid on the block: mephedrone.

    Brunt, Tibor M; Poortman, Anneke; Niesink, Raymond J M; van den Brink, Wim


    Recently, several reports have indicated instability of the ecstasy market in the Netherlands and other EU countries. In the current study, we demonstrate this instability in the Netherlands, showing a decrease of ecstasy tablets containing 3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in 2009. In addition, we describe a partial replacement of MDMA in tablets sold as ecstasy by a previously unseen substance, mephedrone (or 4-methylmethcathinone). Mephedrone was quantified and ecstasy tablets contained between 96 and 155 mg of this new compound. So far, no studies about mephedrone's effects have been published. For this study, we gathered information on the acute subjective effects of mephedrone from 70 regular ecstasy users. Overall, the majority of users considered the effects enjoyable. Mephedrone seemed to evoke effects similar to other amphetamine type psychostimulants, including MDMA. In contrast to MDMA, however, mephedrone induced strong feelings of craving in most users. If the unstable ecstasy market situation persists, the potential of mephedrone to substitute for MDMA might be substantial. Mephedrone, sold as ecstasy, is therefore likely to be a valid cause for health concern.

  6. Êxtase (MDMA: efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica Ecstasy (MDMA: pharmacological and toxic effects, mechanism of action and clinical management

    Caroline Addison Carvalho Xavier


    Full Text Available CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável.BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985

  7. The effects of ecstasy (MDMA on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals.

    Anne Klomp

    Full Text Available RATIONALE AND OBJECTIVE: Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure. METHODS: 5-HT transporter (SERT densities in the frontal cortex and midbrain were assessed with [(123I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14-18 years; developing brain, and late-exposed users (age-at-first exposure 18-36 years; mature brain. In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent rats and late-exposed (adult rats using the same radioligand. RESULTS: On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain exposed ecstasy users, whereas this was only 0.3% in late (mature brain exposed users (p=0.007. No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01 was observed as well, however only in the frontal cortex. CONCLUSIONS: These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.

  8. The solid-state terahertz spectrum of MDMA (Ecstasy) - A unique test for molecular modeling assignments

    Allis, Damian G.; Hakey, Patrick M.; Korter, Timothy M.


    The terahertz (THz, far-infrared) spectrum of 3,4-methylene-dioxymethamphetamine hydrochloride (Ecstasy) is simulated using solid-state density functional theory. While a previously reported isolated-molecule calculation is noteworthy for the precision of its solid-state THz reproduction, the solid-state calculation predicts that the isolated-molecule modes account for only half of the spectral features in the THz region, with the remaining structure arising from lattice vibrations that cannot be predicted without solid-state molecular modeling. The molecular origins of the internal mode contributions to the solid-state THz spectrum, as well as the proper consideration of the protonation state of the molecule, are also considered.

  9. The ecstasy and the agony; compression studies of 3,4-methylenedioxymethamphetamine (MDMA).

    Connor, Lauren E; Delori, Amit; Hutchison, Ian B; Nic Daeid, Niamh; Sutcliffe, Oliver B; Oswald, Iain D H


    MDMA (3,4-methylenedioxymethamphetamine) is a Class A substance that is usually found in a tableted form. It is only observed in one orthorhombic polymorph under ambient conditions. It shows slight positional disorder around the methlyenedioxy ring which persists during compression up to 6.66 GPa. The crystal quality deteriorates above 6.66 GPa where the hydrostatic limit of the pressure-transmitting medium is exceeded. The structure undergoes anisotropic compression with the a-axis compressing the greatest (12% cf. 4 and 10% for the b- and c-axes, respectively). This is due to the pattern of the hydrogen bonding which acts like a spring and allows the compression along this direction.

  10. The Correlation between the Communication of the Health Risks of Ecstasy (MDMA) and the Drug's Use among College Students.

    Campe, Brian; Frye, Kristin; Hood, Caitlin; Kuznekoff, Jeffrey; Parsons, Michael

    The purpose of this study is to explore the relationship between college students and their awareness of the hazardous effects of the drug Ecstasy. Ecstasy use has risen among college students even though readily available research shows Ecstasy use having extremely hazardous effects on its users. Research also shows a lack of communication about…

  11. Effects of alcohol (BAC 0.5‰) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety

    Veldstra, J.L.; Brookhuis, K.A.; De Waard, D.; Molmans, B.H.W.; Verstraete, A.G.; Skopp, G.; Janstos, R.


    Rational An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving

  12. Simultaneous analysis of six amphetamines and analogues in hair, blood and urine by LC-ESI-MS/MS. Application to the determination of MDMA after low ecstasy intake.

    Chèze, Marjorie; Deveaux, Marc; Martin, Claire; Lhermitte, Michel; Pépin, Gilbert


    A rapid and sensitive method using LC-MS/MS triple stage quadrupole for the determination of traces of amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), 3,4-methylenedioxyethamphetamine (MDEA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair, blood and urine has been developed and validated. Chromatography was carried out on an Uptisphere ODB C(18) 5 microm, 2.1 mm x 150 mm column (Interchim, France) with a gradient of acetonitrile and formate 2 mM pH 3.0 buffer. Urine and blood were extracted with Toxitube A (Varian, France). Segmented scalp hair was treated by incubation 15 min at 80 degrees C in NaOH 1M before liquid-liquid extraction with hexane/ethyl acetate (2/1, v/v). The limits of quantification (LOQ) in blood and urine were at 0.1 ng/mL for all analytes. In hair, LOQ was urine; in the range 5-500 pg/mg for MA, MDMA, MDEA and MBDB, and 20-500 pg/mg for AP and MDA. Inter-day precisions were urine at 1 and 50 ng/mL and urine was collected a few hours after (T+12h) and tested positive to amphetamines by immunoassay by a clinical laboratory. Blood and urine were sampled for forensic purposes at day 8 (D+8) and scalp hair at day 60 (D+60). No MDMA was detected in blood, but urine and hair were tested positive, respectively at 0.42 ng/mL and at 22 pg/mg in hair only in the segment corresponding to the period of the offence, while no MDA was detectable. This method allows the detection of MDMA up to 8 days in urine after single intake.

  13. Determinação de 3,4-metilenodioximetanfetamina (MDMA em comprimidos de Ecstasy por cromatografia líquida de alta eficiência com detecção por fluorescência (CLAE-DF Determination of 3,4-methylenedioxymethamphetamine (MDMA in Ecstasy tablets by high performance liquid chromatography with fluorescence detection (HPLC-FD

    José Luiz da Costa


    Full Text Available This paper describes the development and validation of simple and selective analytical method for determination of 3.4-methylenedioxymethamphetamine (MDMA in Ecstasy tablets, using high performance liquid chromatography with fluorescence detection. Analysis was performed in a reversed phase column (LiChrospher 100 C18, 150 x 4.6 mm, 5 µm, isocratic elution with phosphate buffer 25 mmol/L pH 3.0 and acetonitrile (95:5, v/v. The method presents adequate linearity, selectivity, precision and accuracy. MDMA concentration in analyzed tablets showed a remarkable variability (from 8.5 to 59.5 mg/tablet although the tablet weights were uniform, indicating poor manufacturing control thus imposing additional health risks to the users.

  14. Effects of long-term exposure of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") on neuronal transmitter transport, brain immuno-regulatory systems and progression of experimental periodontitis in rats.

    Breivik, Torbjørn; Bogen, Inger Lise; Haug, Kristin Huse; Fonnum, Frode; Opstad, Per-Kristian; Eide, Dag Marcus; Myhre, Oddvar


    The present study was designed to investigate the effects of long-term exposure (4 weeks) to the widely used narcotic drug and putative neurotoxicant 3,4-methylenedioxymetamphetamine (MDMA; "ecstasy") on neuronal transmitter transport and progression of experimental periodontitis in male Wistar rats. The rats were exposed to MDMA (10mg/kg/day i.p.) or saline five days a week for four consecutive weeks. Exposure to MDMA induced a significant reduction in the synaptosomal reuptake of serotonin, while the uptake of dopamine was significantly increased 24h after the last injection of MDMA. In contrast, the synaptosomal uptake of noradrenaline and the vesicular uptake through the vesicular monoamine transporter 2 were not affected. In the experiments of periodontitis development, ligature-induced periodontitis was induced three days prior to MDMA administration. Compared to controls, MDMA-treated rats developed significantly more periodontitis. In conclusion, our results show that long-term exposure to MDMA affects the serotonergic and dopaminergic transport systems in the rat brain and increased the susceptibility to the psychosomatic ailment periodontitis following disturbances of brain immune-regulatory systems. These results are interesting with respect to recent research showing that changes in neurotransmitter signalling may alter the reactivity of brain-controlled immunoregulatory systems controlling pathogenic microorganisms colonizing mucosal surfaces.

  15. Increased CRE-binding activity and tryptophan hydroxylase mRNA expression induced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rat frontal cortex but not in the hippocampus.

    García-Osta, Ana; Del Río, Joaquín; Frechilla, Diana


    A single administration of either 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") or p-chloroamphetamine (PCA) produced a rapid and marked reduction of serotonin (5-HT) content in rat frontal cortex and hippocampus. In the cortex of MDMA-treated rats, 5-HT levels returned to control values 48 h after drug administration. This recovery was correlated with an induction of CRE-binding activity and an enhanced expression of tryptophan hydroxylase (TPH) mRNA, the rate-limiting enzyme in 5-HT biosynthesis, suggesting that MDMA may up-regulate the TPH gene through a CREB-dependent mechanism. In the cortex of PCA-treated rats, neither a recovery of 5-HT levels nor changes in DNA-binding or TPH mRNA were found at the same time point. In the hippocampus of rats receiving either PCA or MDMA a decrease in TPH mRNA levels was found at all times, along with a reduced CRE-binding at the 8-h time point. The results show region-specific effects of MDMA. In the frontal cortex, the increased TPH expression suggests a compensatory response to MDMA-induced loss of serotonergic function.

  16. MDMA ( ecstasy ) abuse: neuropsychotoxicity and treatment%MDMA(迷魂药)的神经精神毒性及治疗




  17. HPLC Measurement of MDMA Content in Ecstasy Tablets Available in the Black Market of West Azerbaijan Province, Northwestern Iran

    Reza Ghafari


    Conclusion: There is variability in the physicochemical properties of ecstasy tablets available in the black market for illicit drugs in northwest Iran. This variability may potentially put abusers at increased risk of overdose due to inadvertent excess ingestion of the tablets to achieve desired effects and also experiencing more harm due to tablets adulterants.

  18. An In-Depth Qualitative Examination of the Ecstasy Experience: Results of a Focus Group with Ecstasy-Using College Students

    LEVY, KIRA B.; O'Grady, Kevin E.; Wish, Eric D.; Arria, Amelia M


    This study examined ecstasy use in 30 college students who participated in one of four 60-minute focus groups with other participants who also had a history of ecstasy use. Ten topics emerged in the sessions: 1) pill ingredients, 2) mechanism of MDMA effects, 3) reasons for initiating ecstasy use, 4) risky behaviors and ecstasy use, 5) sexual activity and ecstasy, 6) positive effects from ecstasy use, 7) negative effects related to ecstasy use, 8) ecstasy and polysubstance use, 9) perceived r...

  19. Accidental ingestion of Ecstasy in a toddler.

    Chang, Yi-Jung; Lai, Ming-Wei; Kong, Man-Shan; Chao, Hsun-Chin


    Toddlers who ingest the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') are at particularly high risk of serious neurological and cardiovascular side effects. We report of a 20-month-old male toddler who accidentally ingested Ecstasy. He presented with fever and seizures, tachycardia, hypertension, and hyperthermia. Urine amphetamine level was 2111 ng/mL. Treatment included rapid cooling, hydration, and support measures. Vital signs were regularly monitored. His condition became stable on day 2 and urine amphetamine level returned to normal on day 3 of hospitalization. His behavior, activity, and appetite had returned to their usual levels upon follow-up at our outpatient clinic. The incidence of drug abuse with MDMA has increased dramatically over the last decade in developed countries. It can be expected that accidental Ecstasy poisoning in children will increase as well. This case illustrates the need to consider the possibility of accidental Ecstasy ingestion in the differential diagnosis of a child suffering from convulsions with fever.

  20. Effects of alcohol (BAC 0.5‰) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety

    Veldstra, J.L.; Brookhuis, K.A.; de Waard, D.; Molmans, B.H.W.; Verstraete, A.G.; Skopp, G.; Janstos, R.


    Rational : An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are relatively rare. Objective : The present study was designed to establish the extent of driver impairment as a consequence of ecstasy or combined ecstasy and alcohol use as compared to dr...

  1. The influence of genetic and environmental factors among MDMA users in cognitive performance.

    Elisabet Cuyàs

    Full Text Available This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT, Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT, Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT. Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

  2. Effects of alcohol (BAC 0.5 parts per thousand) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety

    Veldstra, J.L.; Brookhuis, K.A.; De Waard, D.; Molmans, B.H.W.; Verstraete, A.G.; Skopp, G.; Jantos, R.

    An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are

  3. Crystal methamphetamine smoking among regular ecstasy users in Australia: increases in use and associations with harm.

    Kinner, Stuart A; Degenhardt, Louisa


    This study examined (a) changes in crystal methamphetamine use among regular ecstasy users (REU) in Australia and (b) associations of crystal use and smoking with demographics, drug use and harm. Cross-sectional surveys (2000-06) of REU in three Australian capital cities, and in 2006, 750 REU in all Australian capital cities. The interview included: demographics, drug use, risk behaviour, recent criminal activity and methamphetamine dependence using Severity of Dependence Scale. There was little change in overall methamphetamine use, but a marked increase in crystal methamphetamine smoking. Among recent methamphetamine users in 2006 (n = 606), crystal methamphetamine users (n = 364) reported more frequent methamphetamine use and higher levels of dependence. Compared with those who had used only other forms of methamphetamine, recent crystal methamphetamine users were more likely to 'binge' on drugs for > or = 48 hours, engage in crime and experience financial and legal problems related to drug use. Non-smoking crystal methamphetamine users (n = 78) more often reported recent injecting and heroin use. Recent smokers were more likely to have: greater polydrug use, recently overdosed on a 'party drug', and accessed medical services for their drug use. Many of these associations were accounted for by their injecting and heavier methamphetamine use, rather than smoking per se. Crystal methamphetamine smoking among REU has increased markedly and is associated with significant harm. This appears related to smokers' heavier levels of methamphetamine use. Effective harm reduction strategies should be tailored to these specific risks.

  4. Prior experience of morphine application alters the c-fos response to MDMA ('ecstasy') and cocaine in the rat striatum.

    Erdtmann-Vourliotis, M; Mayer, P; Riechert, U; Höllt, V


    Repeated morphine application usually leads to the development of tolerance but under certain circumstances sensitization may arise simultaneously. This phenomenon becomes obvious in behavioral tests as increasing locomotor activity and increasing drug self-administration during a course of chronic morphine application. It was suggested recently that sensitization could contribute to addiction. The molecular mechanisms of sensitization may include the long lasting increase in neuronal responsiveness to morphine which was observed in defined brain areas after repeated morphine injections. In this work, we studied whether morphine-sensitized Wistar rats also display an enhanced neuronal activity in response to other drugs of abuse (so called co-sensitization). The substances to be tested were injected as single doses 4 weeks after completion of a 10-day morphine pretreatment. MDMA (3, 4-methylenedioxymethamphetamine, 6 mg/kg) as a single test dose yielded a c-fos response in a wide range of brain areas. In the caudate putamen, the expression pattern of c-fos was clearly altered if the rats had received repeated morphine application previously. In this case, the MDMA-induced c-fos expression was markedly confined to the centromedial, mesolimbic aspect of the striatum whereas it had a diffuse appearance in rats not exposed to the opiate earlier. Cocaine application (50 mg/kg) elicited an intense c-fos expression in the medial striatum if the animals were morphine-pretreated; it was virtually absent in drug-naive rats after the same cocaine dose. Ten mg/kg cocaine had a similar but weaker effect. No difference in the c-fos expression pattern between morphine and saline pretreated animals was observed in the case of a THC (Delta(9)-tetrahydrocannabinol, 25 mg/kg) or an LSD (lysergic acid diethylamide, 1 mg/kg) test application. These findings imply that morphine sensitizes the brain towards other addicting drugs. In consequence, morphine sensitization obviously does not

  5. Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or 'ecstasy' and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices

    Kamboj, S K; Kilford, E. J.; Minchin, S; Moss, A.; Lawn, W.; Das, R. K.; Falconer, C. J.; Gilbert, P.; Curran, H.V.; Freeman, T. P.


    3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecs...

  6. Mechanisms underlying the hepatotoxic effects of ecstasy.

    Carvalho, Márcia; Pontes, Helena; Remião, Fernando; Bastos, Maria L; Carvalho, Félix


    3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a worldwide illegally used amphetamine-derived designer drug known to be hepatotoxic to humans. Jaundice, hepatomegaly, centrilobular necrosis, hepatitis and fibrosis represent some of the adverse effects caused by MDMA in the liver. Although there is irrefutable evidence of MDMA-induced hepatocellular damage, the mechanisms responsible for that toxicity remain to be thoroughly clarified. One well thought-of mechanism imply MDMA metabolism in the liver into reactive metabolites as responsible for the MDMA-elicited hepatotoxicity. However, other factors, including MDMA-induced hyperthermia, the increase in neurotransmitters efflux, the oxidation of biogenic amines, polydrug abuse pattern, and environmental features accompanying illicit MDMA use, may increase the risk for liver complications. Liver damage patterns of MDMA in animals and humans and current research on the mechanisms underlying the hepatotoxic effects of MDMA will be highlighted in this review.

  7. Untargeted metabolomics applied retrospectively to UPLC-HR-TOFMS data of whole blood samples from Danish drivers exposed to 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)

    Nielsen, Kirstine Lykke; Telving, Rasmus; Andreasen, Mette Findal;

    to evaluate the drug metabolism of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”). Despite of the untraditional experimental setup, and a very heterogeneous population with different concentrations of MDMA/kg blood weight, as well as unknown information about amount and time of administration in relation...... to blood sampling, it was possible to extract meaningful information. Various statistical methods were tested and their predictability was validated by the positive identification of MDMA blood metabolites. In addition, endogenous metabolites that may be related to energy metabolism, the serotonergic...

  8. 3,4-methylenedioxymethamphetamine (MDMA: current perspectives

    Meyer JS


    Full Text Available Jerrold S Meyer Department of Psychology, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA, USA Abstract: Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA. Most ecstasy users consume other substances as well, which complicates the interpretation of research in this field. The positively rated effects of MDMA consumption include euphoria, arousal, enhanced mood, increased sociability, and heightened perceptions; some common adverse reactions are nausea, headache, tachycardia, bruxism, and trismus. Lowering of mood is an aftereffect that is sometimes reported from 2 to 5 days after a session of ecstasy use. The acute effects of MDMA in ecstasy users have been attributed primarily to increased release and inhibited reuptake of serotonin (5-HT and norepinephrine, along with possible release of the neuropeptide oxytocin. Repeated or high-dose MDMA/ecstasy use has been associated with tolerance, depressive symptomatology, and persisting cognitive deficits, particularly in memory tests. Animal studies have demonstrated that high doses of MDMA can lead to long-term decreases in forebrain 5-HT concentrations, tryptophan hydroxylase activity, serotonin transporter (SERT expression, and visualization of axons immunoreactive for 5-HT or SERT. These neurotoxic effects may reflect either a drug-induced degeneration of serotonergic fibers or a long-lasting downregulation in 5-HT and SERT biosynthesis. Possible neurotoxicity in heavy ecstasy users has been revealed by neuroimaging studies showing reduced SERT binding and increased 5-HT2A receptor binding in several cortical and/or subcortical areas. MDMA overdose or use with certain other drugs can also cause severe morbidity and even death. Repeated use of MDMA may lead to dose escalation and the development of dependence, although such dependence is usually not as profound as is seen with many other drugs of abuse

  9. Ecstasy tablets intoxication with lethal autcome

    Đorđević Snežana


    Full Text Available Background. Ecstasy, 3,4-methylenedioxymethamphetamine (MDMA, is a synthetic compound increasingly popular as a recreational drug. Tablets known as ecstasy contain MDMA, but may also contain caffeine, ephedrine, paramethoxyamphetamine, 3,4-methylenedioxyamphetamine (MDA, amphetamine, methamphetamine, and ketamine. After absorption MDMA is metabolized to MDA, 4-hydroxy-3- metoxymetamphetamine (HMMA and 4-hydroxy-3- metoxyamphetamine (HMA. After that HMMA and HMA are conjugated and excreted by urine. The aim of this report was to confirm by toxicological post mortem analyses of poisoned person organs that ecstasy had been the cause of his death. Case report. We reported the death of a 17-year-old boy after the ingestion of ecstasy. MDMA and metabolites were determined by multicolumn high performance liquid chromatography with UV spectral detection (HPLC-UV. Toxicological tests showed the presence of MDMA in all samples. When examining post mortem material (the organs, the highest concentrations were measured in the stomach (835,97 μg/g and kidney (801,14 μg/g. The minimal concentration was in the liver (22,26 μg/g. Conclusion. The obtained results of MDMA and its metabolites concentrations showed abuse of a high dose of ecstasy. .

  10. Simultaneous liquid chromatographic-electrospray ionization mass spectrometric quantification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and its metabolites 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine and 3,4-methylenedioxyamphetamine in squirrel monkey and human plasma after acidic conjugate cleavage

    Mueller, Melanie; Peters, Frank T.; Huestis, Marilyn A.; Ricaurte, George A.; Maurer, Hans H.


    3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a psychoactive drug with abuse liability and neurotoxic potential. Specimen preparation of a recently presented LC–MS assay with electrospray ionization for quantifying MDMA and its main metabolites in squirrel monkey plasma was modified to include acidic hydrolysis to obtain total 3,4-dihydroxymethamphetamine and 4-hydroxy-3-methoxymethamphetamine. Method re-validation for squirrel monkey plasma and full validation for human plasma showed selectivity for all analytes. Recoveries were ≥71.0%. Changed specimen preparation or matrix did not affect accuracy or precision. No instability was observed after repeated freezing or in processed samples. Plasma MDMA and metabolites quantification, derived pharmacokinetic and toxicokinetic data and neurotoxicity research will benefit from this validated method. PMID:19131196

  11. In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin(2A) Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and Hallucinogen Users

    Erritzoe, David; Frokjaer, Vibe G.; Holst, Klaus K.


    .Objective: To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin(2A) receptor binding.Design: A positron emission tomography study of 24 young adult drug users and 21 nonusing control participants performed with carbon 11 (C-11)-labeled 3-amino-4-[2-[(di...

  12. Self-reported ecstasy (MDMA) use and past occurrence of sexually transmitted infections (STIs) in a cohort juvenile detainees in the USA.

    Stephens, Torrance; Holliday, Rhonda Conerly; Jarboe, Jerriyauna


    The current study was designed to determine the extent to which self-reported ecstasy use in a population of juvenile adolescent detainees in a southern state is associated with high-risk health behaviors pertaining to sexually transmitted infection (STI) symptomology and past history of STI occurrence. Participants were 2,260 juvenile offenders housed at selected Youth Development Campuses in the state of Georgia. Adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) are presented. Juveniles who reported having used ecstasy previously were more likely to report that they had sore bumps of blisters near their sex organs before (OR 1.28, 95 % CI 0.74-2.21), with males who had used ecstasy prior incarceration being more than two times more likely to indicated that they had experienced having a drip or drainage from the penis (OR 1.76, 95 % CI 0.72-4.32), having vaginal discharge or odor from their vagina (OR 2.33, 95 % CI 1.16-4.65).

  13. Comparison and evaluation of DRI methamphetamine, DRI ecstasy, Abuscreen ONLINE amphetamine, and a modified Abuscreen ONLINE amphetamine screening immunoassays for the detection of amphetamine (AMP), methamphetamine (MTH), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in human urine.

    Stout, Peter R; Klette, Kevin L; Wiegand, Russell


    The performances of four immunoassays (DRI amphetamines, DRI ecstasy, Abuscreen ONLINE amphetamines, and a modified Abuscreen ONLINE amphetamines) were evaluated for control failure rates, sensitivity, and specificity for amphetamine (AMP), methamphetamine (MTH), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA). The two DRI reagents and the ONLINE reagents were run according to manufacturer specifications using a Roche Hitachi Modular DDP system. The modified ONLINE reagent was calibrated with MDMA and had 16mM sodium periodate added to the R2 reagent. These assays were run on approximately 27,500 human urine samples and 7000 control urine samples prepared at 350 and 674 ng/mL over the course of 8 days. All assays were calibrated using a single point, qualitative cutoff standard with the manufacturer-recommended compound at the Department of Defense cutoff (500 ng/mL). Gas chromatography-mass spectrometry (GC-MS) confirmation was conducted on screened-positive samples. Control performance for the manufacturer recommended assays was excellent, with a maximum qualitative control failure rate of 2.03%. The modified ONLINE reagent demonstrated poor control performance with a maximum failure rate of 38.3% and showed no improved MDMA sensitivity when compared with the ONLINE reagent; the confirmation rate (20%) was improved when compared with the production ONLINE reagent (8%). The DRI ecstasy reagent provided improved sensitivity for MDMA as compared with the ONLINE reagent, with approximately 23% more samples screening and confirming positive for MDMA and a confirmation rate of approximately 90%. The DRI methamphetamine reagent had a low confirmation rate (6% or less) and produced numerous positives for samples with only ephedrine or pseudoephedrine present.

  14. Cannabis co-administration potentiates MDMA effects on temperature and heart rate

    Dumont, G.; Kramers, C.; Sweep, E.; Touw, D.; Van Hasselt, J.; De Kam, M.; Van Gerven, J.; Buitelaar, J.; Verkes, R.J.


    3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) is a frequently used club-drug in Western societies. Ecstasy users generally are multi-drug users, and cannabis (THC) is commonly combined with MDMA. MDMA is a potent psychostimulant, increasing heart rate, blood pressure and body temperature. TH

  15. The Effect of Ecstasy (MDMA on the Number of Ovary Follicles and Hormonal Axis of Pituitary-Gonadal in Immature Rats

    Zahra Allaeian


    Full Text Available Background & Objective: The widespread use of the pills of ecstasy has opened the floodgates to social damage. Severe kidney and liver damage as well amnesia and imbalance are some of ecstasy pills complications. This study evaluated the effect of these pills on the ovary and hormonal axis of pituitary-gonadal axis in rats.   Materials & Methods: Thirty-five female immature Wistar rats were divided into 5 groups of 7 rats, comprising control, sham, experimental 1, experimental 2, and experimental 3 groups. The control group did not receive any solvent or medication; the sham group received physiologic serum (0.2 cc once daily for 14 days; and the experimental groups of 1, 2, and 3 received a solution (0.2 cc once daily containing 0.5, 1, and 2 mg of medication for 14 days via intraperitoneal injection. Hormone measurement was done with the ELISA method. Ovaries were excised to prepare tissue sections and to investigate the number of ovarian follicles. The number of follicles was calculated via the physical dissector technique.   Results: There was a statistically significant difference in body and ovary weight between the control group and the experimental group 3. Also, the number of primary and Graafian follicles decreased significantly. The results did not show a statistically significant difference between the three experimental groups and the control group in terms of FSH and LH hormones, but the rate of progesterone hormone had a meaningful increase.   Conclusion: Use of ecstasy pills exerted a destructive impact on the ovary and progesterone hormone.

  16. A mechanistic insight into MDMA-mediated hepatotoxicity

    Antolino Lobo, I.


    methylenedioxymethamphetamine (MDMA, Ecstasy) is a popular drug of abuse among young people that can induce adverse effects. However, these effects lack a specific pattern, as consumption quantities are not correlated with the initiation and severity of the injury. MDMA can cause drug-induced liver

  17. A mechanistic insight into MDMA-mediated hepatotoxicity

    Antolino Lobo, I.|info:eu-repo/dai/nl/304833088


    methylenedioxymethamphetamine (MDMA, Ecstasy) is a popular drug of abuse among young people that can induce adverse effects. However, these effects lack a specific pattern, as consumption quantities are not correlated with the initiation and severity of the injury. MDMA can cause drug-induced liver

  18. Social contacts and Ecstasy offers: findings of a population-based study.

    Smirnov, Andrew; Najman, Jake M; Legosz, Margot; Wells, Helene; Kemp, Robert


    Ecstasy (MDMA) use is relatively common among young adults in many developed countries. However, little is known about how young non-users are first introduced to Ecstasy, including the relative contribution of peer networks and individual risk factors. We assess the role of social contact with Ecstasy-using peers in regard to young adults' exposure to offers of Ecstasy, using data from the Natural History Study, a population-based study conducted in Australia. Population screening of young adults (19- to 23-year-olds) identified a sample of young Ecstasy users (N = 315) and a comparison group of Ecstasy-naïve participants (N = 199). Two outcomes are considered: being exposed to any Ecstasy offers and being exposed to > 3 offers. Extensive social contact with Ecstasy users was defined as knowing > 10 Ecstasy users. Of the Ecstasy-naïve young adults, > 40% had ever received Ecstasy offers. Extensive social contact with Ecstasy users independently predicted exposure to multiple (> 3) Ecstasy offers for Ecstasy-naïve young adults. These findings indicate that Ecstasy offers are widespread among users and non-users of Ecstasy. For non-users, exposure to Ecstasy offers occurs through social contact with drug-using peers independently of individual risk factors. The pervasiveness of Ecstasy offers suggests that universal education concerning Ecstasy use is required.

  19. Profound Hypoglycemia with Ecstasy Intoxication

    Perliveh Carrera


    Full Text Available Background. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy is a synthetic drug that is commonly abused for its stimulant and euphoric effects. Adverse MDMA effects include hyperthermia, psychomotor agitation, hemodynamic compromise, renal failure, hyponatremia, and coma. However, endogenous hyperinsulinemia with severe persistent hypoglycemia has not been reported with MDMA use. Case Report. We report the case of a 29-year-old woman who remained severely hypoglycemic requiring continuous intravenous infusion of high-dose dextrose solutions for more than 24 hours after MDMA intoxication. Serum insulin and C-peptide levels confirmed marked endogenous hyperinsulinemia as the cause of the severe hypoglycemia. Why Should an Emergency Physician Be Aware of This? Immediate and frequent monitoring of blood glucose should be instituted in patients presenting with MDMA ingestion particularly if found to be initially hypoglycemic. Early recognition can help prevent the deleterious effects of untreated hypoglycemia that can add to the morbidity from MDMA use. Clinicians need to be aware of this side effect of MDMA so they can carefully monitor and treat it, especially in patients presenting with altered mental status.

  20. MDMA induces oxytocin release in humans

    Dumont, G.; Sweep, F.C.G.J.; Van Der Steen, R.V.; Hermsen, R.; Touw, D.J.; Buitelaar, J.K.; Verkes, R.J.


    Introduction: Appropriate social behavior is vital for human health and well-being, nevertheless the neurobiological mechanisms which mediate social behavior remain poorly understood. Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) is a street drug which gained widespread use in the 'club' scene,

  1. An in-depth qualitative examination of the ecstasy experience: results of a focus group with ecstasy-using college students.

    Levy, Kira B; O'Grady, Kevin E; Wish, Eric D; Arria, Amelia M


    This study examined ecstasy use in 30 college students who participated in one of four 60-minute focus groups with other participants who also had a history of ecstasy use. Ten topics emerged in the sessions: 1) pill ingredients, 2) mechanism of MDMA effects, 3) reasons for initiating ecstasy use, 4) risky behaviors and ecstasy use, 5) sexual activity and ecstasy, 6) positive effects from ecstasy use, 7) negative effects related to ecstasy use, 8) ecstasy and polysubstance use, 9) perceived risks of ecstasy use, and 10) motivational factors related to quitting ecstasy use. Most participants had a basic understanding of the contents of ecstasy pills, and the effects that ecstasy has on the brain and bodily functions. Participants reported positive effects on mood, social pressure, curiosity, availability, boredom, desire for an altered state of mind, desire to escape, self-medication, desire to have fun, and the ease of use of ecstasy in comparison to other drugs as reasons for initiating ecstasy use. They were divided regarding whether ecstasy increased the likelihood of engaging in risky behaviors, including risky sexual behavior. Participants described their experiences of both the positive and negative effects (physical and psychological) that they attributed to their use of ecstasy. All participants were polysubstance users, consuming a number of other substances simultaneously and concurrently with ecstasy. The majority was unaware of specific types of problems ecstasy could potentially cause and discounted its potential harm. Participants varied in their motivation for quitting ecstasy use, including negative personal experiences while using ecstasy, health concerns, and addiction/tolerance. Implications for prevention and intervention are discussed.

  2. Acute psychomotor effects of MDMA and ethanol (co-) administration over time in healthy volunteers

    Dumont, G J H; Schoemaker, R C; Touw, D J; Sweep, F C G J; Buitelaar, J K; van Gerven, J M A; Verkes, R J


    In Western societies, a considerable percentage of young people use 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol) in combination with ecstasy is common. The aim of the present study was to assess the acute psychomotor and subjective effects of (co-) administrati

  3. THC Prevents MDMA Neurotoxicity in Mice.

    Clara Touriño

    Full Text Available The majority of MDMA (ecstasy recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4 were pretreated with THC (3 mg/kg x 4 at room (21 degrees C and at warm (26 degrees C temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1 receptor antagonist AM251 and the CB(2 receptor antagonist AM630, as well as in CB(1, CB(2 and CB(1/CB(2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1 receptor antagonist AM251, neither in CB(1 and CB(1/CB(2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2 cannabinoid antagonist and in CB(2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1 receptor, although CB(2 receptors may also contribute to

  4. Toward an Ecstasy and Other Club Drug (EOCD) Prevention Intervention for Rave Attendees

    Yacoubian, George S., Jr.; Miller, Sarah; Pianim, Selwyn; Kunz, Michael; Orrick, Erin; Link, Tanja; Palacios, Wilson R.; Peters, Ronald J.


    A growing body of recent research has identified that "rave" attendees are at high risk for the use of "club drugs," such as 3,4-methylenedioxymeth-amphetamine (MDMA or "ecstasy"). Rave attendees, however, comprise only one of several club-going populations. In the current study, we explore the prevalence of ecstasy and other club drug (EOCD) use…

  5. Instability of the ecstasy market and a new kid on the block: mephedrone

    T.M. Brunt; A. Poortman; R.J.M. Niesink; W. van den Brink


    Recently, several reports have indicated instability of the ecstasy market in the Netherlands and other EU countries. In the current study, we demonstrate this instability in the Netherlands, showing a decrease of ecstasy tablets containing 3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in

  6. A mechanistic insight into 3,4-methylenedioxymethamphetamine ("ecstasy")-mediated hepatotoxicity

    Antolino-Lobo, I.; Meulenbelt, J.; van den Berg, M.; van Duursen, M.B.M.


    3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular drug of abuse among young people with stimulant and hallucinogenic properties. The drug is generally thought to be safe among consumers due to its low-mortality rates. However, MDMA-adverse effects can occur and the risks are not clear

  7. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.

    Dumont, G J H; Sweep, F C G J; van der Steen, R; Hermsen, R; Donders, A R T; Touw, D J; van Gerven, J M A; Buitelaar, J K; Verkes, R J


    MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

  8. MDMA--摇头丸

    赵成正; 刘彦红; 郑继旺


    @@ MDMA是亚甲二氧基甲基苯丙胺的英文缩写(3,4-methylenedioxymethamphetamine,MDMA),俗称"Ecstasy"(迷魂药),"XTC"或"E",是苯丙胺类中枢兴奋剂中具致幻作用中的一种.由于服用MDMA能使人产生"亲密"感和幻觉,人们也称其为"亲密药"(hug drug).在我国,因滥用者滥用后可即兴随音乐剧烈地摆动头部而不觉痛苦,得名"摇头丸".

  9. The significance of ecstasy use to dental practice.

    Maloney, William James; Raymond, George


    3,4 Methylenedioxymethampetamine (MDMA), commonly known as ecstasy, is an illicit drug used by individuals seeking mood enhancement. Ecstasy's pharmacology, systemic, oral and dental manifestations are presented. Use of this drug is not limited to a particular socioeconomic class and, as such, all practicing dentists must be aware of both the intra-oral effects of this drug and any possible alterations to dental treatment that might become necessary. Dental manifestations include bruxism, increased incidence of caries, xerostomia and oral ulcers.

  10. Careers in ecstasy use: do ecstasy users cease of their own accord? Implications for intervention development

    Schaalma Herman P


    Full Text Available Abstract Background Ecstasy (MDMA, 3, 4-methylenodioxymethamphetamine use is widespread in the Netherlands, with a lifetime prevalence of 4.3%, and two-thirds of dance party visitors being ecstasy users. However, research into Dutch ecstasy use patterns is lacking. In addition, recent studies suggest that ecstasy users cease their use automatically, which implies that interventions would do better to better focus on the promotion of harm reduction strategies than on inducing cessation. The current study addresses this process of ecstasy cessation. Methods 32 participants from the Dutch dance scene were interviewed, and the results were systematically analysed using NVivo. Results Most ecstasy users had started to use out of curiosity. During use, users applied a host of harm reduction strategies, albeit inconsistently and sometimes incorrectly. Most users appeared to cease ecstasy use automatically because of loss of interest or changing life circumstances (e.g. a new job or relationship. Conclusion It appears that cessation of ecstasy use is largely determined by environmental variables and not by health concerns. This supports the idea that health promotion resources are better spent in trying to promote consistent and correct application of harm reduction practices than in trying to induce cessation.

  11. Dysfunctional overnight memory consolidation in ecstasy users.

    Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell


    Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users.

  12. Fear, Rationality and Opportunity: Reasons and Motives for Not Trying Ecstasy

    Vervaeke, Hylke Karen Eva; Benschop, Annemieke; Korf, Dirk Jan


    Aim: To gain more insight into the reasons and motives why people do not start taking ecstasy. Method: As part of the NeXT Study, we prospectively monitored 188 subjects who were ecstasy-naive at baseline but seemed likely to take ecstasy (MDMA) of their own accord during the course of the study. After an 11- to 26-month follow-up period, 160…

  13. Treadmill exercise alters ecstasy- induced long- term potentiation disruption in the hippocampus of male rats.

    Sajadi, Azam; Amiri, Iraj; Gharebaghi, Alireza; Komaki, Alireza; Asadbeigi, Masoumeh; Shahidi, Siamak; Mehdizadeh, Mehdi; Soleimani Asl, Sara


    3, 4-methylenedioxymethamphetamine (MDMA) or ecstasy is a derivative of amphetamine that leads to long term potentiation (LTP) disruption in the hippocampal dentate gyrus (DG). Exercise has been accepted as a treatment for the improvement of neurodegenerative disease. Herein, the effects of exercise on the MDMA- induced neurotoxicity were assessed. Male Wistar rats received intraperitoneal injection of MDMA (10 mg/kg) and exercised for one month on a treadmill (Simultaneously or asynchronously with MDMA). LTP and expression of BDNF were assessed using electrophysiology and western blotting methods, respectively. MDMA attenuated the field excitatory post-synaptic potential (fEPSP) slope in comparison with the control group, whereas treadmill exercise increased this parameter when compared to MDMA group. Furthermore, BDNF expression significantly decreased in MDMA group and treadmill exercise could increase that. In conclusion, results of this study suggest that synchronous exercise is able to improve MDMA-induced LTP changes through increase of BDNF expression in the hippocampus of rats.

  14. The Preservation of in vivo Phosphorylated and Activated Uncoupling Protein 3 (UCP3) in Isolated Skeletal Muscle Mitochondria following Administration of 3,4-Methylenedioxymethamphetamine (MDMA aka Ecstasy) to Rats/Mice


    PUBLISHED Previous researchers have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) induced hyperthermia, in skeletal muscle of animals, is uncoupling protein 3 (UCP3) dependent. In light of our investigations that in vivo phosphorylation of UCP1 is augmented under conditions of cold-acclimation, we set out to investigate whether (a) UCP3 was phosphorylated in vivo and (b) whether in vivo phosphorylation of UCP3 resulted in increased proton leak following MDMA administration to ...

  15. Cannabinoids, opioids and MDMA: neuropsychological interactions related to addiction.

    Robledo, Patricia


    3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative with psychostimulant properties. This substance is widely used around the world by young adults in recreational settings. One of the most remarkable characteristic of ecstasy users is the concurrent consumption of several other drugs of abuse including psychostimulants, alcohol, tobacco, LSD, cannabis and opioids. This poly-drug pattern of use is now prompting research towards understanding how the combination of MDMA with cannabis and opioids could affect neuropsychobiological processes related to addiction. As with other drugs of abuse, behavioural evidence has been presented supporting the role of the endocannabinoid system as a modulator of the rewarding/reinforcing properties of MDMA. On the other hand, the neurochemical substrate for the complex interactions between the endocannabinoid system and MDMA is poorly understood. MDMA also modulates the activity of the dynorphinergic and enkephalinergic systems in several brain structures related to addiction, as it has been shown for other psychostimulants. The work regarding the contribution of micro- and delta-opioid receptors in the rewarding effects of MDMA shows differential results in pharmacological studies in rats, with respect to studies using knock-out mice. The present review describes the behavioural and neurochemical interactions between MDMA, cannabinoids and opioids with respect to addiction processes.

  16. The varieties of ecstasy experience: a phenomenological ethnography.

    Leneghan, Sean


    Ecstasy (MDMA) has attracted widespread attention with its association as a "recreational substance" that is concentrated in club and rave settings. This paper outlines a phenomenologically grounded ethnographic study of the experiences of ecstasy users in the Sydney, Australia, area. I espouse phenomenology as a framework for describing and understanding these experiences. A number of excerpts are presented from my primary corpus of ethnographic material. For the purposes of this paper I assemble user's reports into nine thematic areas: (1) initial reactions and peaking; (2) the rush; (3) plateau; (4) coming down/scattering; (5) love; (6) peace, love, understanding, and respect; (7) connections on ecstasy; (8) unificatory experiences; (9) returning to baseline. The typical experiences presented in these reports confirm and extend interdisciplinary approaches to understanding ecstasy. I suggest that a context-specific approach that is phenomenologically attuned to user's experiences with ecstasy can contribute to the growing body of literature undertaken in the Australian and international research community.

  17. MDMA as a Probe and Treatment for Social Behaviors.

    Heifets, Boris D; Malenka, Robert C


    MDMA, better known as the recreational drug "ecstasy," is well known for stimulating a feeling of closeness and empathy in its users. We advocate that exploring its mechanism of action could lead to new treatments for psychiatric conditions characterized by impairments in social behavior.

  18. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology.

    Sáez-Briones, P; Hernández, A


    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, "Ecstasy") is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an "open mind state", may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues.

  19. Acute psychomotor, memory and subjective effects of MDMA and THC co-administration over time in healthy volunteers

    Dumont, G.J.H.; Van Hasselt, J.G.C.; De Kam, M.; Van Gerven, J.M.A.; Touw, D.J.; Buitelaar, J.K.; Verkes, R.J.


    In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') and cannabis. The aim of the present study was to assess the acute effects of co-administration of MDMA and THC (the main psychoactive compound

  20. The variability of ecstasy tablets composition in Brazil.

    Togni, Loraine R; Lanaro, Rafael; Resende, Rodrigo R; Costa, Jose L


    The content of ecstasy tablets has been changing over the years, and nowadays 3,4-methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The aim of this study was to investigate the chemical composition in the seized tablets labeled as ecstasy. We analyzed samples from 150 different seizures made by Sao Paulo's State Police by gas chromatography-mass spectrometry. MDMA was present in 44.7% of the analyzed samples, and another twenty different active substances were identified in these tablets, such as caffeine, 2C-B, piperazines, amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of these samples. The results demonstrate a huge shift in the pattern of trafficking of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit psychoactive substances, in a clear attempt to bypass the law. The great variability in the tablets composition may lead to an increased risk of drug poisoning.

  1. [Acute and long-term effects of ecstasy].

    Salzmann, Julie; Marie-Claire, Cynthia; Noble, Florence


    Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term Moreover, MDMA has been shown to induce long-term deleterious effects and provoke neurotoxic affecting the serotoninergic system. However, the psychopathological consequences of such neurotoxicity are still controversial, particularly since many ecstasy consumers are multi-drug users. A complex pharmacological profile The mechanism of action of MDMA involves various neurobiological systems (serotonin, dopamine, noradrenalin), that may all interact.

  2. Characteristics of pregnant women who use ecstasy (3, 4-methylenedioxymethamphetamine).

    Ho, E; Karimi-Tabesh, L; Koren, G


    To determine the characteristics of pregnant women who use Ecstasy (3,4-methylenedioxymethamphetamine, MDMA), and to identify reproductive risk factors associated with this group of women. Prospective, observational study. Pregnant women who have contacted the Motherisk Alcohol and Substance Use Helpline at The Hospital for Sick Children, in Toronto, about exposure to drugs, chemicals, infection or radiation. All inquiries from December 1998 to October 2000 concerning pregnant women who reported use of MDMA, and control cases of women not exposed to MDMA selected within the same week of the MDMA callers. Age, maternal demographics, pregnancy characteristics, patterns of alcohol, tobacco, and illicit drug use, psychological/emotional status, sexually transmitted disease, MDMA method and pattern of use, and adverse drug reactions after ingestion of MDMA. The 132 pregnant women who used MDMA were significantly younger (mean 23.2 vs. 31.2 years, Palcohol (66.4% vs. 37.3%, Ppsilocybin were used more frequently among the MDMA sample. Over a third of MDMA users reported psychiatric/emotional problems, including 6.5% with a clinically diagnosed condition that was being treated with medication and/or counseling. Pregnant women who use MDMA tend to be young, single, and report psychological morbidity, and have a clustering of risk factors that may compromise the pregnancy and fetus. Smoking, heavy alcohol intake, and polydrug use, combined with a higher than expected rate of unplanned pregnancies, increases the risk of fetal exposure to potentially harmful substances. It is important to account for the range of confounding risk factors among women who use MDMA in order to define possible direct effects of MDMA in pregnancy.

  3. Methaemoglobinemia Induced by MDMA?

    L. L. W. Verhaert


    Full Text Available Case. A 45-year-old man with a blank medical history presented at the emergency room with dizziness and cyanosis. Physical examination showed cyanosis with a peripheral saturation (SpO2 of 85%, he did not respond to supplemental oxygen. Arterial blood gas analysis showed a striking chocolate brown colour. Based on these data, we determined the arterial methaemoglobin concentration. This was 32%. We gave 100% oxygen and observed the patient in a medium care unit. The next day, patient could be discharged in good condition. Further inquiry about exhibitions and extensive history revealed that the patient used MDMA (3,4- methylenedioxymethamphetamine, the active ingredient of ecstasy. Conclusion. Acquired methaemoglobinemia is a condition that occurs infrequently, but is potentially life threatening. Different nutrients, medications, and chemicals can induce methaemoglobinemia by oxidation of haemoglobin. The clinical presentation of a patient with methaemoglobinemia is due to the impossibility of O2 binding and transport, resulting in tissue hypoxia. Important is to think about methaemoglobin in a patient who presents with cyanosis, a peripheral saturation of 85% that fails to respond properly to the administration of O2. Because methaemoglobin can be reduced physiologically, it is usually sufficient to remove the causative agent, to give O2, and to observe the patient.

  4. Methaemoglobinemia Induced by MDMA?

    Verhaert, L L W


    Case. A 45-year-old man with a blank medical history presented at the emergency room with dizziness and cyanosis. Physical examination showed cyanosis with a peripheral saturation (SpO(2)) of 85%, he did not respond to supplemental oxygen. Arterial blood gas analysis showed a striking chocolate brown colour. Based on these data, we determined the arterial methaemoglobin concentration. This was 32%. We gave 100% oxygen and observed the patient in a medium care unit. The next day, patient could be discharged in good condition. Further inquiry about exhibitions and extensive history revealed that the patient used MDMA (3,4- methylenedioxymethamphetamine, the active ingredient of ecstasy). Conclusion. Acquired methaemoglobinemia is a condition that occurs infrequently, but is potentially life threatening. Different nutrients, medications, and chemicals can induce methaemoglobinemia by oxidation of haemoglobin. The clinical presentation of a patient with methaemoglobinemia is due to the impossibility of O(2) binding and transport, resulting in tissue hypoxia. Important is to think about methaemoglobin in a patient who presents with cyanosis, a peripheral saturation of 85% that fails to respond properly to the administration of O(2). Because methaemoglobin can be reduced physiologically, it is usually sufficient to remove the causative agent, to give O(2), and to observe the patient.

  5. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans.

    Kirkpatrick, Matthew G; Francis, Sunday M; Lee, Royce; de Wit, Harriet; Jacob, Suma


    MDMA (±3,4-methylenedioxymethamphetamine, 'ecstasy') is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its pro-social effects by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5mg/kg), intranasal oxytocin (20IU or 40IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7pg/ml at approximately 90-120min, compared to 18.6pg/ml after placebo. Intranasal oxytocin (40IU, but not 20IU) increased plasma oxytocin levels to 48.0pg/ml, 30-60min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., 'High' and 'Like Drug'), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects.

  6. Drug interaction between ethanol and 3,4-methylenedioxymethamphetamine ("ecstasy").

    Upreti, Vijay V; Eddington, Natalie D; Moon, Kwan-Hoon; Song, Byoung-Joon; Lee, Insong J


    Alcohol (ethanol) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are frequently co-abused, but recent findings indicate a harmful drug interaction between these two agents. In our previous study, we showed that MDMA exposure inhibits the activity of the acetaldehyde (ACH) metabolizing enzyme, aldehyde dehydrogenase2 (ALDH2). Based on this finding, we hypothesized that the co-administration of MDMA and ethanol would reduce the metabolism of ACH and result in increased accumulation of ACH. Rats were treated with MDMA or vehicle and then administered a single dose of ethanol. Liver ALDH2 activity decreased by 35% in the MDMA-treated rats compared to control rats. The peak concentration and the area under the concentration versus time curve of plasma ACH were 31% and 59% higher, respectively, in the MDMA-ethanol group compared to the ethanol-only group. In addition, the MDMA-ethanol group had 80% higher plasma transaminase levels than the ethanol-only group, indicating greater hepatocellular damage. Our results not only support a drug interaction between MDMA and ethanol but a novel underlying mechanism for the interaction.

  7. Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats

    Costanzo Francesco S


    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. Results We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Conclusion Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties.

  8. Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits.

    Pedersen, N P; Blessing, W W


    3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") increases body temperature. This process could be associated with increased cutaneous blood flow, as normally occurs with exercise-induced hyperthermia. Alternatively, an MDMA-induced fall in cutaneous blood flow could contribute to the hyperthermia by diminishing normal heat transfer from the body to the environment. We investigated these possibilities by administering MDMA (1.5-6 mg/kg, i.v.) to conscious freely moving rabbits, determining effects on body temperature, cutaneous blood flow (measured by a Doppler ultrasonic probe that was chronically implanted around the ear pinna artery), and other cardiovascular parameters. MDMA caused a dose-dependent increase in body temperature (from 38.3 +/- 0.3 to 41.2 +/- 0.4 degrees C after 6 mg/kg; p mechanism whereby MDMA causes hyperthermia. Reversal of cutaneous vasoconstriction by appropriate pharmacological means could be of therapeutic benefit in humans suffering from life-threatening hyperthermia induced by MDMA.

  9. Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

    Lansbergen, M.M.; Dumont, G.J.H.; Gerven, J.M. van; Buitelaar, J.K.; Verkes, R.J.


    RATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol

  10. Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

    Lansbergen, M.M.; Dumont, G.J.H.; Gerven, J.M. van; Buitelaar, J.K.; Verkes, R.J.


    RATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol o

  11. Differential effects of MDMA and methylphenidate on social cognition.

    Schmid, Yasmin; Hysek, Cédric M; Simmler, Linda D; Crockett, Molly J; Quednow, Boris B; Liechti, Matthias E


    Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective 'empathogenic' effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug.

  12. Dantrolene for the treatment of MDMA toxicity.

    Grunau, Brian E; Wiens, Matthew O; Greidanus, Marc


    MDMA (3,4-methylenedioxymethamphetamine), popularly known as “Ecstasy,” was first introduced and patented by Merck & Co., Inc., in 1914 as an appetite suppressant. Currently, its primary role is as an illegal stimulant used to produce a euphoric effect during parties. This case report de scribes a 31-year-old man who, after taking 3 tablets of Ecstasy, presented to an emergency department with a decreased level of consciousness and became progressively hyperthermic and rigid. During the course of his acute illness, his temperature reached 42.2°C rectally. He was given mechanical ventilation. He was aggressively cooled and dantrolene was initiated. Soon after the administration of dantrolene his temperature decreased and his rigidity began to resolve. The only complication was rhabdomyolysis with a creatine kinase level increasing to over 150 μkat/L. This did not progress to acute renal failure. The patient made a full recovery and was discharged to psychiatry for assessment.

  13. Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes.

    Shenouda, Sylvia K; Varner, Kurt J; Carvalho, Felix; Lucchesi, Pamela A


    Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown, oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included alpha-methyl dopamine, N-methyl alpha-methyl dopamine and 2,5-bis(glutathion-S-yl)-alpha-MeDA. Dihydroethidium was used to detect drug-induced increases in reactive oxygen species (ROS) production in ventricular myocytes. Contractile function and changes in intracellular calcium transients were measured in paced (1 Hz), Fura-2 AM loaded, myocytes using the IonOptix system. Production of ROS in ventricular myocytes treated with MDMA was not different from control. In contrast, all three metabolites of MDMA exhibited time- and concentration-dependent increases in ROS that were prevented by N-acetyl-cysteine (NAC). The metabolites of MDMA, but not MDMA alone, significantly decreased contractility and impaired relaxation in myocytes stimulated at 1 Hz. These effects were prevented by NAC. Together, these data suggest that MDMA-induced oxidative stress in the left ventricle can be due, at least in part, to the metabolism of MDMA to redox active metabolites.

  14. Benzylpiperizine-based party pills' impact on the Auckland City Hospital Emergency Department Overdose Database (2002-2004) compared with ecstasy (MDMA or methylene dioxymethamphetamine), gamma hydroxybutyrate (GHB), amphetamines, cocaine, and alcohol.

    Theron, Lynn; Jansen, Karl; Miles, Jennifer


    To examine the impact of 'party pills' (PP; herbal highs) on the Auckland City Hospital Emergency Department Overdose Database 2002-2004, and to present figures for five other substances in that database. Auckland City Hospital's Emergency Department's overdose database was reviewed for 2002, 2003, and 2004 for 'herbal ingestions' and 'party pills' (PP), ecstasy, methamphetamine, GHB, cocaine, and alcohol. Adverse effects attributed to PP were examined. In 2002, 1 patient presented with PP ingestion; 4 presented in 2003 and 21 in 2004 respectively (poverdose database for 2004. 'Party pills' appeared to have a minor impact on the overdose database at Auckland City Hospital between 2002 and 2004. There was a significant decrease in GHB presentations from 2003 to 2004 (poverdose presentations.

  15. Is emotional intelligence impaired in ecstasy-polydrug users?

    Craig, L; Fisk, J E; Montgomery, C; Murphy, P N; Wareing, M


    Previous findings report use of the drug ecstasy (MDMA) to be associated with lower emotional intelligence (EI), and compromised functioning in brain areas responsible for emotion. This study explored the relationship between ecstasy use, EI, mood and parenting styles. Questionnaire measures of drug use, lifestyle, parenting style and EI were obtained, with separate IQ measures for fluid intelligence (Ravens matrices) and pre-morbid intelligence [National Adult Reading Test (NART)]. Current mood measures were obtained from an adjective checklist. The sample comprised 78 ecstasy/polydrug users, 38 cannabis only users and 34 non-drug users. Drug use was categorised at three levels (non-user, cannabis-only user and ecstasy-polydrug user). Factorial ANOVA using drug use as an independent variable showed no significant group effects in EI. EI showed significant correlations with current mood that were positive for arousal and negative for both anxiety and depression. EI was also significantly and positively correlated with the perceived degree of parental control. Regression analyses showed that these relationships remained significant after controlling for differences in IQ, age, gender, and ecstasy use. Adverse mood effects specifically associated with ecstasy use were significantly related to lower EI, and were independent of IQ, age and gender. Higher EI was significantly associated with ecstasy-related precautions used when taking this drug. Contrary to earlier findings, ecstasy-polydrug users did not differ from non-users on EI. However, self-reported ecstasy-related mood disturbances were related to lower EI, with the compromising of orbitofrontal cortical functioning being possible here.

  16. [Acute and long-term effects of ecstasy

    Salzmann, Julie; Marie-Claire, Cynthia; Noble, Florence


    International audience; Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term More...

  17. Síndrome de Cotard associada ao uso de ecstasy Cotard’s syndrome induced by ecstasy

    Rodrigo Nicolato


    Full Text Available O termo ecstasy é usado para descrever diversas substâncias que compartilham estruturas químicas e efeitos semelhantes, referindo-se mais comumente a 3,4-metilenodioximetanfetamina (3,4-MDMA. Os efeitos psíquicos da MDMA são, sobretudo, alucinógenos e estimulantes. A tendência atual considera o delírio de Cotard como sendo a crença delirante de estar morto ou de que seus órgãos estejam paralisados ou podres, independentemente do diagnóstico do paciente. Neste artigo, relatamos o caso clínico de um paciente que apresentou quadro psicótico com delírios hipocondríacos e alucinações olfativas com características de síndrome de Cotard associado ao uso crônico de ecstasy. Foi medicado com olanzapina e obteve remissão completa dos sintomas.The term ecstasy is used to describe various substances that share similar chemical structures and effects, often referring to 3,4-methylenedioxy-N-methylamphetamine (3,4-MDMA. MDMA psychic effects are mainly hallucinatory and stimulatory. Current trends consider Cotard’s delusion as a delusional belief of being dead or having paralyzed or rotten organs, independent of the diagnosis the patient has received. This case report is about a psychotic episode where the patient presented with hypochondriac delusion and olfactory hallucinations resembling Cotard’s syndrome and associated with ecstasy abuse. He was given olanzapine and achieved total remission from symptoms.

  18. Posterior spinal artery aneurysm rupture after 'Ecstasy' abuse.

    Johnson, Jeremiah; Patel, Shnehal; Saraf-Lavi, Efrat; Aziz-Sultan, Mohammad Ali; Yavagal, Dileep R


    Posterior spinal artery (PSA) aneurysms are a rare cause of subarachnoid hemorrhage (SAH). The commonly abused street drug 3,4-methylenedioxymethamphetamine (MDMA) or 'Ecstasy' has been linked to both systemic and neurological complications. A teenager presented with neck stiffness, headaches and nausea after ingesting 'Ecstasy'. A brain CT was negative for SAH but a CT angiogram suggested cerebral vasculitis. A lumbar puncture showed SAH but a cerebral angiogram was negative. After a spinal MR angiogram identified abnormalities on the dorsal surface of the cervical spinal cord, a spinal angiogram demonstrated a left PSA 2 mm fusiform aneurysm. The patient underwent surgery and the aneurysmal portion of the PSA was excised without postoperative neurological sequelae. 'Ecstasy' can lead to neurovascular inflammation, intracranial hemorrhage, SAH and potentially even de novo aneurysm formation and subsequent rupture. PSA aneurysms may be treated by endovascular proximal vessel occlusion or open surgical excision.

  19. Tracking Ecstasy Trends in the United States with Data from Three National Drug Surveillance Systems

    Yacoubian, George S., Jr.


    Anecdotal reports have suggested that the use of 3,4-methylenedioxymeth-amphetamine (MDMA or "ecstasy") is a prodigious problem across the United States. Unfortunately, no longitudinal evidence exists to support this contention. In the current study, data from the Drug Abuse Warning Network (DAWN), Monitoring the Future (MTF), and National…

  20. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration

    Dumont, G J H; Sweep, F C G J; van der Steen, R; Hermsen, R; Donders, A R T; Touw, D J; van Gerven, J M A; Buitelaar, J K; Verkes, R J


    MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in anima

  1. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.

    Dumont, G.J.H.; Sweep, C.G.J.; Steen, R. van der; Hermsen, R.; Donders, A.R.T.; Touw, D.J.; Gerven, J.M. van; Buitelaar, J.K.; Verkes, R.J.


    MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in anima

  2. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population.

    Wolff, Kim; Tsapakis, E M; Winstock, A R; Hartley, D; Holt, D; Forsling, M L; Aitchison, Katherine J


    Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p ecstasy-using "clubbers", which has important clinical implications.

  3. 近红外光谱技术应用于摇头丸中MDMA、MA无损定量分析的研究%Nondestructive Determination of MDMA and MA in Ecstasy by Near Infrared Spectroscopy

    吴国萍; 相秉仁


    提出了用近红外漫反射光潜快速无损测定摇头丸中亚甲二氧基甲基苯丙胺(MDMA)、甲基苯丙胺(MA)含量的新方法.收集含MDMA摇头丸56份和含MA摇头丸58份,采用GC-MS确定其中MDMA和MA质量分数分别为0.64%~53.83%,0.37%~5.81%.在12 000~4 000 cm-1扫描样品,以交叉验证误差均方根(RMSECV)为指标,通过筛选,对各组分确定了用于建模的最优近红外波段和光谱预处理方法,采用偏最小二乘算法建立了近红外光谱与这2组分GC-MS分析值之间的校正模型,并以此分别预测21个样本.δ代表预测样本NIR值/GC-MS值,MDMA和MA在裸片和塑料包装中δ值的均值为99%、101%、100%、101%,RSD分别为7.33%、20.3%、4.52%、12.3%.该方法可对摇头丸裸片中MDMA和MA进行快速无损分析,结果可靠,为刑事案件中毒品成分的测定提供了一种新的分析手段.

  4. Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA.

    Hasler, F; Studerus, E; Lindner, K; Ludewig, S; Vollenweider, F X


    Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2A receptors also contributes to the overall action of MDMA. The role of 5-HT1A receptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences of manipulation at the 5-HT1A receptor system on cognitive and subjective effects of MDMA, a receptor blocking study using the mixed beta-adrenoreceptor blocker/5-HT1A antagonist pindolol was performed. Using a double-blind, placebo-controlled within-subject design, 15 healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN), MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA). Tasks from the Cambridge Neuropsychological Test Automated Battery were used for the assessment of cognitive performance. Psychometric questionnaires were applied to measure effects of treatment on core dimensions of Altered States of Consciousness, mood and state anxiety. Compared with PL, MDMA significantly impaired sustained attention and visual-spatial memory, but did not affect executive functions. Pre-treatment with PIN did not significantly alter MDMA-induced impairment of cognitive performance and only exerted a minor modulating effect on two psychometric scales affected by MDMA treatment ('positive derealization' and 'dreaminess'). Our findings suggest that MDMA differentially affects higher cognitive functions, but does not support the hypothesis from animal studies, that some of the MDMA effects are causally mediated through action at the 5-HT1A receptor system.

  5. Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test.

    Ando, Romeo D; Benko, Anita; Ferrington, Linda; Kirilly, Eszter; Kelly, Paul A T; Bagdy, Gyorgy


    The acute effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on anxiety-related behaviours were studied using indices of social interaction in Dark Agouti (DA) both drug naive rats and those pretreated with MDMA (15 mg/kg i.p.) 3 weeks earlier. The functional neuroanatomy of these MDMA effects was visualised using 2-deoxyglucose imaging of local cerebral glucose use (LCMRglu), whilst MDMA-induced serotonergic neurotoxicity was measured by radioligand binding with [3H]paroxetine. Acute MDMA alone markedly decreased most typical elements of social interaction but increased adjacent lying, a behaviour that also contains social elements. In animals pre-exposed to MDMA, decreased [3H]paroxetine binding indicated serotonergic terminal depletion, and in these animals significant increases in locomotor activity, exploratory behaviour and aggressive behaviour were found. Both behavioural effects and also the metabolic activation induced by acute MDMA were potentiated in rats previously exposed to the drug. In conclusion, a single dose of MDMA caused marked changes in social behaviour acutely that might be interpreted either as a decrease or increase in anxiety. Three weeks after MDMA a behavioural disinhibition similar to psychomotor agitation, a symptom connected to depression or mania, and a sensitization to the acute effects of MDMA are apparent in both the behavioural and brain metabolic effects of the drug.

  6. Comparative neurochemical profile of 3,4-methylenedioxymethamphetamine and its metabolite alpha-methyldopamine on key targets of MDMA neurotoxicity.

    Escubedo, E; Abad, S; Torres, I; Camarasa, J; Pubill, D


    The neurotoxicity of MDMA or "Ecstasy" in rats is selectively serotonergic, while in mice it is both dopaminergic and serotonergic. MDMA metabolism may play a key role in this neurotoxicity. The function of serotonin and dopamine transporter and the effect of MDMA and its metabolites on them are essential to understand MDMA neurotoxicity. The aim of the present study was to investigate and compare the effects of MDMA and its metabolite alpha-methyldopamine (MeDA) on several molecular targets, mainly the dopamine and serotonin transporter functionality, to provide evidence for the role of this metabolite in the neurotoxicity of MDMA in rodents. MeDA had no affinity for the serotonin transporter but competed with serotonin for its uptake. It had no persistent effects on the functionalism of the serotonin transporter, in contrast to the effect of MDMA. Moreover, MeDA inhibited the uptake of dopamine into the serotonergic terminal and also MAO(B) activity. MeDA inhibited dopamine uptake with a lower IC(50) value than MDMA. After drug washout, the inhibition by MeDA persisted while that of MDMA was significantly reduced. The effect of MDMA on the dopamine transporter is related with dopamine release from vesicular stores, as this inhibition disappeared in reserpine-treated animals. However, the effect of MeDA seems to be a persistent conformational change of this transporter. Moreover, in contrast with MDMA, MeDA did not show affinity for nicotinic receptors, so no effects of MeDA derived from these interactions can be expected. The metabolite reduced cell viability at lower concentrations than MDMA. Apoptosis plays a key role in MDMA induced cellular toxicity but necrosis is the major process involved in MeDA cytotoxicity. We conclude that MeDA could protect against the serotonergic lesion induced by MDMA but potentiate the dopaminergic lesion as a result of the persistent blockade of the dopamine transporter induced this metabolite.

  7. "Ecstasy"-induced toxicity in SH-SY5Y differentiated cells: role of hyperthermia and metabolites.

    Barbosa, Daniel José; Capela, João Paulo; Silva, Renata; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Bastos, Maria Lourdes; Carvalho, Félix


    3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a recreational hallucinogenic drug of abuse known to elicit neurotoxic properties. Hepatic formation of neurotoxic metabolites is thought to play a major role in MDMA-related neurotoxicity, though the mechanisms involved are still unclear. Here, we studied the neurotoxicity mechanisms and stability of MDMA and 6 of its major human metabolites, namely α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA) and their correspondent glutathione (GSH) and N-acetyl-cysteine (NAC) conjugates, under normothermic (37 °C) or hyperthermic conditions (40 °C), using cultured SH-SY5Y differentiated cells. We showed that MDMA metabolites exhibited toxicity to SH-SY5Y differentiated cells, being the GSH and NAC conjugates more toxic than their catecholic precursors and MDMA. Furthermore, whereas the toxicity of the catechol metabolites was potentiated by hyperthermia, NAC-conjugated metabolites revealed higher toxicity under normothermia and GSH-conjugated metabolites-induced toxicity was temperature-independent. Moreover, a time-dependent decrease in extracellular concentration of MDMA metabolites was observed, which was potentiated by hyperthermia. The antioxidant NAC significantly protected against the neurotoxic effects of MDMA metabolites. MDMA metabolites increased intracellular glutathione levels, though depletion in thiol content was observed in MDMA-exposed cells. Finally, the neurotoxic effects induced by the MDMA metabolite N-Me-α-MeDA involved caspase 3 activation. In conclusion, this study evaluated the stability of MDMA metabolites in vitro, and demonstrated that the catechol MDMA metabolites and their GSH and NAC conjugates, rather than MDMA itself, exhibited neurotoxic actions in SH-SY5Y differentiated cells, which were differently affected by hyperthermia, thus highlighting a major role for reactive metabolites and hyperthermia in MDMA's neurotoxicity.

  8. Human Pharmacology of Mephedrone in Comparison with MDMA.

    Papaseit, Esther; Pérez-Mañá, Clara; Mateus, Julián-Andrés; Pujadas, Mitona; Fonseca, Francina; Torrens, Marta; Olesti, Eulàlia; de la Torre, Rafael; Farré, Magí


    Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users.

  9. MDMA induces cardiac contractile dysfunction through autophagy upregulation and lysosome destabilization in rats.

    Shintani-ishida, Kaori; Saka, Kanju; Yamaguchi, Koji; Hayashida, Makiko; Nagai, Hisashi; Takemura, Genzou; Yoshida, Ken-ichi


    The underlying mechanisms of cardiotoxicity of 3,4-methylenedioxymethylamphetamine (MDMA, "ecstasy") abuse are unclear. Autophagy exerts either adaptive or maladaptive effects on cardiac function in various pathological settings, but nothing is known on the role of autophagy in the MDMA cardiotoxicity. Here, we investigated the mechanism through which autophagy may be involved in MDMA-induced cardiac contractile dysfunction. Rats were injected intraperitoneally with MDMA (20mg/kg) or saline. Left ventricular (LV) echocardiography and LV pressure measurement demonstrated reduction of LV systolic contractility 24h after MDMA administration. Western blot analysis showed a time-dependent increase in the levels of microtubule-associated protein light chain 3-II (LC3-II) and cathepsin-D after MDMA administration. Electron microscopy showed the presence of autophagic vacuoles in cardiomyocytes. MDMA upregulated phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) at Thr172, mammalian target of rapamycin (mTOR) at Thr2446, Raptor at Ser792, and Unc51-like kinase (ULK1) at Ser555, suggesting activation of autophagy through the AMPK-mTOR pathway. The effects of autophagic inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) on LC3-II levels indicated that MDMA enhanced autophagosome formation, but attenuated autophagosome clearance. MDMA also induced release of cathepsins into cytosol, and western blotting and electron microscopy showed cardiac troponin I (cTnI) degradation and myofibril damage, respectively. 3-MA, CQ, and a lysosomal inhibitor, E64c, inhibited cTnI proteolysis and improved contractile dysfunction after MDMA administration. In conclusion, MDMA causes lysosome destabilization following activation of the autophagy-lysosomal pathway, through which released lysosomal proteases damage myofibrils and induce LV systolic dysfunction in rat heart.

  10. Major depression: the relative contribution of gender, MDMA, and cannabis use.

    Durdle, Heather; Lundahl, Leslie H; Johanson, Chris-Ellyn; Tancer, Manuel


    Previous research has suggested that 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) users have elevated depressive symptomatology, although it is not clear whether this is due to MDMA or other drug use. This study aimed to investigate the contributions of MDMA and cannabis use to Major Depressive Disorder in MDMA users. A total of 226 MDMA users were studied. Participants (65% male) reported an average number of 35.8 uses of MDMA (SD = 45.6, range = 2-400). Participants were administered a Structured Clinical Interview for DSM-IV. Twenty-six individuals (11.5%) met lifetime criteria for Major Depressive Disorder. High rates of lifetime Cannabis Abuse (30.1%) and Cannabis Dependence (12.4%) were reported. No association was found between number of uses of MDMA and Major Depressive Disorder. Those with lifetime major depression were found, however, to have higher rates of lifetime cannabis use disorder (adjusted OR = 2.40). A logistic regression indicated that lifetime cannabis use disorder, but not MDMA use, was significantly associated with lifetime Major Depressive Disorder. Stratified analyses suggested that for males, neither drug use variable was associated with major depression. For females, a lifetime cannabis use disorder (adjusted OR = 4.99), but not MDMA use, was associated with lifetime Major Depressive Disorder. Results of this study suggest that although MDMA use was not found to be significantly associated with major depression for either gender, a lifetime cannabis use disorder was significantly associated with lifetime major depression for female, but not male, users of MDMA.

  11. Risky Behavior, Ecstasy, and Education

    Callier, Heather H.


    Ecstasy is a risky behavior that continues to be a concern in the education system today. The review of the Ecstasy literature focused on the definition of risky behavior, prevalence, and other basis aspects of Ecstasy; discovering life events that are associated with Ecstasy use, the function of this behavior, interventions for substance abuse,…

  12. Acute psychomotor, memory and subjective effects of MDMA and THC (co-) administration over time in healthy volunteers

    Dumont, G.; Van Hasselt, J.; De Kam, M.; Van Gerven, J.; Touw, D.; Buitelaar, J.; Verkes, R.

    Introduction: In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Cannabis (main active compound D9-tetrahydrocannabinol or THC) is frequently co-used with ecstasy (Parrott et al., 2007).

  13. The acute effects of MDMA and ethanol administration on electrophysiological correlates of performance monitoring in healthy volunteers

    Spronk, D.B.; Dumont, G.J.H.; Verkes, R.J.; Bruijn, E.R. de


    RATIONALE: Knowing how commonly used drugs affect performance monitoring is of great importance, because drug use is often associated with compromised behavioral control. Two of the most commonly used recreational drugs in the western world, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and

  14. Acute psychomotor, memory and subjective effects of MDMA and THC (co-) administration over time in healthy volunteers

    Dumont, G.; Van Hasselt, J.; De Kam, M.; Van Gerven, J.; Touw, D.; Buitelaar, J.; Verkes, R.


    Introduction: In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Cannabis (main active compound D9-tetrahydrocannabinol or THC) is frequently co-used with ecstasy (Parrott et al., 2007). Despit

  15. High Suicide Risk after the Development of Cognitive and Working Memory Deficits Caused by Cannabis, Cocaine and Ecstasy Use

    Pompili, Maurizio; Lester, David; Girardi, Paolo; Tatarelli, Roberto


    We report the case of attempted suicide by a 30-year-old man who had significant cognitive deficits that developed after at least three years of polysubstance use with cannabis, methylenedioxymethamphetamine (MDMA, "ecstasy") and cocaine. The patient reported increasing difficulties in his professional and interpersonal life which may have been…

  16. Trazodone, meta-chlorophenylpiperazine (an hallucinogenic drug and trazodone metabolite), and the hallucinogen trifluoromethylphenylpiperazine cross-react with the EMIT®II ecstasy immunoassay in urine.

    Logan, Barry K; Costantino, Anthony G; Rieders, Eric F; Sanders, David


    A series of patients whose urine screened positive for 3,4-methylenedioxymethamphetamine (MDMA) using a commercial enzyme immunoassay test (Ecstasy EMIT II assay), failed to confirm by substance-specific liquid chromatography-tandem mass spectrometry tests for MDMA. Further evaluation of these urine specimens indicates that they were positive for trazodone and its metabolite meta-chlorophenylpiperazine (m-CPP). Independent tests of standards showed significant crossreactivity on the Ecstasy EMIT II assay with trazodone, m-CPP, and the related recreational drug trifluoromethylphenylpiperazine (TFMPP). This is of further forensic significance because m-CPP is emerging as an illicit recreational drug in its own right or as an adulterant in illicit cocaine and MDMA. The hallucinogen benzylpiperazine was also assessed but found not to cross-react significantly with this assay. Patients taking trazodone may get false-positive results on the urine EMIT test for MDMA.

  17. Paradoxical effects of low dose MDMA on latent inhibition in the rat.

    Nelson, A J D; Thur, K E; Marsden, C A; Cassaday, H J


    The cognitive effects of MDMA ('Ecstasy') are controversial, particularly in the case of acute administration of low doses. Latent inhibition (LI) refers to the reduction in conditioning to a stimulus that has received non-reinforced pre-exposure, an effect typically abolished by amphetamines and enhanced by antipsychotics. LI enhancement has also been shown using the 5-HT reuptake blocker sertraline. In the present study, the effects of MDMA (6 mg/kg, known to increase 5-HT release) were tested using 10 and 40 pre-exposures to produce weak and strong LI in controls, respectively. MDMA (injected twice, prior to pre-exposure and conditioning) significantly enhanced LI in that the effect was clearly demonstrated after only 10 pre-exposures, when it was absent in the saline controls. On its own such a profile of action would be consistent with a procognitive effect of MDMA mediated by increased availability of 5-HT. However, paradoxically the same MDMA treatment reduced LI in the 40 pre-exposures condition. This component of action is likely attributable to MDMA's actions on catecholaminergic systems and is consistent with other evidence of its adverse effects. Moreover, there were small but significant reductions in 5-HT in medial prefrontal cortex (mPFC) and amygdala assayed 7 days post MDMA administration (2 × 6 mg/kg, 24 h apart).

  18. Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): The Influence of Gender and Genetics (CYP2D6, COMT, 5-HTT)

    Ricardo Pardo-Lozano; Magí Farré; Samanta Yubero-Lahoz; Brian O'Mathúna; Marta Torrens; Cristina Mustata; Clara Pérez-Mañá; Klaus Langohr; Elisabet Cuyàs; Marcel lí Carbó; Rafael de la Torre


    The synthetic psychostimulant MDMA (±3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmac...

  19. Verbal memory deficits are correlated with prefrontal hypometabolism in (18FDG PET of recreational MDMA users.

    Oliver G Bosch

    Full Text Available INTRODUCTION: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy" is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu in recreational MDMA users. METHODS: Brain glucose metabolism in rest was assessed using 2-deoxy-2-((18Ffluoro-D-glucose positron emission tomography ((18FDG PET in 19 male recreational users of MDMA and 19 male drug-naïve controls. (18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. RESULTS: As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. CONCLUSIONS: Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users

  20. Single oral doses of (±) 3,4-methylenedioxymethamphetamine ('Ecstasy') produce lasting serotonergic deficits in non-human primates: relationship to plasma drug and metabolite concentrations.

    Mueller, Melanie; Yuan, Jie; McCann, Una D; Hatzidimitriou, George; Ricaurte, George A


    Repeated doses of the popular recreational drug methylenedioxymethamphetamine (MDMA, 'Ecstasy') are known to produce neurotoxic effects on brain serotonin (5-HT) neurons but it is widely believed that typical single oral doses of MDMA are free of neurotoxic risk. Experimental and therapeutic trials with MDMA in humans are underway. The mechanisms by which MDMA produces neurotoxic effects are not understood but drug metabolites have been implicated. The aim of the present study was to assess the neurotoxic potential of a range of clinically relevant single oral doses of MDMA in a non-human primate species that metabolizes MDMA in a manner similar to humans, the squirrel monkey. A secondary objective was to explore the relationship between plasma MDMA and metabolite concentrations and lasting serotonergic deficits. Single oral doses of MDMA produced lasting dose-related serotonergic neurochemical deficits in the brains of squirrel monkeys. Notably, even the lowest dose of MDMA tested (5.7 mg/kg, estimated to be equivalent to 1.6 mg/kg in humans) produced significant effects in some brain regions. Plasma levels of MDMA engendered by neurotoxic doses of MDMA were on the order of those found in humans. Serotonergic neurochemical markers were inversely correlated with plasma concentrations of MDMA, but not with those of its major metabolites, 3,4-dihydroxymethamphetamine and 4-hydroxy-3-methoxymethamphetamine. These results suggest that single oral doses of MDMA in the range of those used by humans pose a neurotoxic risk and implicate the parent compound (MDMA), rather than one of its metabolites, in MDMA-induced 5-HT neural injury.

  1. Meta-analysis of executive functioning in ecstasy/polydrug users.

    Roberts, C A; Jones, A; Montgomery, C


    Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions - updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.

  2. MDMA e seus metabolitos : efeito vascular e toxicidade

    Pimentel, Maria Inês Simões da Silva Travassos


    Dissertação de mestrado em Farmacologia Aplicada, apresentada à Faculdade de Farmácia da Universidade de Coimbra A 3,4 – Metilenodioximetanfetamina (MDMA), comumente designada por ecstasy, é uma droga sintética, ilegal e de elevado potencial de abuso. O seu consumo está particularmente associado a ambientes nocturnos, festas e conceitos musicais específicos, como a música eletrónica ou a cultura dance, numa população essencialmente jovem, com o intuito de aumentar a energia, performance fí...

  3. Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

    Cerretani, D; Bello, S; Cantatore, S; Fiaschi, A I; Montefrancesco, G; Neri, M; Pomara, C; Riezzo, I; Fiore, C; Bonsignore, A; Turillazzi, E; Fineschi, V


    Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the

  4. The external validity of results derived from ecstasy users recruited using purposive sampling strategies.

    Topp, Libby; Barker, Bridget; Degenhardt, Louisa


    This study sought to compare the patterns and correlates of 'recent' and 'regular' ecstasy use estimated on the basis of two datasets generated in 2001 in New South Wales, Australia, from a probability and a non-probability sample. The first was the National Drug Strategy Household Survey (NDSHS), a multistage probability sample of the general population; and the second was the Illicit Drug Reporting System (IDRS) Party Drugs Module, for which regular ecstasy users were recruited using purposive sampling strategies. NDSHS recent ecstasy users (any use in the preceding 12 months) were compared on a range of demographic and drug use variables to NDSHS regular ecstasy users (at least monthly use in the preceding 12 months) and purposively sampled regular ecstasy users (at least monthly use in the preceding 6 months). The demographic characteristics of the three samples were consistent. Among all three, the mean age was approximately 25 years, and a majority (60%) of subjects were male, relatively well-educated, and currently employed or studying. Patterns of ecstasy use were similar among the three samples, although compared to recent users, regular users were likely to report more frequent use of ecstasy. All samples were characterised by extensive polydrug use, although the two samples of regular ecstasy users reported higher rates of other illicit drug use than the sample of recent users. The similarities between the demographic and drug use characteristics of the samples are striking, and suggest that, at least in NSW, purposive sampling that seeks to draw from a wide cross-section of users and to sample a relatively large number of individuals, can give rise to samples of ecstasy users that may be considered sufficiently representative to reasonably warrant the drawing of inferences relating to the entire population. These findings may partially offset concerns that purposive samples of ecstasy users are likely to remain a primary source of ecstasy

  5. Unilatelaral iris plateau syndrome after the use of ecstasy

    Jovanović Predrag


    Full Text Available Bacground. Courmon street name for 3,4-Methylenedioxymethamphetamine (MDMA is ecstasy. This widely abused 'recreational' drug causes both an increased release of monoamine neurotransmitters, including serotonine and dopamine, and an increased reuptake inhibition of serotonin. As a consequence, mydriasis and increased intraocular pressure (IOP in predisposed patients occur. We present herein a rare case of acute increased IOP after use of ecstasy. Case report. A female patient, aged 38 years, visited doctor complaing of a decreased vision acuity and severe pain in the left eye and in the left part of the head. The initial treatment was urgent antiglaucomatous therapy followed by withdrawal of subjective problems of the patient and improvement of objective finding. History taking procedure reveled that just before the onset of the pain the patient had used ecstasy and had had similar 'experience' 6 years ago after cocaine snorting. She had not been to a doctor although she had experienced sporadic migrenous pain. Previous medical records excavation of revealed optic disk (cup-to-dise C/D=06, Bjerum arcuate scotoma and iris plateau with narrow chamber angle (Scheie II- III so the diagnosis was a rare unilateral iris plateau syndrome of the left eye. Although the patient was given some pieces of information about the dangerous and possible deadly consequences of psychoactive substance abuse, she has not continue the treatment. Conclusion. Ecstasy abuse might cause a complete loss of vision, thus medicametous and surgical treatment are obligatory.

  6. The Effect of Ecstasy Administration during Pregnancy on Mice Fetuses

    Y Mostafavi Pour-Manshadi


    Full Text Available Introduction: Ecstasy or 3,4-Methylenedioxymethamphetamine(MDMA is a psychotropic and addictive substance that young people tend to use it to reduce their psychological and social tensions. The purpose of this study was to assess the influence of ecstasy consumption on the fetus of pregnant mice during the second and third weeks of pregnancy. Methods: 20 adult female mice were randomly selected(5 for control group and 15 for experimental group. Two intraperitoneal injections of ecstasy(5mg/Kg was used in the experimental group, on 7th and 14th days of pregnancy, while, in the control group, only distilled water was injected intraperitoneally. On 18th day of pregnancy, mice were placed in separate cages. The condition of palate, skull, external ear, eye, fingers and toes and sindactily, weight, and fertility potentials of newborn mice were studied using stereo microscope. Results: From 163 newborn mice in two groups, no abnormalities were observed in the skull and the external ear. There wasn’t any significant difference between male and female sex ratio between two groups (p=.08. Hypoplasia of the fingers was significantly different between the two groups(p<0.001. The frequency of sindactily was not significantly different between two groups(p=0. 11. Female fertility potential was significantly different between two groups(p<0.001. Conclusion: Adminstration of ecstasy during pregnancy may affect the organogenesis and fertility potential of newborn mice. Therefore, more studies are needed in this regard.

  7. Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective.

    Kim P C Kuypers

    Full Text Available Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT. The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user was predictive of having clinically deficient memory performance compared to a healthy control group.WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions.Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired.The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive

  8. Ecstasy: Intimacy Abridged.

    Schlozman, Steven C.


    Describes the effects and risks of the use of the illegal drug Ecstasy among adolescents to enhance feelings of intimacy. Suggests how teachers can help prevent their students from using the drug. (PKP)

  9. Prenatal exposure to alcohol and 3,4-methylenedioxymethamphetamine (ecstasy) alters adult hippocampal neurogenesis and causes enduring memory deficits.

    Canales, Juan J; Ferrer-Donato, Agueda


    Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.

  10. The preclinical pharmacology of mephedrone; not just MDMA by another name.

    Green, A R; King, M V; Shortall, S E; Fone, K C F


    The substituted β-keto amphetamine mephedrone (4-methylmethcathinone) was banned in the UK in April 2010 but continues to be used recreationally in the UK and elsewhere. Users have compared its psychoactive effects to those of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). This review critically examines the preclinical data on mephedrone that have appeared over the last 2-3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However, both of these responses are of short duration following mephedrone compared with MDMA probably because mephedrone has a short plasma half-life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces a neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. Mephedrone and MDMA both induce release of dopamine and 5-HT in the brain as shown by in vivo and in vitro studies. The effect on 5-HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for the dopamine and 5-HT transporters in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self-administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects, but also differs from other cathinones.

  11. Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat.

    Cox, Brittney M; Shah, Mrudang M; Cichon, Teri; Tancer, Manuel E; Galloway, Matthew P; Thomas, David M; Perrine, Shane A


    Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior.

  12. The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') in healthy volunteers.

    Liechti, M E; Vollenweider, F X


    MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is a widely used recreational drug that produces a state of heightened mood but also cardiovascular and vegetative side-effects. In animals, MDMA releases serotonin and, to a lesser extent, dopamine and norepinephrine. The release of serotonin can be blocked by serotonin uptake inhibitors such as citalopram. It is unknown to what extent this mechanism is also responsible for the physiological side-effects of MDMA seen in humans. We investigated the effect of citalopram pretreatment (40 mg i.v.) on vegetative and cardiovascular effects of MDMA (1.5 mg/kg p.o.) in a double-blind placebo-controlled study in 16 healthy volunteers. MDMA moderately increased blood pressure and heart rate, slightly elevated body temperature and produced a broad range of acute and short-term side-effects. Citalopram reduced all these MDMA-induced physiological changes except for body temperature. These findings suggest that physiological effects of MDMA in humans are partially due to an interaction of MDMA with the serotonin carrier and a subsequent release of serotonin.

  13. Neurotoxicity of Ecstasy metabolites in rat cortical neurons, and influence of hyperthermia.

    Capela, João Paulo; Meisel, Andreas; Abreu, Artur Reis; Branco, Paula Sério; Ferreira, Luísa Maria; Lobo, Ana Maria; Remião, Fernando; Bastos, Maria Lurdes; Carvalho, Félix


    3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a widely abused, psychoactive recreational drug. There is growing evidence that the MDMA neurotoxic profile may be highly dependent on both its hepatic metabolism and body temperature. Metabolism of MDMA involves N-demethylation to 3,4-methylenedioxyamphetamine (MDA), which is also a drug of abuse. MDMA and MDA are O-demethylenated to N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and alpha-methyldopamine (alpha-MeDA), respectively, both of which are catechols that can undergo oxidation to the corresponding ortho-quinones. In the presence of glutathione (GSH), ortho-quinones may be conjugated with GSH to form glutathionyl adducts. In this study, we evaluated the neurotoxicity of MDMA and three of its metabolites obtained by synthesis, N-Me-alpha-MeDA, alpha-MeDA, and 5-(GSH)-alpha-MeDA [5-(glutathion-S-yl)-alpha-methyldopamine] in rat cortical neuronal serum-free cultures under normal (36.5 degrees C) and hyperthermic (40 degrees C) conditions. Cell viability was assessed, and the mechanism of cell death was also evaluated. Our study shows that these metabolites are more neurotoxic [5-(GSH)-alpha-MeDA being the most toxic] than the parent compound MDMA. The neurotoxicity of MDMA metabolites was partially prevented by the antioxidants N-acetylcystein and also, in a minor extent, by alpha-phenyl-N-tert-butyl nitrone. All the tested compounds induced apoptotic cell death in cortical neurons, and their neurotoxic effect was potentiated under hyperthermic conditions. These data suggest that MDMA metabolites, especially under hyperthermic conditions, contribute to MDMA-induced neurotoxicity.

  14. Prenatal MDMA exposure delays postnatal development in the rat: a preliminary study.

    Heuland, Emilie; Germaux, Marie-Aure; Galineau, Laurent; Chalon, Sylvie; Belzung, Catherine


    3,4-methylenedioxymethamphetamine or MDMA (ecstasy) is a synthetic illicit drug which is widely consumed throughout the world. Drug abuse during pregnancy may have an impairing effect on the progeny of drug-abusing mothers. The purpose of the present study was to assess the effect of prenatal MDMA exposure on the progeny development, using a rat model. Pregnant animals were injected daily with MDMA (10 mg/kg) between the 13th and 20th days of gestation. Male and female pups were then tested throughout the lactation period on the appearance and improvement of physical and sensory motor parameters. Appearance of some physical features (eyes opening and incisor eruption) and neurological reflexes as well as improving performances in negative geotaxis, gait and inclined board tests were delayed in pups prenatally exposed to MDMA compared to saline-treated pups. In contrast, functions that are necessary for survival such as forelimb reflex (that enables suckling) were present in both groups. At four weeks of age, MDMA animals recovered to normal level in all studied parameters. The delay in physical and neurological reflex development could be interpreted as alterations in maturation of some neuronal circuitries induced by prenatal MDMA exposure.

  15. Anestesia e o usuário de Ecstasy Anestesia y el usuario de Ecstasy Anesthesia and the Ecstasy user

    Eduardo Toshiyuki Moro


    Full Text Available JUSTIFICATIVA E OBJETIVOS: Nos últimos anos o número de novos usuários de agentes ilícitos tem aumentado de forma significativa em todo o mundo. A maconha e a cocaína, além do álcool e do tabaco, têm sido os agentes citados com freqüência, porém houve um aumento significativo de usuários de outros agentes psicoestimulantes ou alucinógenos, como o Ecstasy, o GHB, o LSD e a metanfetamina, empregados com o objetivo de intensificar as experiências sociais. O objetivo do presente artigo foi discutir a apresentação clínica, os efeitos deletérios e as potenciais interações com o ato anestésico no paciente cirúrgico usuário desses agentes ilícitos. CONTEÚDO: O artigo discute os mecanismos de ação, a apresentação clínica, os efeitos deletérios e as possíveis repercussões observadas durante a anestesia no usuário de MDMA (3,4-metilenodioximetanfetamina, também conhecido como Ecstasy. CONCLUSÕES: A apresentação clínica e os efeitos deletérios provocados pelo 3,4-metilenodioximetanfetamina (Ecstasy, assim como potenciais interações com o ato anestésico devem ser do conhecimento do anestesiologista, pois em muitas situações esses usuários serão submetidos a intervenções cirúrgicas de emergência, ou mesmo eletivas.JUSTIFICATIVA Y OBJETIVOS: En los últimos años el número de nuevos usuarios de drogas ilícitas ha aumentado de forma significativa en todo el mundo. La marihuana y la cocaína, además del alcohol y del tabaco, han sido las drogas citadas frecuentemente, sin embargo, hubo un aumento significativo de usuarios de otros agentes psicoestimulantes o alucinógenos, como el Ecstasy, el GHB, el LSD y la metanfetamina, empleados con el objetivo de intensificar las experiencias sociales. El objetivo del presente artículo fue el de traer a colación la presentación clínica, los efectos destructivos y las potenciales interacciones con el acto anestésico en el paciente quirúrgico usuario de esas drogas

  16. Autophagy activation is involved in 3,4-methylenedioxymethamphetamine ('ecstasy'--induced neurotoxicity in cultured cortical neurons.

    I-Hsun Li

    Full Text Available Autophagic (type II cell death, characterized by the massive accumulation of autophagic vacuoles in the cytoplasm of cells, has been suggested to play pathogenetic roles in cerebral ischemia, brain trauma, and neurodegenerative disorders. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy is an illicit drug causing long-term neurotoxicity in the brain. Apoptotic (type I and necrotic (type III cell death have been implicated in MDMA-induced neurotoxicity, while the role of autophagy in MDMA-elicited neurotoxicity has not been investigated. The present study aimed to evaluate the occurrence and contribution of autophagy to neurotoxicity in cultured rat cortical neurons challenged with MDMA. Autophagy activation was monitored by expression of microtubule-associated protein 1 light chain 3 (LC3; an autophagic marker using immunofluorescence and western blot analysis. Here, we demonstrate that MDMA exposure induced monodansylcadaverine (MDC- and LC3B-densely stained autophagosome formation and increased conversion of LC3B-I to LC3B-II, coinciding with the neurodegenerative phase of MDMA challenge. Autophagy inhibitor 3-methyladenine (3-MA pretreatment significantly attenuated MDMA-induced autophagosome accumulation, LC3B-II expression, and ameliorated MDMA-triggered neurite damage and neuronal death. In contrast, enhanced autophagy flux by rapamycin or impaired autophagosome clearance by bafilomycin A1 led to more autophagosome accumulation in neurons and aggravated neurite degeneration, indicating that excessive autophagosome accumulation contributes to MDMA-induced neurotoxicity. Furthermore, MDMA induced phosphorylation of AMP-activated protein kinase (AMPK and its downstream unc-51-like kinase 1 (ULK1, suggesting the AMPK/ULK1 signaling pathway might be involved in MDMA-induced autophagy activation.

  17. Lhermitte's sign, electric shock sensations and high dose ecstasy consumption: preliminary findings.

    Boland, B; Mitcheson, L; Wolff, K


    The objectives of this study were to perform a preliminary investigation into the nature of electric shock-like experiences reported in association with the use of ecstasy tablets thought to contain methylenedioxymethamphetamines (MDMA). This included exploration of reports of electric shock-like experiences from the user's perspectives and identification of other variables that may be associated with their development. Furthermore we aimed to examine whether the well-recognised electric shock-like symptom, Lhermitte's sign (LS), is associated with ecstasy tablet use in some drug users. A single measure, cross-sectional survey was used incorporating mixed qualitative and quantitative methodology. A select group of ecstasy users (n = 35) recruited through a dance, music and lifestyle magazine completed a telephone interview. Lifetime prevalence of LS in the study population was 18% (n = 6). Development of LS was associated with use of more ecstasy tablets before a typical incident. This study indicates a relationship may exist between the use of ecstasy tablets and LS. The relationship may be dose dependent. The majority of the study population used other substances including alcohol when experiencing electrical shock sensations. LS may explain only a proportion of all electrical shock experiences among ecstasy users.

  18. Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a naturalistic study.

    Stewart, L H; Ferguson, B; Morgan, C J A; Swaboda, N; Jones, L; Fenton, R; Wall, M B; Curran, H V


    Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') can promote pro-social effects which may alter interpersonal perceptions. To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people's faces and co-operative behaviours. An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings. Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3. Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy. © The Author(s) 2014.

  19. MDMA impairs mitochondrial neuronal trafficking in a Tau- and Mitofusin2/Drp1-dependent manner.

    Barbosa, Daniel José; Serrat, Román; Mirra, Serena; Quevedo, Martí; Gómez de Barreda, Elena; Avila, Jesús; Fernandes, Eduarda; Bastos, Maria de Lourdes; Capela, João Paulo; Carvalho, Félix; Soriano, Eduardo


    Identification of the mechanisms by which drugs of abuse cause neuronal dysfunction is essential for understanding the biological bases of their acute and long-lasting effects in the brain. Here, we performed real-time functional experiments of axonal transport of mitochondria to explore the role of in situ mitochondrial dysfunction in 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy")-related brain actions. We showed that MDMA dramatically reduced mitochondrial trafficking in hippocampal neurons in a Tau-dependent manner, in which glycogen synthase kinase 3β activity was implicated. Furthermore, we found that these trafficking abnormalities were rescued by over-expression of Mitofusin2 and dynamin-related protein 1, but not of Miro1. Given the relevance of mitochondrial targeting for neuronal function and neurotransmission, our data underscore a novel mechanism of action of MDMA that may contribute to our understanding of how this drug of abuse alters neuronal functioning.

  20. Neuroprotective properties of melissa officinalis L. Extract against ecstasy-induced neurotoxicity.

    Hassanzadeh, Gholamreza; Pasbakhsh, Parichehr; Akbari, Mohammad; Shokri, Saeed; Ghahremani, Mohammadhosein; Amin, Gholamreza; Kashani, Iraj; Azami Tameh, Abolfazl


    The aim of the present study was to investigate the neuroprotective effects of Melissa officinalis, a major antioxidant plant, against neuron toxicity in hippocampal primary culture induced by 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy, one of the most abused drugs, which causes neurotoxicity. 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to assess mitochondrial activity, reflecting cell survival. Caspase-3 activity assay and Hoechst / propiedium iodide (PI) staining were done to show apoptotic cell death. A high dose of ecstasy caused profound mitochondrial dysfunction, around 40% less than the control value, and increased apoptotic neuronal death to around 35% more than the control value in hippocampal neuronal culture. Co-treatment with Melissa officinalis significantly reversed these damages to around 15% and 20% respectively of the MDMA alone group, and provided protection against MDMA-induced mitochondrial dysfunction and apoptosis in neurons. Melissa officinalis has revealed neuroprotective effects against apoptosis induced by MDMA in the primary neurons of hippocampal culture, which could be due to its free radical scavenging properties and monoamine oxidase (MAO) inhibitory effects.

  1. Polydipsia as another mechanism of hyponatremia after 'ecstasy' (3,4 methyldioxymethamphetamine) ingestion.

    Brvar, Miran; Kozelj, Gordana; Osredkar, Josko; Mozina, Martin; Gricar, Marko; Bunc, Matjaz


    Acute symptomatic hyponatremia after ecstasy (3,4 methyldioxymethamphetamine; MDMA) ingestion is well documented and has been attributed to the syndrome of inappropriate antidiuretic hormone (SIADH). We report the case of an 18-year-old woman who took five tablets of ecstasy in a suicide attempt and drank 1700 ml water at the Emergency Department (ED). The laboratory findings obtained 5 h after ingestion showed a serum sodium concentration of 130 mmol/l, plasma osmolality of 264 mOsm/kg, urinary osmolality of 335 mOsm/kg and natriuresis of 101 mmol/l. The plasma arginine vasopressin level by radioimmunoassay was 33.7 pmol/l 5 h after ingestion. A gas chromatography-mass spectrometry assay confirmed MDMA in blood samples, with serum concentrations of 0.87 mg/l on arrival. This case report strongly suggests that MDMA reduces serum sodium levels through the dual pathways of SIADH and polydipsia. Accordingly, we believe that hyponatremia may be prevented in ED patients after MDMA ingestion by the early restriction of water intake.

  2. Electrochemical oxidation of amphetamine-like drugs and application to electroanalysis of ecstasy in human serum.

    Garrido, E M P J; Garrido, J M P J; Milhazes, N; Borges, F; Oliveira-Brett, A M


    Amphetamine and amphetamine-like drugs are popular recreational drugs of abuse because they are powerful stimulants of the central nervous system. Due to a dramatic increase in the abuse of methylenedioxylated derivatives, individually and/or in a mixture, and to the incoherent and contradictory interpretation of the electrochemical data available on this subject, a comprehensive study of the redox properties of amphetamine-like drugs was accomplished. The oxidative behaviour of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) was studied in different buffer systems by cyclic, differential pulse and square-wave voltammetry using a glassy carbon electrode. A quantitative electroanalytical method was developed and successfully applied to the determination of MDMA in seized samples and in human serum. Validation parameters, such as sensitivity, precision and accuracy, were evaluated. The results found using the developed electroanalytical methodology enabled to gather some information about the content and amount of MDMA present in ecstasy tablets found in Portugal. Moreover, the data found in this study outlook the possibility of using the voltammetric methods to investigate the potential harmful effects of interaction between drugs such as MDMA and methamphetamine and other substances often used together in ecstasy tablets.

  3. Ecstasy : [poems] / Marie Under

    Under, Marie, 1883-1980


    Autori lühitutvustus lk. 218. Sisu: Ecstasy ; Summer memory ; Night ; Tree with birds / transl. by W. K. Matthews ; How could I sleep ; With myself ; Evening ; The white page ; Accounts to render / transl. by Leonard Fox. Orig.: Ekstaas ; Suvine mälestus ; Öö ; Puu lindudega ; Kuis võiksin magada ; Endaga ; Õhtu ; Valge leht ; Aruand

  4. Ecstasy : [poems] / Marie Under

    Under, Marie, 1883-1980


    Autori lühitutvustus lk. 218. Sisu: Ecstasy ; Summer memory ; Night ; Tree with birds / transl. by W. K. Matthews ; How could I sleep ; With myself ; Evening ; The white page ; Accounts to render / transl. by Leonard Fox. Orig.: Ekstaas ; Suvine mälestus ; Öö ; Puu lindudega ; Kuis võiksin magada ; Endaga ; Õhtu ; Valge leht ; Aruand

  5. Ecstasy and vision

    Anders Hultgård


    Full Text Available In this paper we shall present some observations on the role played by ecstasy in the activity of the seer, as he emerges in ancient Jewish and Iranian texts. In the Jewish religious literature of the Hellenistic-Roman period, visions are described on almost every page, and visions were the most important means of divine revelation. Specific techniques for inducing the ecstatic state are not recorded in the Jewish sources. Some elements in the pattern leading up to the vision may be interpreted as parts of a method for inducing the final ecstasy; i.e. fasting and prayer. The Iranian material shows clearly the importance of ecstasy in the activity of the seer. The ecstatic seeing also means that the visionary shares with Ahura Mazda a divine quality, the "wisdom of omniscience". The granting of the "wisdom of omniscience" appears as a temporary and it conveys to the visionary a supernatural seeing. There is evidence to suggest that chanting was an important method of inducing ecstasy within the early Zoroastrian community. We do not find in the Jewish material a clear correspondence to the Iranian notion of "omniscient wisdom".

  6. Ecstasy: commodity or disease?

    Agar, Michael; Reisinger, Heather Schacht


    This article evaluates past work on heroin and crack cocaine epidemics by comparing it with the increase in Ecstasy use in the late 1990s. First of all, the authors make the case that there was, in fact, a dramatic increase in Ecstasy use in the late 1990s. Following that is a review of the rise and fall of several different Ecstasy scenes beginning in the 1960s. The most recent rise, in the late 1990s, requires a broadening of the theory of epidemics to include longer historical waves of change, so we do that by reviewing work on post World War II trends in social disconnection and consumerism. We then shift to a marketing rather than a public health framework and look at the nature of the Ecstasy "product," both its good and bad characteristics. Finally, we describe the narrative mechanism, developed in our earlier work, that plausibly explains why use rose when it did, given the needs of the market. The article concludes by discussing the changes this case motivates for our theory, particularly in light of globalized and normalized drug use that at the moment appears to be the current context for illicit drug use.

  7. Ecstasy and mysticism

    Hans Hof


    Full Text Available Phenomena such as ecstasy and mysticism display both psychological and physical features. The purpose of this paper is finding and understanding the structures in human consciousness which characterise the experience of certain kinds of ecstasy. The context in which this task is performed is an outline of fundamental changes in consciousness brought about by those methods of meditation which, under optimal conditions, give rise to mystical experience.. What makes ecstasy ecstasy or mysticism mysticism is their psychologically describable features and not the physical ones. How does one go about an experimental investigation of phenomena whose main features are to be found in subjective experience? How can one find intersubjective criteria? A useful approach in obtaining an answer to these questions is shown by the experiences afforded us through the so called "meditation". By drawing a map of the changes in a person's self-experience that can be effected by a body-centered technique of meditation, the structures of consciousness that are characteristic of ecstatic and mystical experiences can be identified. This method can be considered as a phenomenological investigation of consciousness-related phenomena. Absolute ecstasy means the experience of a state of consciousness which, it is claimed, is able to cause experience of a synthesis of a transcendent and a non-transcendent dimension of reality. It is easy to realise that a necessary condition for an understanding of statements claiming experience of a synthesis between transcendence and immanence is the psychological understanding of the state of consciousness in which the claimed experience of the synthesis was made. It is only in the context of a psychological understanding of the state of consciousness which is called absolute nothingness that the mystics' claims of a synthesis or an integrated unity of empirical reality and what transcends it becomes meaningful.

  8. The Prosocial Effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled Studies in Humans and Laboratory Animals

    Kamilar-Britt, Philip; Bedi, Gillinder


    Users of ±3,4-Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) report prosocial effects such as sociability and empathy. Supporting these apparently unique social effects, data from controlled laboratory studies indicate that MDMA alters social feelings, information processing, and behavior in humans, and social behavior in rodents. Here, we review this growing body of evidence. In rodents, MDMA increases passive prosocial behavior (adjacent lying) and social reward while decreasing aggression, effects that may involve serotonin 1A receptor mediated oxytocin release interacting with vasopressin receptor 1A. In humans, MDMA increases plasma oxytocin and produces feelings of social affiliation. It decreases identification of negative facial expressions (cognitive empathy) and blunts responses to social rejection, while enhancing responses to others’ positive emotions (emotional empathy) and increasing social approach. Thus, consistent with drug folklore, laboratory administration of MDMA robustly alters social processing in humans and increases social approach in humans and animals. Effects are consistent with increased sociability, with mixed evidence about enhanced empathy. These neurobiologically-complex prosocial effects likely motivate recreational ecstasy use. PMID:26408071

  9. Effects of methylphenidate and MDMA on appraisal of erotic stimuli and intimate relationships.

    Schmid, Yasmin; Hysek, Cédric M; Preller, Katrin H; Bosch, Oliver G; Bilderbeck, Amy C; Rogers, Robert D; Quednow, Boris B; Liechti, Matthias E


    Methylphenidate mainly enhances dopamine neurotransmission whereas 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") mainly enhances serotonin neurotransmission. However, both drugs also induce a weaker increase of cerebral noradrenaline exerting sympathomimetic properties. Dopaminergic psychostimulants are reported to increase sexual drive, while serotonergic drugs typically impair sexual arousal and functions. Additionally, serotonin has also been shown to modulate cognitive perception of romantic relationships. Whether methylphenidate or MDMA alter sexual arousal or cognitive appraisal of intimate relationships is not known. Thus, we evaluated effects of methylphenidate (40 mg) and MDMA (75 mg) on subjective sexual arousal by viewing erotic pictures and on perception of romantic relationships of unknown couples in a double-blind, randomized, placebo-controlled, crossover study in 30 healthy adults. Methylphenidate, but not MDMA, increased ratings of sexual arousal for explicit sexual stimuli. The participants also sought to increase the presentation time of implicit sexual stimuli by button press after methylphenidate treatment compared with placebo. Plasma levels of testosterone, estrogen, and progesterone were not associated with sexual arousal ratings. Neither MDMA nor methylphenidate altered appraisal of romantic relationships of others. The findings indicate that pharmacological stimulation of dopaminergic but not of serotonergic neurotransmission enhances sexual drive. Whether sexual perception is altered in subjects misusing methylphenidate e.g., for cognitive enhancement or as treatment for attention deficit hyperactivity disorder is of high interest and warrants further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  10. Ecstasy: It's the Rave

    Dennis, Dixie; Ballard, Michael


    National statistics reveal an alarming trend concerning the use of 3,4-methylenedioxymethamphetamine, which is better known as ecstasy. Results from the Monitoring the Future survey of 50,000 secondary youth reveal that use among 8th graders rose to 3.1%, 5.4% among 10th graders, and 8.2% among 12th graders. High school faculty and staff must be…

  11. Implications of mechanism-based inhibition of CYP2D6 for the pharmacokinetics and toxicity of MDMA.

    Yang, Jiansong; Jamei, Masoud; Heydari, Amir; Yeo, Karen R; de la Torre, Rafael; Farré, Magí; Tucker, Geoffrey T; Rostami-Hodjegan, Amin


    The aim of this study was to model the in vivo kinetic consequences of mechanism-based inhibition (MBI) of CYP2D6 by 3,4 methylenedioxymethamphetamine (MDMA, ecstasy). A model with physiologically-based components of drug metabolism was developed, taking account of change in the hepatic content of active CYP2D6 due to MBI by MDMA. Based on the in vitro information, plasma concentration time profiles of MDMA after various doses were computed and compared with reported observations. The analysis suggested that a typical recreational MDMA dose could inactivate most hepatic CYP2D6 within an hour, and the return to a basal level of CYP2D6 could take at least 10 days. Thus, the genetic polymorphism of CYP2D6 and coadministration of CYP2D6 inhibitors may have less impact on MDMA pharmacokinetics and the risk of acute toxicity than previously thought. This is consistent with clinical observations that indicate no obvious link between inherited CYP2D6 deficiency and acute MDMA intoxication.

  12. MDMA and PTSD treatment: "PTSD: From novel pathophysiology to innovative therapeutics".

    Sessa, Ben


    There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment-resistant PTSD. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  13. A fluorescent probe for ecstasy.

    Masseroni, D; Biavardi, E; Genovese, D; Rampazzo, E; Prodi, L; Dalcanale, E


    A nanostructure formed by the insertion in silica nanoparticles of a pyrene-derivatized cavitand, which is able to specifically recognize ecstasy in water, is presented. The absence of effects from interferents and an efficient electron transfer process occurring after complexation of ecstasy, makes this system an efficient fluorescent probe for this popular drug.

  14. Spontaneous pneumomediastinum and Ecstasy abuse.

    Pittman, J A; Pounsford, J C


    Ecstasy is an illegal recreationally used drug. A case of a young woman who had taken this drug and was found to have a spontaneous pneumomediastinum is reported. The association of spontaneous pneumomediastinum with drug abuse is discussed. The possible mechanism for this complication of Ecstasy, which has not been previously reported, is discussed.

  15. Prevalence Rate of Using ٍEcstasy among Medical Sciences Students in Urmia University in 2007

    Sh. Miri Ghaffarzadeh


    Full Text Available Introduction & Objective: The present study aims to achieve a comprehensive depiction of ecstasy consumption among the students of Urmia University of medical sciences in 2007.Materials & Methods: Totally 950 students were surveyed in this cross-sectional descriptive study. A census was used as a sampling method. A self-report questionnaire regarding demographic details and ecstasy consumption was completed by students. Data was stored in a database and then was analyzed through descriptive tests by SPSS software. Chi square test was used to determine the correlation coefficient.Results: There were 798 subjects of all target population who had never used this drug. However, 132 subjects (18 regularly, 56 occasionally for fun and 58 at least once consumed ecstasy pills. Thus the point prevalence of ecstasy consumption among the students was 14.19 percent. There were 232 subjects who had never heard of the term “ecstasy". Instead, the knowledge source of the rest about ecstasy was books (116 subject, internet (56 subjects, mass media (489 subjects, friends (28 subjects, and family (2 subjects. A significant relation was observed between ecstasy consumption and other variables (parents' education, residence in student campus, attending parties, smoking, canabis and opium consumption. Conclusion: Results of this study revealed that the point prevalence of ecstasy pills consumption among university students was 14.19% that raises the need for purposive intervention and the necessity of planning to prevent and decrease this phenomenon.(Sci J Hamadan Univ Med Sci 2012;18(4:67-72

  16. Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana.

    Schierenbeck, Thomas; Riemann, Dieter; Berger, Mathias; Hornyak, Magdolna


    The illicit recreational drugs cocaine, ecstasy and marijuana have pronounced effects upon sleep. Administration of cocaine increases wakefulness and suppresses REM sleep. Acute cocaine withdrawal is often associated with sleep disturbances and unpleasant dreams. Studies have revealed that polysomnographically assessed sleep parameters deteriorate even further during sustained abstinence, although patients report that sleep quality remains unchanged or improves. This deterioration of objective sleep measures is associated with a worsening in sleep-related cognitive performance. Like cocaine, 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a substance with arousing properties. Heavy MDMA consumption is often associated with persistent sleep disturbances. Polysomnography (PSG) studies have demonstrated altered sleep architecture in abstinent heavy MDMA users. Smoked marijuana and oral Delta-9-tetrahydrocannabinol (THC) reduce REM sleep. Moreover, acute administration of cannabis appears to facilitate falling asleep and to increase Stage 4 sleep. Difficulty sleeping and strange dreams are among the most consistently reported symptoms of acute and subacute cannabis withdrawal. Longer sleep onset latency, reduced slow wave sleep and a REM rebound can be observed. Prospective studies are needed in order to verify whether sleep disturbances during cocaine and cannabis withdrawal predict treatment outcome.

  17. Analysis of ecstasy tablets using capillary electrophoresis with capacitively coupled contactless conductivity detection.

    Porto, Suely K S S; Nogueira, Thiago; Blanes, Lucas; Doble, Philip; Sabino, Bruno D; do Lago, Claudimir L; Angnes, Lúcio


    A method for the identification of 3,4-methylenedioxymethamphetamine (MDMA) and meta-chlorophenylpiperazine (mCPP) was developed employing capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C(4) D). Sample extraction, separation, and detection of "Ecstasy" tablets were performed in <10 min without sample derivatization. The separation electrolyte was 20 mm TAPS/Lithium, pH 8.7. Average minimal detectable amounts for MDMA and mCPP were 0.04 mg/tablet, several orders of magnitude lower than the minimum amount encountered in a tablet. Seven different Ecstasy tablets seized in Rio de Janeiro, Brazil, were analyzed by CE-C(4) D and compared against routine gas chromatography-mass spectrometry (GC-MS). The CE method demonstrated sufficient selectivity to discriminate the two target drugs, MDMA and mCPP, from the other drugs present in seizures, namely amphepramone, fenproporex, caffeine, lidocaine, and cocaine. Separation was performed in <90 sec. The advantages of using C(4) D instead of traditional CE-UV methods for in-field analysis are also discussed.

  18. Chronic exposure to MDMA (ecstasyinduces DNA damage, impairs functional antioxidant cellular defenses, enhances the lipid peroxidation process and alters testes histopathology in male rat

    Nadia Gamal Zaki, ** Laila Abdel Kawy


    Full Text Available Background : 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy" is consumed mainly by young population. For this reason, it is especially relevant to take into consideration the effects on the reproductive system. The influence of MDMA on the fertility and reproduction of the male rat was assessed in this study. Material and methods: MDMA was administered orally at 0 mg/kg (control, 10 and 30 mg/kg to male rats for 15,30,45 consecutive days followed by 15 days withdrawal. Hormonal, biochemical, histological and testicular were evaluated in the rats. The present study aimed to investigate if daily oral administration of ecstasy at low doses(10mg for 45 days has any deleterious effects on reproductive functions of male rats. Animals were randomly divided into four groups of ten rats each, assigned as control rats, or(0mg ecstasy, rats treated with 10mg ecstasy for, (15,30,45 days, rats treated with 30mg/kg body weight ecstasy for(,15,30,45days by oral gavage. The third group(45 days was followed by 15 withdrawal period(W15. Results: The activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in testicular homogenate were decreased while the levels of lipid peroxidation increased significantly in the treated rats as compared with the corresponding group of control animals. In group 30mg, only, arachidonic acid was significantly elevated in the testicular homogenate while linoleic acid was decresed when compared to control. Testis DNA fragmentation was observed in 30mg group, but not It is concluded that low doses of ecstasy exposure(10 mg/Kg had moderate detrimental effects on reproductive organ system and more severe effects are likely to be observed at higher dose levels. These results indicate that ecstasy is directly toxic to primary Leydig cells, and that the decreased percentage of normal cells and the increased level of DNA damage in ecstasy -exposed Leydig cells may be responsible for

  19. Rewarding effects of the optical isomers of 3,4-methylenedioxy-methylamphetamine ('Ecstasy') and 3,4-methylenedioxy-ethylamphetamine ('Eve') measured by conditioned place preference in rats.

    Meyer, Anja; Mayerhofer, Andreas; Kovar, Karl-Artur; Schmidt, Werner J


    3,4-methylenedioxy-methylamphetamine (MDMA) ('Ecstasy') and its analogue 3,4-methylenedioxy-methylamphetamine (MDE) ('Eve') are well known illicit street drugs mainly abused by young people. In spite of the actual research going on, the classification of their abuse potential remains unclear. Since secondary reinforcers are the main factors responsible for craving and relapse, the aim of our study was to assess the potency of MDMA and MDE in a second order reinforcement paradigm, i.e. conditioned place preference (CPP). For the general assessment of our study conditions, we compared MDMA with amphetamine. Unexpectedly, no significant CPP for MDMA was found in contrast to amphetamine. Detailed analysis of current literature led us to the working hypothesis that social environment is crucial for the development of CPP. In a subsequent experiment we tested the influence of housing conditions on CPP using MDMA and demonstrated that isolated animals show significant CPP compared to group-housed ones. In order to better understand the rewarding mechanisms of Ecstasy-derivatives, we tested both the racemic drugs and the pure isomers in the CPP paradigm. Both MDMA's optical isomers and racemic MDMA showed significant CPP without notable differences, while MDE and its isomers completely failed to show any significant CPP. In conclusion, the mechanism by which MDMA induces addiction is much more complicated than assumed so far and more pronounced in isolated animals. The fact that both optical isomers of MDMA led to CPP implies that at least two pathways by which MDMA induces craving behaviour exist.

  20. Evaluation of the Ecstasy influence on tramadol and its main metabolite plasma concentration in rats.

    Jamali, Bardia; Sheikholeslami, Behjat; Hosseinzadeh Ardakani, Yalda; Lavasani, Hoda; Rouini, Mohammad-Reza


    Tramadol is prone to be abused alone, or in combination with 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). It was reported that 95% of people with a history of substance abuse in the United States used tramadol in 2004. According to the WHO report in 2016, there was a growing number of tramadol abusers alone or in combination with psychoactive substances such as MDMA in particular in some Middle East countries. Higher concentrations of tramadol in plasma may lead to adverse drug reactions or lethal intoxication. In this study, the effect of MDMA on the pharmacokinetics of tramadol was examined in male rats. The effect of MDMA on Tmax, Cmax, area under the curve, elimination rate, and half-life of tramadol and its metabolites was examined. Two control and two treatment groups were designed. The treatment groups received MDMA 18 h before the administration of tramadol. Jugular vein blood samples were analyzed by high-performance liquid chromatography with fluorescent detector to determine the concentrations of tramadol and its metabolites. Independent-sample t-test was used to define the differences between pharmacokinetic parameters of control and treatment groups. When tramadol administered intraperitoneally, the absorption rate of this drug was reduced, and a lower Cmax (40%) with longer Tmax (eight-fold) was achieved. MDMA exerted greater inhibitory effects on cytochrome P450 3A4 (CYP3A4) than on cytochrome P450 2D6 (CYP2D6). The M2 metabolite ratio was reduced by half, and because of the inhibition of M2 production, the M1 plasma concentration slightly increased. According to the obtained data, MDMA treatment affected the absorption, distribution and metabolism phases of tramadol. This treatment increased the concentration of tramadol if administered intravenously and can latent the absorption of tramadol in oral route. However, MDMA was introduced as CYP2D6 inhibitor; in this study, MDMA inhibited CYP3A4 isoenzymes as well. This finding is important for

  1. [Death after the intake of amphetamine/ecstasy: two case reports].

    Wöllner, Kirsten; Stockhausen, Sarah; Mußhoff, Frank; Madea, Burkhard


    Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy) have become recreational drugs in German discotheques because of their euphoric and mood-brightening effects. However, their consumption involves considerable risks, which may even be lethal under certain circumstances. A 19-year-old man was taken to a university hospital for suspected intoxication with a narcotic drug, where he died the next day. As cause of death "fulminant liver failure" was diagnosed. In blood from the femoral vein, MDMA was found in a concentration of 4.27 mg/l. Histological examination showed acute necrosis of the liver and parenchymatous bleeding. The second case is that of a 39-year-old man who collapsed at his workplace and died in hospital shortly afterwards. In his rucksack, a small bag with 1.6 g of amphetamine was found. Analysis of blood from the femoral vein showed an amphetamine concentration of 1.08 mg/l.

  2. Neurotoxic thioether adducts of 3,4-methylenedioxymethamphetamine identified in human urine after ecstasy ingestion.

    Perfetti, Ximena; O'Mathúna, Brian; Pizarro, Nieves; Cuyàs, Elisabet; Khymenets, Olha; Almeida, Bruno; Pellegrini, Manuela; Pichini, Simona; Lau, Serrine S; Monks, Terrence J; Farré, Magí; Pascual, Jose Antonio; Joglar, Jesús; de la Torre, Rafael


    3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a widely misused synthetic amphetamine derivative and a serotonergic neurotoxicant in animal models and possibly humans. The underlying mechanism of neurotoxicity involves the formation of reactive oxygen species although their source remains unclear. It has been postulated that MDMA-induced neurotoxicity is mediated via the formation of bioreactive metabolites. In particular, the primary catechol metabolites, 3,4-dihydroxymethamphetamine (HHMA) and 3,4-dihydroxyamphetamine (HHA), subsequently cause the formation of glutathione and N-acetylcysteine conjugates, which retain the ability to redox cycle and are serotonergic neurotoxicants in rats. Although the presence of such metabolites has been recently demonstrated in rat brain microdialysate, their formation in humans has not been reported. The present study describes the detection of 5-(N-acetylcystein-S-yl)-3,4-dihydroxymethamphetamine (N-Ac-5-Cys-HHMA) and 5-(N-acetylcystein-S-yl)-3,4-dihydroxyamphetamine (N-Ac-5-Cys-HHA) in human urine of 15 recreational users of MDMA (1.5 mg/kg) in a controlled setting. The results reveal that in the first 4 h after MDMA ingestion approximately 0.002% of the administered dose was recovered as thioether adducts. Genetic polymorphisms in CYP2D6 and catechol-O-methyltransferase expression, the combination of which are major determinants of steady-state levels of HHMA and 4-hydroxy-3-methoxyamphetamine, probably explain the interindividual variability seen in the recovery of N-Ac-5-Cys-HHMA and N-Ac-5-Cys-HHA. In summary, the formation of neurotoxic thioether adducts of MDMA has been demonstrated for the first time in humans. The findings lend weight to the hypothesis that the bioactivation of MDMA to neurotoxic metabolites is a relevant pathway to neurotoxicity in humans.

  3. The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations.

    Barbosa, Daniel José; Serrat, Romàn; Mirra, Serena; Quevedo, Martí; de Barreda, Elena Goméz; Àvila, Jesús; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Lourdes Bastos, Maria de; Capela, João Paulo; Soriano, Eduardo; Carvalho, Félix


    3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca(2+) homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury.

  4. The mixture of "ecstasy" and its metabolites is toxic to human SH-SY5Y differentiated cells at in vivo relevant concentrations.

    Barbosa, Daniel José; Capela, João Paulo; Silva, Renata; Vilas-Boas, Vânia; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Bastos, Maria de Lourdes; Carvalho, Félix


    The neurotoxicity of "ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) is thought to involve hepatic metabolism, though its real contribution is not completely understood. Most in vitro neurotoxicity studies concern isolated exposures of MDMA or its metabolites, at high concentrations, not considering their mixture, as expected in vivo. Therefore, our postulate is that combined deleterious effects of MDMA and its metabolites, at low micromolar concentrations that may be attained into the brain, may elicit neurotoxicity. Using human SH-SY5Y differentiated cells as dopaminergic neuronal model, we studied the neurotoxicity of MDMA and its MDMA metabolites α-methyldopamine and N-methyl-α-methyldopamine and their correspondent glutathione and N-acetylcysteine monoconjugates, under isolated exposure and as a mixture, at normothermic or hyperthermic conditions. The results showed that the mixture of MDMA and its metabolites was toxic to SH-SY5Y differentiated cells, an effect potentiated by hyperthermia and prevented by N-acetylcysteine. As a mixture, MDMA and its metabolites presented a different toxicity profile, compared to each compound alone, even at equimolar concentrations. Caspase 3 activation, increased reactive oxygen species production, and intracellular Ca(2+) raises were implicated in the toxic effect. The mixture increased intracellular glutathione levels by increasing its de novo synthesis. In conclusion, this study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at low micromolar concentrations, which represents a more realistic approach of the in vivo scenario, elicited toxicity to human SH-SY5Y differentiated cells, thus constituting a new insight into the context of MDMA-related neurotoxicity.

  5. Hair testing to assess both known and unknown use of drugs amongst ecstasy users in the electronic dance music scene.

    Palamar, Joseph J; Salomone, Alberto; Gerace, Enrico; Di Corcia, Daniele; Vincenti, Marco; Cleland, Charles M


    Data on both known and unknown drug use in the electronic dance music (EDM) scene is important to inform prevention and harm reduction. While surveys are the most common method of querying drug use, additional biological data can help validate use and detect unknown/unintentional use of drugs such as new psychoactive substances (NPS). We sought to determine the extent of both known and unknown use of various substances in this high-risk scene. We hair-tested 90 self-reported past-year ecstasy/MDMA/Molly users attending EDM parties in New York City during the summer of 2016 using UHPLC-MS/MS. Results were compared to self-reported past-year use. Three quarters (74.4%) tested positive for MDMA, a third (33.3%) tested positive for an NPS, and 27.8% tested positive specifically for one or more synthetic cathinones (e.g., butylone, ethylone, pentylone, methylone, alpha-PVP). Half (51.1%) of participants tested positive for a drug not self-reported, with most testing positive for synthetic cathinones (72.0%), methamphetamine (69.0%), other NPS stimulants (e.g., 4-FA, 5/6-APB; 66.7%), or new dissociatives (e.g., methoxetamine, diphenidine; 60.0%). Attending parties every other week or more often, reporting higher-frequency ecstasy pill use, having tested one's ecstasy, and having found out one's ecstasy was adulterated, were risk factors for testing positive for synthetic cathinones and NPS in general. Hair testing appears to be a valuable addition to drug epidemiology studies. Many EDM party attendees-even those who test their ecstasy-are unknowingly using NPS and/or other drugs. Prevention information and harm reduction may help reduce unknown/unintentional use. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Neurotoxic effects of ecstasy on the thalamus

    de Win, Maartje M. L.; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Silvia D.; Ramsey, Nick F.; den Heeten, Gerard J.; van den Brink, Wim


    Background Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. Aims To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, coc

  7. Profiles of urine samples taken from Ecstasy users at Rave parties: analysis by immunoassays, HPLC, and GC-MS.

    Zhao, H; Brenneisen, R; Scholer, A; McNally, A J; ElSohly, M A; Murphy, T P; Salamone, S J


    The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is increasing throughout the world. They have become popular drugs, especially at all-night techno dance parties (Raves), and their detection is becoming an important issue. Presently, there are no MDMA- or MDA-specific immunoassays on the market, and detection of the designer amphetamines is dependent upon the use of commercially available amphetamine assays. The success of this approach has been difficult to assess because of the general unavailability of significant numbers of samples from known drug users. The objectives of the present study are to characterize the drug content of urine samples from admitted Ecstasy users by chromatographic methods and to assess the ability of the available amphetamine/methamphetamine immunoassays to detect methylenedioxyamphetamines. We found that, when analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD), 64% of 70 urine samples (by gas chromatography-mass spectrometry [GC-MS]: 88% of 64 urine samples) obtained from Rave attendees contained MDMA and/or 3,4-methylenedioxyamphetamine (MDA) alone or in combination with amphetamine, methamphetamine, or other designer amphetamines such as 3,4-methylenedioxyethylamphetamine (MDEA). This suggests that the majority of the Ravers are multidrug users. At the manufacturer's suggested cutoffs, the Abbott TDx Amphetamine/Methamphetamine II and the new Roche HS Amphetamine/MDMA assays demonstrated greater detection sensitivity for MDMA than the other amphetamine immunoassays tested (Abuscreen OnLine Hitachi AMPS, Abuscreen OnLine Integra AMPS, Abuscreen OnLine Integra AMPSX, CEDIA AMPS, and EMIT II AMPS). There is 100% agreement between each of the two immunoassays with the reference chromatographic methods, HPLC-DAD and GC-MS, for the detection of methylenedioxyamphetamines.

  8. Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.

    Chuang-Hsin Chiu

    Full Text Available 3,4-Methylenedioxymethamphetamine (MDMA, also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI. Rats were injected subcutaneously six times with MDMA (5 mg/kg or saline once daily. Eight days after the last injection, manganese ions (Mn2+ were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB, and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.

  9. Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism.

    Rozas, C; Loyola, S; Ugarte, G; Zeise, M L; Reyes-Parada, M; Pancetti, F; Rojas, P; Morales, B


    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3-CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT₂ serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.

  10. [The cognitive effects of ecstasy].

    Pázmány, Péter; Petschner, Péter; Ádori, Csaba; Kirilly, Eszter; Andó, Dénes Rómeó; Balogh, Brigitta; Gyöngyösi, Norbert; Bagdy, György


    The recreational drug ecstasy is widely used among dance clubbers for its acute euphoric and entactogenic effects. Ecstasy exerts its acute effects by increasing the extracellular concentration of monoamines in the brain by reversing the functions of reuptake mechanisms. These elevations in extracellular monoamine concentrations result in wake promoting effects, body hyperthermia and reductions in local cerebral blood flow. However, on the long-run, ecstasy reduces serotonin concentration and density of serotonergic markers in several brain areas. Functional deficits, like sleep disturbances, anxiogenic- and aggressive behavioral responses and mood disorders also may occur. However, one of the most prominent adverse effects is related to the cognitive functions. Following ecstasy use attenuated retro- and prospective memory and defective higher order cognitive functions can be observed, especially in heavy users. Several studies indicated the involvement of the endocannabinoid system, the sleep regulating centers and the hypothalamic-pituitary-adrenal axis based on or parallel to serotonergic damage in these processes. Recent evidence, however, also showed that changes in one of the latter systems can influence the functions of each other. In this review we summarize the related literature, and propose a complex mechanism for the long-lasting cognitive deficits following heavy ecstasy use.

  11. Analysis of forensic samples of "Ecstasy" tablets seized in Novi Sad during the 2004 year

    Zgonjanin Dragana M.


    Full Text Available The paper presents results of the analysis of illicit synthetic drugs in the form of tablets distributed under the name "Ecstasy", seized by the police in the broader area of Novi Sad 2004. A huge number of tablets has been analyzed (n=121, of various colours and with impressed symbols from the total amount of 93 seizures, which totally amounted to 1458 tablets. Regarding the number of seizures ecstasy (3,4-methylendioxy-N-meth-yl-amphetamine - MDMA is dominant among all, and according to the quantity of seized tablets it is amphetamine (AP, while other amphetamine-type drugs (methamphetamine MA 3,4-methylendioxiamphetamine - MDA, 3,4-methylendioxi-N-ethyl-amphetamine MDEA have been found in rather small quantities and very rarely. Tablets mostly contain caffeine as an additive. In the analytical procedure, the samples of tablets were subjected to liquid-liquid extraction and afterwards analyzed on the GCD (GC-EI Hewlett-Packard instrument. The method is fast reliable and reproducible for the analysis of amphetamine, methamphetamine MDA, MDMA, MDEA, as well as various additives in the samples of seized tablets.

  12. Religious ecstasy in classical Sufism

    Göran Ogén


    Full Text Available The purpose of this essay is to shed some light on the phenomenon of religious ecstasy as met within Islamic mysticism and there particularly during its classical period. In this case, the expression "classical Sufism" refers to the period of Sufi history from about 850 A.D. until circa 1100 A.D. In the Sufi vocabulary there is even a rather differentiated terminology concerning these ecstatic experiences or states; whether different descriptions of one and the same experience are involved or whether the terms actually describe different experiences is a question that we must set aside for the present. There are, however, Sufis expressing the opinion that these different states of mind are based on one single experience in spite of the difference in terms. A generic term for these experiences or states is not to be found in the Sufi terminology however, so the problem of which of these phenomena must be present in order for ecstasy to be evidenced—or which of them would be sufficient— does not therefore arise for the Sufis. So instead of speaking of religious ecstasy in general, they either refer to the single specific terms in question or else use the plural of one of the words employed to designate one of the terms we include in "religious ecstasy". They thus speak of "ecstasies", mawagid from the singular form wagd—if one should at all attempt a translation of this plural. This plural is a genuine Sufi construction and does not otherwise seem to occur in the Arabic language, except as a later borrowing. Psalmody based on the Koranic vocabulary remains the main procedure for putting oneself in ecstasy. If we add 'and listening to psalmody', we then obtain a fairly satisfactory picture of the external conditions for the Sufis' ecstasy until the eleventh century, when various innovations begin to appear. As far as the darwiš-dance is concerned, it is not until the thirteenth century with Rumi that it becomes transformed from an expression

  13. Ecstasy analogues found in cacti.

    Bruhn, Jan G; El-Seedi, Hesham R; Stephanson, Nikolai; Beck, Olof; Shulgin, Alexander T


    Human interest in psychoactive phenethylamines is known from the use of mescaline-containing cacti and designer drugs such as Ecstasy. From the alkaloid composition of cacti we hypothesized that substances resembling Ecstasy might occur naturally. In this article we show that lophophine, homopiperonylamine and lobivine are new minor constituents of two cactus species, Lophophora williamsii (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of putatively psychoactive phenethylamines besides mescaline in these cacti. A search for further biosynthetic analogues may provide new insights into the structure-activity relationships of mescaline. An intriguing question is whether the new natural compounds can be called "designer drugs."

  14. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase.

    Anneken, John H; Cunningham, Jacobi I; Collins, Stuart A; Yamamoto, Bryan K; Gudelsky, Gary A


    3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus . Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure.

  15. Chemical profile of meta-chlorophenylpiperazine (m-CPP) in ecstasy tablets by easy ambient sonic-spray ionization, X-ray fluorescence, ion mobility mass spectrometry and NMR.

    Romão, Wanderson; Lalli, Priscila M; Franco, Marcos F; Sanvido, Gustavo; Schwab, Nicolas V; Lanaro, Rafael; Costa, José Luiz; Sabino, Bruno D; Bueno, Maria Izabel M S; de Sa, Gilberto F; Daroda, Romeu J; de Souza, Vanderlea; Eberlin, Marcos N


    Meta-chlorophenylpiperazine (m-CPP) is a new illicit drug that has been sold as ecstasy tablets. Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) and X-ray fluorescence spectrometry (XRF) are shown to provide relatively simple and selective screening tools to distinguish m-CPP tablets from tablets containing amphetamines (mainly 3,4-methylenedioxymethamphetamine (MDMA)). EASI-MS detects the active ingredients in their protonated forms: [m-CPP + H](+) of m/z 197, [MDMA + H](+) of m/z 194, and [2MDMA + HCl + H](+) of m/z 423 and other ions from excipients directly on the tablet surface, providing distinct chemical fingerprints. XRF identifies Cl, K, Ca, Fe, and Cu as inorganic ingredients present in the m-CPP tablets. In contrast, higher Cl concentrations and a more diverse set of elements (P, Cl, Ca, Fe, Cu, Zn, Pt, V, Hf, Ti, Pt, and Zr) were found in MDMA tablets. Principal component analysis applied to XRF data arranged samples in three groups: m-CPP tablets (four samples), MDMA tablets (twenty three samples), and tablets with no active ingredients (three samples). The EASI-MS and XRF techniques were also evaluated to quantify m-CPP in ecstasy tablets, with concentrations ranging from 4 to 40 mg of m-CPP per tablets. The m-CPP could only be differentiated from its isomers (o-CPP and for the three isomers p-CPP) by traveling wave ion mobility mass spectrometry and NMR measurements.

  16. Determination of amphetamine, methamphetamine, MDA and MDMA in human hair by GC-EI-MS after derivatization with perfluorooctanoyl chloride

    Johansen, Sys Stybe; Jornil, Jakob


    The aim of this study was to develop a quantitative gas chromatography mass spectrometry (GC-MS) method to determine the classical amphetamines and their methylenedioxylated derivatives in human hair. The procedure involved liquid-liquid extraction of hydrolysed hair spiked with deuterated internal....../mg and of quantification from 0.24 to 0.46 ng/mg, depending on compound. The method was applied on 40 authentic hair samples (segmented or pooled hair), of which 15 cases involved amphetamine and/or ecstasy. The hair concentrations ranged from LOD to 3.2 ng/mg of AM in 7 cases, to 0.4 ng/mg of MDA in 3 cases and to 5.9 ng....../mg of MDMA in 13 cases. MA was only detected once at trace level. The method, including the derivatization procedure, is simple and robust with a sensitivity that is satisfactory for measurement of amphetamines and ecstasy in hair from abusers....

  17. Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption.

    Llorente-Berzal, Alvaro; Puighermanal, Emma; Burokas, Aurelijus; Ozaita, Andrés; Maldonado, Rafael; Marco, Eva M; Viveros, Maria-Paz


    Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.

  18. The role of adenosine receptor agonist and antagonist on Hippocampal MDMA detrimental effects; a structural and behavioral study.

    Kermanian, Fatemeh; Mehdizadeh, Mehdi; Soleimani, Mansureh; Ebrahimzadeh Bideskan, Ali Reza; Asadi-Shekaari, Majid; Kheradmand, Hamed; Haghir, Hossein


    There is abundant evidence showing that repeated use of MDMA (3, 4-Methylenedioxymethamphetamine, ecstasy) has been associated with depression, anxiety and deficits in learning and memory, suggesting detrimental effects on hippocampus. Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. In the present study, we investigated the role of A2a adenosine receptors agonist (CGS) and antagonist (SCH) on the body temperature, learning deficits, and hippocampal cell death induced by MDMA administration. In this study, 63 adult, male, Sprague - Dawley rats were subjected to MDMA (10 and 20 mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03 mg/kg) injection. The animals were tested for spatial learning in the Morris water maze (MWM) task performance, accompanied by a recording of body temperature, electron microscopy and stereological study. Our results showed that MDMA treatment increased body temperature significantly, and impaired the ability of rats to locate the hidden platform(P mechanism of these interactions requires further studies.

  19. Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in the rat brain: an autoradiography study.

    Ciudad-Roberts, Andrés; Camarasa, Jorge; Pubill, David; Escubedo, Elena


    Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce a heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated male Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and sacrificed them the day after to perform [(125)I]Epibatidine binding autoradiograms on serial coronal slices. MDMA induced significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory, motor, auditory and retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 34% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The heteromeric nAChR up-regulation in certain areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term consumption of MDMA.

  20. Could MDMA Promote Stemness Characteristics in Mouse Embryonic Stem Cells via mGlu5 Metabotropic Glutamate Receptors?

    Rokhsareh Meamar


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

  1. {sup 15}N/{sup 14}N isotopic ratio and statistical analysis: an efficient way of linking seized Ecstasy tablets

    Palhol, Fabien; Lamoureux, Catherine; Chabrillat, Martine; Naulet, Norbert


    In this study, the {sup 15}N/{sup 14}N isotopic ratios of 106 samples of 3,4-methylenedioxymethamphetamine (MDMA) extracted from Ecstasy tablets are presented. These ratios, measured using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS), show a large discrimination between samples with a range of {delta}{sup 15}N values between -17 and +19%o, depending on the precursors and the method used in clandestine laboratories. Thus, {delta}{sup 15}N values can be used in a statistical analysis carried out in order to link Ecstasy tablets prepared with the same precursors and synthetic pathway. The similarity index obtained after principal component analysis and hierarchical cluster analysis appears to be an efficient way to group tablets seized in different places.

  2. The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

    Dias da Silva, Diana; Carmo, Helena; Silva, Elisabete


    The recreational and illicit use of amphetaminic designer compounds, specially 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such psychostimulating drugs are frequently present as complex mixtures in 'rave' pills, making concomitant polysubstance use a common trend. However, the understanding of possible combination effects with these substances is still scarce. The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line. Concentration-response curves for all single-mixture components were recorded by the MTT assay. Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action. By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations. Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects. Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels. A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity. In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.

  3. Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA and Its Phase I and II Metabolites in Humans.

    Andrea E Steuer

    Full Text Available 3,4-methylenedioxymethamphetamine (MDMA; ecstasy metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA, followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs, intermediate metabolizers (IMs, and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax and area under the plasma concentration-time curve from 0 to 24 h (AUC24 of R-MDMA (9% and 25%, respectively and S-MDMA (16% and 38%, respectively. Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism.

  4. Cosmic Ecstasy and Process Theology

    Blair Reynolds


    Full Text Available The notion that God and the world are mutually interdependent is generally taken to be unique to twentieth-century process theology. Largely, process thinkers have focused on classical theists, rather than the mystics. My thesis, however, is that, centuries before process came along, there were Western mystical concepts stressing that God needed the universe in order to become conscious and complete. In support of my thesis, I will provide a synopsis of the doctrines of God as found in mystics such as Boehme, Dionysius, Eckhart, and then show how Whitehead’s aesthetic provides a coherent philosophical psychology of ecstasy. Key words: aesthetic experience, causal efficacy, consequent nature of God, ecstasy, feeling, German Romanticism, primordial nature of God, reformed subjectivist principle, Nicht, unconscious experience.

  5. Cosmic Ecstasy and Process Theology

    Blair Reynolds


    Full Text Available The notion that God and the world are mutually interdependent is generally taken to be unique to twentieth-century process theology. Largely, process thinkers have focused on classical theists, rather than the mystics. My thesis, however, is that, centuries before process came along, there were Western mystical concepts stressing that God needed the universe in order to become conscious and complete. In support of my thesis, I will provide a synopsis of the doctrines of God as found in mystics such as Boehme, Dionysius, Eckhart, and then show how Whitehead’s aesthetic provides a coherent philosophical psychology of ecstasy. Key words: aesthetic experience, causal efficacy, consequent nature of God, ecstasy, feeling, German Romanticism, primordial nature of God, reformed subjectivist principle, Nicht, unconscious experience.

  6. On satisfaction, happiness and ecstasy.

    Deutsch, H


    In her 1927 'On satisfaction, happiness and ecstasy' Helene Deutsch took a respectful attitude toward religious phenomena. She was also talking about emotional states that Freud was apt not to want to write about because of his own scepticism concerning them. She even touched with understanding tolerance on the blissfulness of religious communion. She proceeded from the premise of a universal striving in each individual for psychological unity. She used two case histories to illustrate how both sexual satisfaction and sublimation could involve heightened phases of dejection. She accounted for the sense of ecstasy by the temporarily undisturbed unity between ego and non-ego. This translation should help counter-act the ahistoric tendency to look on early psychoanalysis only from the perspective of our own preoccupations. In her interest in the 'feeling of happiness' Helene Deutsch was anticipating later thinking which sought to include within psychoanalytic theory the integrative processes that constitute harmony.

  7. Designer Drug Confusion: A Focus on MDMA.

    Beck, Jerome; Morgan, Patricia A.


    Discusses the competing definitions and issues surrounding various designer drugs, primarily 3, 4-methylenedioxy-methamphetamine (MDMA). Offers a rationale for why interest in MDMA, which possesses both stimulant and psychedelic properties, will continue to grow despite the drug's recent illegality and increasing evidence of neurotoxicity.…

  8. Anxiogenic-like activity of 3,4-methylenedioxy-methamphetamine ("Ecstasy") in the social interaction test is accompanied by an increase of c-fos expression in mice amygdala.

    Navarro, José Francisco; Rivera, Alicia; Maldonado, Enrique; Cavas, María; de la Calle, Adelaida


    3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine popularly known as "Ecstasy." Animal studies examining acute effects of MDMA on anxiety are unclear because although an anxiolytic-like action of MDMA in different animal models of anxiety has been described, there is also substantial evidence supporting an anxiogenic-like effect of this drug. To date, several studies have examined c-fos expression following MDMA administration in rats. However, there is no information about the MDMA-induced c-fos expression in mice previously tested in an animal model of anxiety. In this study, male mice were injected with MDMA (1, 8 and 15 mg/kg ip) and assessed for changes on anxiety and for the expression of the immediate early gene c-fos in the amygdala (central, basolateral and basomedial). Anxiety was evaluated by the "social interaction test." Ten behavioral categories were recorded: body care, digging, nonsocial exploration, exploration from a distance, social investigation, threat, attack, avoidance/flee, defense/submission and immobility. As compared with the control group, mice treated with MDMA (all doses) showed a decrease in mean duration and total time spent in social investigation behaviors, whereas avoidance/flee behaviors were significantly increased after treatment with this compound (8 and 15 mg/kg). Likewise, a significant increase in c-fos expression was found in the basolateral (all doses) and central (15 mg/kg) amygdala after MDMA administration. Overall, these findings indicate that MDMA exhibits an anxiogenic-like profile in the social interaction test in mice, and that central and basolateral amygdala might be involved in these anxiogenic-like effects of the drug.

  9. Factors Associated with Teenage Ecstasy Use

    Mccrystal, Patrick; Percy, Andrew


    Aims: The aim of this article was to investigate the factors associated with ecstasy use in school-aged teenagers. Methods: This was a longitudinal study of adolescent drug use, which was undertaken in three towns in Northern Ireland. A questionnaire was administered annually to participants. In this article ecstasy use patterns amongst a cohort…

  10. "Êxtase": revisão farmacológica "Ecstasy": a pharmacological review

    Maristela Ferigolo


    Full Text Available Neste estudo fez-se uma revisão bibliográfica sobre a 3,4- metilenodioximetan-fetamina (MDMA, mais conhecida como "êxtase", uma droga em expansão de abuso entre os jovens. Descreve-se o histórico, desde sua síntese até seu uso inicial como auxiliar em psicoterapia e, mais recentemente, como droga de abuso. Apresenta-se o perfil de uso em outros países, tentando prever o possível padrão de uso no Brasil, onde já se iniciou o abuso. O detalhamento sobre a farmacocinética da MDMA visa a justificar as conseqüências sobre a atividade farmacológica e toxicológica. Resumem-se as manifestações clínicas de toxicidade a curto e a médio prazo, descrevendo-se os efeitos na intoxicação grave com o "êxtase". São apresentados os estudos dos mecanismos de ação no sentido de justificar seus efeitos tóxicos psíquicos e físicos, detalhar os mecanismos pelos quais a droga é auto-administrada e as possibilidades terapêuticas para reverter os efeitos.A literature review on 3,4 methylenedioxymethanphetaneine (MDMA,. known as ecstasy, a drug with increased use among youngsters is presented. The history from its synthesis, up to its use as an adjunct to psychotherapy and, more recently, as a drug of abuse, is described. The possible pattern of abuse in several countries is reviewed with the objective of predicting what might happen in Brazil, where some reports of abuse have already appeared. The pharmacokinetics of MDMA is also reviewed to explain the consequences for pharmacological activity, toxicology and adverse effects. The clinical outcome of both short and middle-term intoxication is summarized and the clinical symptoms of severe intoxication with ecstasy, are described. The studies undertaken on its mechanism of action are detailed to explain its toxic psychiatric and physical side effects, to explain the mechanism of self-administration of the drug and to propose a therapeutic possibility of treating intoxication.

  11. Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.

    Lott, S; Musshoff, F; Madea, B


    There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected by police during road side testing for GHB. The samples subject to this study have already been found to be positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDEA). Analysis has been performed by LC/MS/MS in the multiple reaction monitoring (MRM) mode. Due to its polarity, chromatographic separation of GHB was achieved by a HILIC column. To differentiate endogenous and exogenous levels of GHB, a cut-off concentration of 4μg/ml was applied. Of the 196 samples, two have been found to be positive for GHB. Of these samples, one sample was also positive for amphetamine and one for MDMA. Whilst other amphetamine derivates were not detected in these samples, both samples were found to be positive for cannabinoids. These results suggest that co-consumption of GHB with amphetamine or ecstasy is relatively low (1%) for the collective of this study.

  12. The effects of the 3,4-methylenedioxymethamphetamine (Ecstasy) in some cerebral areas: role of the oxidative stress.

    Franzese, Sergio; Capasso, Anna


    The purpose of the present review is to examine the effect of the acute administration (20 mg/ Kg, i.p.) of the 3,4 methylenedioxymethamphetamine (MDMA) in different cerebral areas of rats to better understand the mechanism underlying the toxicity induced by cellular oxidative stress. For this purpose the biochemical parameters of the antioxidant non-enzymatic cellular defense system have been studied (the reduced Glutathione (GSH), the Glutathione Disulfide (GSSG), the Ascorbic Acid (AA) and malondialdehyde (MDA) which indicates perioxidative damage) in the hippocampus, striate, frontal cortex both in treated animals and in control groups to realize a qualitative-quantitative evaluation of the possible alterations of the neuronal redox state induced by the administration of Ecstasy. The administration of MDMA induced the following variations of the antioxidant non enzymatic defense system: 1. the levels of the AA in the treated animals compared with the control group were increased in the striate, hippocampus and in the frontal cortex both at 3h and 6h. 2. In the striate, also MDA was significantly increased both after 3 h and 6 h, while in the hippocampus and in the frontal cortex the MDA was significantly increased after 6 h. 3. An increase of GSH was also observed after 3 h and 6 h in the hippocampus and in the striate while no significative variation were observed in the frontal cortex of the treated rats. 4. An increase of GSSG was significative in the hippocampus and striate at 3h, while at 6h it was significative only in the striate. In conclusion the results of our study seem to confirm the role of the oxidative stress in the mechanism of neuronal toxicity induced by Ecstasy and leads us to hypothesize a possible role of the antioxidant substances in the therapeutic treatment of the intoxicants by MDMA.

  13. Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

    Buchert, Ralph; Wilke, Florian; Nebeling, Bruno; Clausen, Malte [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Thomasius, Rainer; Petersen, Kay; Obrocki, Jost; Wartberg, Lutz; Zapletalova, Pavlina [University Medical Center Hamburg-Eppendorf, Departments of Psychiatry and Psychotherapy, Hamburg (Germany)


    Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [{sup 11}C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)


    expressing mystical ecstasy in angelic and human figures. It is introduced with a brief ..... The ancient Greek attitude of praying — upright, arms lifted and extended. — opened and .... In: Allegory and the migration of symbols. (London: Thames ...

  15. Ecstasy from a physiological point of view

    Kaj Björkqvist


    The biological study of man is one of today's most rapidly advancing sciences. There is no reason for not utilizing these methodologies of research and the knowledge already gained when studying ecstasy and other similar religious phenomena. Drugs have been used in all parts of the world as an ecstasy technique. Since mental states and physiological correlates always accompany each other, it is obvious that the human mind can be affected by external means, for instance by drugs. But the oppos...

  16. Ecstasy from a physiological point of view

    Kaj Björkqvist


    Full Text Available The biological study of man is one of today's most rapidly advancing sciences. There is no reason for not utilizing these methodologies of research and the knowledge already gained when studying ecstasy and other similar religious phenomena. Drugs have been used in all parts of the world as an ecstasy technique. Since mental states and physiological correlates always accompany each other, it is obvious that the human mind can be affected by external means, for instance by drugs. But the opposite is also true; mental changes affect the body, as they do in the case of psychosomatic diseases. Ecstasy is often described as an extremely joyful experience; this pleasure must necessarily also have a physiological basis. It is of course too early to say anything for certain, but the discovery of pleasure centres in the brain might offer an explanation. It is not far-fetched to suggest that when a person experiences euphoric ecstasy, it might, in some way or other, be connected with a cerebral pleasure center. Can it be, for example, that religious ecstasy is attained only by some mechanism triggering off changes in the balance of the transmitter substances? Or is it reached only via a change in the hormonal balance, or only by a slowing down of the brain waves, or is a pleasure centre activated? When a person is using an ecstasy technique, he usually does so within a religious tradition. When he reaches an experience, a traditional interpretation of it already exists.

  17. Long-term neuropsychological effects of ecstasy in middle-aged ecstasy/polydrug users

    T. Schilt; M.W.J. Koeter; J.P. Smal; M.N. Gouwetor; W. van den Brink; B. Schmand


    Rationale Studies reporting ecstasy-induced serotonin-toxicity and (neuro)psychological dysfunctions have been conducted in young adults. Little is known about ecstasy effects later in life, when serotonin levels and cognition decrease as a consequence of normal ageing. Objective This study aimed to

  18. Ecstasy (MDMA and its Relationship with Self-Report Depression, Anxiety and Schizotypy

    Lisa Wood


    Full Text Available Objetivos: la relación entre el consumo de éxtasis y síntomas afectivos es aún objeto de debate. Nuestro objetivo es examinar la relación entre el consumo de éxtasis y la depresión, ansiedad y esquizotipia autoinformadas. Diseño: los datos fueron recogidos a través de medidas de autoinforme estructuradas. Participantes: los participantes se dividieron en tres grupos: grupo control que no consumía éxtasis, grupo de consumidores de éxtasis en grado bajo (<50 veces, y grupo de consumidores de éxtasis grado alto (< 50 veces. Instrumentos: se registró la cantidad y patrón de consumo de éxtasis, y se utilizó el Inventario de Depresión de Beck (BDI para evaluar depresión, el Inventario de Ansiedad de Beck (BAI para evaluar ansiedad, y el Cuestionario de Personalidad Esquizotípica (SPQ para evaluar rasgos esquizotípicos. Resultados: el consumo de éxtasis está relacionado con las puntuaciones de rasgo de depresión, ansiedad y esquizotipia. No se ha encontrado relación entre las medidas de autoinforme y el grado de consumo de éxtasis. Conclusiones: el consumo de éxtasis se relaciona con las puntuaciones en depresión y ansiedad autoinformada, replicado la evidencia ya existente en la literatura. Más aún, los consumidores de éxtasis presentaron mayores puntuaciones en rasgos esquizotípicos, algo que no se había documentado en ninguna investigación anterior.

  19. Predicting Ecstasy Use among Young People at Risk: A Prospective Study of Initially Ecstasy-Naive Subjects

    Vervaeke, Hylke K.E.; Benschop, Annemieke; Van Den Brink, Wim; Korf, Dirk J.


    Our aim is to identify predictors of first-time ecstasy use in a prospective study among young people at risk. As part of the multidisciplinary Netherlands XTC Toxicity Study (NeXT), we monitored 188 subjects aged up to 18 years who were ecstasy-naive at baseline but seemed likely to start taking ecstasy in the near future. After an 11- to…

  20. Predicting ecstasy use among young people at risk: a prospective study of initially ecstasy-naive subjects

    H.K.E. Vervaeke; A. Benschop; W. van den Brink; D.J. Korf


    Our aim is to identify predictors of first-time ecstasy use in a prospective study among young people at risk. As part of the multidisciplinary Netherlands XTC Toxicity Study (NeXT), we monitored 188 subjects aged ≥ 18 who were ecstasy-naive at baseline but seemed likely to start taking ecstasy in t

  1. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Mayado Andrea


    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  2. Ecstasy exposure & gender: examining components of verbal memory functioning.

    Jenessa S Price

    Full Text Available OBJECTIVE: Studies have demonstrated verbal memory deficits associated with past year ecstasy use, although specific underlying components of these deficits are less understood. Further, prior research suggests potential gender differences in ecstasy-induced serotonergic changes. Therefore, the current study investigated whether gender moderated the relationship between ecstasy exposure and components of verbal memory after controlling for polydrug use and confounding variables. METHOD: Data were collected from 65 polydrug users with a wide range of ecstasy exposure (ages 18-35; 48 ecstasy and 17 marijuana users; 0-2310 ecstasy tablets. Participants completed a verbal learning and memory task, psychological questionnaires, and a drug use interview. RESULTS: Increased past year ecstasy exposure predicted poorer short and long delayed free and cued recalls, retention, and recall discrimination. Male ecstasy users were more susceptible to dose-dependent deficits in retention than female users. CONCLUSION: Past year ecstasy consumption was associated with verbal memory retrieval, retention, and discrimination deficits in a dose-dependent manner in a sample of healthy young adult polydrug users. Male ecstasy users were at particular risk for deficits in retention following a long delay. Gender difference may be reflective of different patterns of polydrug use as well as increased hippocampal sensitivity. Future research examining neuronal correlates of verbal memory deficits in ecstasy users are needed.

  3. Effects of Stress and MDMA on Hippocampal Gene Expression

    Georg F. Weber


    Full Text Available MDMA (3,4-methylenedioxymethamphetamine is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD. On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT nerve terminals that have been viewed as indicative of 5-HT neurotoxicity. Exposure to chronic stress has been shown to augment MDMA-induced 5-HT neurotoxicity. Here, we examine the transcriptional responses in the hippocampus to MDMA treatment of control rats and rats exposed to chronic stress. MDMA altered the expression of genes that regulate unfolded protein binding, protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling. In stressed rats, the gene expression profile in response to MDMA was altered to affect sensory processing and responses to tissue damage in nerve sheaths. Subsequent treatment with MDMA also markedly altered the genetic responses to stress such that the stress-induced downregulation of genes related to the circadian rhythm was reversed. The data support the view that MDMA-induced transcriptional responses accompany the persistent effects of this drug on neuronal structure/function. In addition, MDMA treatment alters the stress-induced transcriptional signature.

  4. Crime and Violence among MDMA Users in the United States

    Michael G. Vaughn


    Full Text Available The question of whether MDMA use is associated with increased crime and violence has not been adequately explored especially in nationally representative samples. This study used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC to assess the association between MDMA use and violent and non-violent antisocial behavior while controlling for sociodemographic variables, lifetime psychiatric, alcohol and drug use disorders, and family history of antisocial behavior. MDMA users, both male and female, were involved in a number of crimes in acts of violence including drunk driving, shoplifting, theft, intimate partner violence, and fighting. Notably, female MDMA users were more antisocial than male non-MDMA users. Although adjusting the results for numerous confounds attenuated the relationships, MDMA users were still at significantly greater odds of engaging in violent and nonviolent crime than non-MDMA users. Although MDMA has been considered a facilitator of empathy and closeness, the current study suggests a dark side as MDMA is associated with a broad array of crimes and transgressions. Additional tests of the MDMA-crime link are needed to properly inform policy.

  5. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors.

    Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M Paula M; Borges, Fernanda


    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-beta-methyl-beta-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

  6. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

    Milhazes, Nuno [CEQOFFUP, Faculdade de Farmacia, Universidade do Porto (Portugal); Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal); Instituto Superior de Ciencias da Saude-Norte, Gandra, Paredes (Portugal); Martins, Pedro [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Uriarte, Eugenio [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Garrido, Jorge [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Engenharia Quimica, ISEP, Instituto Politecnico do Porto (Portugal); Calheiros, Rita [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Marques, M. Paula M. [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Bioquimica, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra (Portugal); Borges, Fernanda [Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal) and Unidade I and D ' Quimica-Fisica Molecular' (Portugal)]. E-mail:


    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-{beta}-methyl-{beta}-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

  7. Illicit use of LSD or psilocybin, but not MDMA or nonpsychedelic drugs, is associated with mystical experiences in a dose-dependent manner.

    Lyvers, Michael; Meester, Molly


    Psychedelic drugs have long been known to be capable of inducing mystical or transcendental experiences. However, given the common "recreational" nature of much present-day psychedelic use, with typical doses tending to be lower than those commonly taken in the 1960s, the extent to which illicit use of psychedelics today is associated with mystical experiences is not known. Furthermore the mild psychedelic MDMA ("Ecstasy") is more popular today than "full" psychedelics such as LSD or psilocybin, and the contribution of illicit MDMA use to mystical experiences is not known. The present study recruited 337 adults from the website and newsletter of the Multidisciplinary Association for Psychedelic Studies (MAPS), most of whom reported use of a variety of drugs both licit and illicit including psychedelics. Although only a quarter of the sample reported "spiritual" motives for using psychedelics, use of LSD and psilocybin was significantly positively related to scores on two well-known indices of mystical experiences in a dose-related manner, whereas use of MDMA, cannabis, cocaine, opiates and alcohol was not. Results suggest that even in today's context of "recreational" drug use, psychedelics such as LSD and psilocybin, when taken at higher doses, continue to induce mystical experiences in many users.

  8. Neural mechanisms underlying ecstasy-related attentional bias.

    Roberts, Gloria M P; Garavan, Hugh


    Conditioned responses to cues associated with drug taking play a pivotal role in a number of theories of drug addiction. This study examined whether attentional biases towards drug-related cues exist in recreational drug users who predominantly used ecstasy (3,4-methylenedioxymethamphetamine). Experiment 1 compared 30 ecstasy users, 25 cannabis users, and 30 controls in an attentional distraction task in which neutral, evocative, and ecstasy-related pictures were presented within a coloured border, requiring participants to respond as quickly as possible to the border colour. Experiment 2 employed functional magnetic resonance imaging (fMRI) and the attentional distraction task and tested 20 ecstasy users and 20 controls. Experiment 1 revealed significant response speed interference by the ecstasy-related pictures in the ecstasy users only. Experiment 2 revealed increased prefrontal and occipital activity in ecstasy users in all conditions. Activations in response to the ecstasy stimuli in these regions showed an apparent antagonism whereby ecstasy users, relative to controls, showed increased occipital but decreased right prefrontal activation. These results are interpreted to reflect increased visual processing of, and decreased prefrontal control over, the irrelevant but salient ecstasy-related stimuli. These results suggest that right inferior frontal cortex may play an important role in controlling drug-related attentional biases and may thus play an important role in mediating control over drug usage.

  9. MDMA reinstates cocaine-seeking behaviour in mice.

    Trigo, José Manuel; Orejarena, Maria Juliana; Maldonado, Rafael; Robledo, Patricia


    MDMA effects are mediated by monoaminergic systems, which seem to play a central role in cocaine craving and relapse. CD1 mice trained to self-administer cocaine (1 mg/kg/infusion) underwent an extinction procedure in which the cues contingent with drug self-administration remained present. Mice achieving extinction were injected with MDMA (10 mg/kg), d-amphetamine (1 and 2 mg/kg) or saline and tested for reinstatement. Acute MDMA, but not d-amphetamine or saline reinstated cocaine-seeking behaviour in mice in which cocaine self-administration and contingent cues were previously extinguished. Acute MDMA can reinstate cocaine-seeking behaviour in mice.

  10. Analysis of ecstasy in oral fluid by ion mobility spectrometry and infrared spectroscopy after liquid-liquid extraction.

    Armenta, Sergio; Garrigues, Salvador; de la Guardia, Miguel; Brassier, Judit; Alcalà, Manel; Blanco, Marcelo


    We developed and evaluated two different strategies for determining abuse drugs based on (i) the analysis of saliva by ion mobility spectrometry (IMS) after thermal desorption and (ii) the joint use of IMS and infrared (IR) spectroscopy after liquid-liquid microextraction (LLME) to enable the sensitivity-enhanced detection and double confirmation of ecstasy (MDMA) abuse. Both strategies proved effective for the intended purpose. Analysing saliva by IMS after thermal desorption, which provides a limit of detection (LOD) of 160μgL(-1), requires adding 0.2M acetic acid to the sample and using the truncated negative second derivative of the ion mobility spectrum. The joint use of IMS and IR spectroscopy after LLME provides an LOD of 11μgL(-1) with the former technique and 800μgL(-1) with the latter, in addition to a limit of confirmation (LOC) of 1.5mgL(-1). Using IMS after thermal desorption simplifies the operational procedure, and using it jointly with IR spectroscopy after LLME allows double confirmation of MDMA abuse with two techniques based on different principles (viz., IMS drift times and IR spectra). Also, it affords on-site analyses, albeit at a lower throughput.

  11. Mixtures of 3,4-methylenedioxymethamphetamine (ecstasy) and its major human metabolites act additively to induce significant toxicity to liver cells when combined at low, non-cytotoxic concentrations.

    da Silva, Diana Dias; Silva, Elisabete; Carvalho, Félix; Carmo, Helena


    Hepatic injury after 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) intoxications is highly unpredictable and does not seem to correlate with either dosage or frequency of use. The mechanisms involved include the drug metabolic bioactivation and the hyperthermic state of the liver triggered by its thermogenic action and exacerbated by the environmental circumstances of abuse at hot and crowded venues. We became interested in understanding the interaction between ecstasy and its metabolites generated in vivo as users are always exposed to mixtures of parent drug and metabolites. With this purpose, Hep G2 cells were incubated with MDMA and its main human metabolites methylenedioxyamphetamine (MDA), α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA), individually and in mixture (drugs combined in proportion to their individual EC01 ), at normal (37 °C) and hyperthermic (40.5 °C) conditions. After 48 h, viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Extensive concentration-response analysis was performed with single drugs and the parameters of the individual non-linear logit fits were used to predict joint effects using the well-founded models of concentration addition (CA) and independent action (IA). Experimental testing revealed that mixture effects on cell viability conformed to CA, for both temperature settings. Additionally, substantial combination effects were attained even when each substance was present at concentrations that individually produced unnoticeable effects. Hyperthermic incubations dramatically increased the toxicity of the tested drug and metabolites, both individually and combined. These outcomes suggest that MDMA metabolism has hazard implications to liver cells even when metabolites are found in low concentrations, as they contribute additively to the overall toxic effect of MDMA.

  12. Young adults' trajectories of Ecstasy use: a population based study.

    Smirnov, Andrew; Najman, Jake M; Hayatbakhsh, Reza; Plotnikova, Maria; Wells, Helene; Legosz, Margot; Kemp, Robert


    Young adults' Ecstasy use trajectories have important implications for individual and population-level consequences of Ecstasy use, but little relevant research has been conducted. This study prospectively examines Ecstasy trajectories in a population-based sample. Data are from the Natural History Study of Drug Use, a retrospective/prospective cohort study conducted in Australia. Population screening identified a probability sample of Ecstasy users aged 19-23 years. Complete data for 30 months of follow-up, comprising 4 time intervals, were available for 297 participants (88.4% of sample). Trajectories were derived using cluster analysis based on recent Ecstasy use at each interval. Trajectory predictors were examined using a generalized ordered logit model and included Ecstasy dependence (World Mental Health Composite International Diagnostic Instrument), psychological distress (Hospital Anxiety Depression Scale), aggression (Young Adult Self Report) and contextual factors (e.g. attendance at electronic/dance music events). Three Ecstasy trajectories were identified (low, intermediate and high use). At its peak, the high-use trajectory involved 1-2 days Ecstasy use per week. Decreasing frequency of use was observed for intermediate and high-use trajectories from 12 months, independently of market factors. Intermediate and high-use trajectory membership was predicted by past Ecstasy consumption (>70 pills) and attendance at electronic/dance music events. High-use trajectory members were unlikely to have used Ecstasy for more than 3 years and tended to report consistently positive subjective effects at baseline. Given the social context and temporal course of Ecstasy use, Ecstasy trajectories might be better understood in terms of instrumental rather than addictive drug use patterns.

  13. Development of a Multiple-Stage Differential Mobility Analyzer (MDMA)

    Chen, Da-Ren [ORNL; Cheng, Mengdawn [ORNL


    A new DMA column has been designed with the capability of simultaneously extracting monodisperse particles of different sizes in multiple stages. We call this design a multistage DMA, or MDMA. A prototype MDMA has been constructed and experimentally evaluated in this study. The new column enables the fast measurement of particles in a wide size range, while preserving the powerful particle classification function of a DMA. The prototype MDMA has three sampling stages, capable of classifying monodisperse particles of three different sizes simultaneously. The scanning voltage operation of a DMA can be applied to this new column. Each stage of MDMA column covers a fraction of the entire particle size range to be measured. The covered size fractions of two adjacent stages of the MDMA are designed somewhat overlapped. The arrangement leads to the reduction of scanning voltage range and thus the cycling time of the measurement. The modular sampling stage design of the MDMA allows the flexible configuration of desired particle classification lengths and variable number of stages in the MDMA. The design of our MDMA also permits operation at high sheath flow, enabling high-resolution particle size measurement and/or reduction of the lower sizing limit. Using the tandem DMA technique, the performance of the MDMA, i.e., sizing accuracy, resolution, and transmission efficiency, was evaluated at different ratios of aerosol and sheath flowrates. Two aerosol sampling schemes were investigated. One was to extract aerosol flows at an evenly partitioned flowrate at each stage, and the other was to extract aerosol at a rate the same as the polydisperse aerosol flowrate at each stage. We detail the prototype design of the MDMA and the evaluation result on the transfer functions of the MDMA at different particle sizes and operational conditions.

  14. MDMA Impairs Response to Water Intake in Healthy Volunteers

    Matthew J. Baggott


    Full Text Available Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH. In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk.

  15. Campuses and the Club Drug Ecstasy. Infofacts/Resources

    Powell, Amy


    Although alcohol is the drug that college students use most frequently and in greatest quantity, the designer drug ecstasy has generated both curiosity and concern in recent years. This Fact Sheet offers an overview of ecstasy, possible effects of its use, and implications for institutions of higher education. Although the number of students…

  16. Cognitive disorders after sporadic ecstasy use? A case report

    Ruis, Carla; Postma, Albert; Bouvy, Willem; van der Ham, Ineke


    Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is

  17. Cognitive disorders after sporadic ecstasy use? A case report.

    Ruis, Carla; Postma, Albert; Bouvy, Willem; van der Ham, Ineke


    Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is a 39-year-old man who used an ecstasy tablet in 2005. This resulted in severe confusion for a few days. The confusion was followed by persistent memory complaints and difficulties orientating in new surroundings. An extensive neuropsychological examination 7 years after the ecstasy use revealed a severe memory disorder. Furthermore, his performance on a virtual reality test of navigation showed serious problems navigating in new surroundings. In comparison with matched control subjects (Bayesian approach for single case studies) his scores were significantly impaired on several subtasks of the navigation test. On a magnetic resonance imaging (MRI) scan of the brain bilateral hippocampal atrophy and sclerosis were visible, comparable to previous MRI studies describing hippocampal damage following ecstasy ingestion. This case report describes persistent memory and navigation disorders after sporadic ecstasy use, supported by structural brain abnormalities seen on the MRI scan. These findings revive the debate on whether sporadic ecstasy use can cause persistent cognitive deficits.

  18. Intimate insight: MDMA changes how people talk about significant others.

    Baggott, Matthew J; Kirkpatrick, Matthew G; Bedi, Gillinder; de Wit, Harriet


    ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions. Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker's Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers. Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions. These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction. © The Author(s) 2015.

  19. Moral panic in Icelandic society: Arrival of ecstasy to Iceland

    Jón Orri Jónasson


    Full Text Available The use of illegal drugs has often been shown to ignite fear and insecurity in society. When a new drug appears the media typically reports on this drug and the risk it poses. Soon after ecstasy appeared in Iceland in the 1990s its use created a major public uproar and insecurity in Icelandic society. In the article the theory of moral panic will be used to examine if the arrival of ecstasy to Iceland ignited a moral panic. Media reports on ecstasy, public reactions, interest groups and government institutions will be analysed. Discourse analysis is employed on newspaper reporting on ecstasy between 1985 and 1997 to detect signs of moral panic. The main conclusion is that evidence suggests that a moral panic existed in Iceland as described in well-known theories on the subject.

  20. -Regular Modules

    Areej M. Abduldaim


    Full Text Available We introduced and studied -regular modules as a generalization of -regular rings to modules as well as regular modules (in the sense of Fieldhouse. An -module is called -regular if for each and , there exist and a positive integer such that . The notion of -pure submodules was introduced to generalize pure submodules and proved that an -module is -regular if and only if every submodule of is -pure iff   is a -regular -module for each maximal ideal of . Many characterizations and properties of -regular modules were given. An -module is -regular iff is a -regular ring for each iff is a -regular ring for finitely generated module . If is a -regular module, then .

  1. Calpain- and caspase-mediated alphaII-spectrin and tau proteolysis in rat cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure.

    Warren, Matthew W; Zheng, Wenrong; Kobeissy, Firas H; Cheng Liu, Ming; Hayes, Ronald L; Gold, Mark S; Larner, Stephen F; Wang, Kevin K W


    Abuse of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) and methamphetamine (Meth or Speed) is a growing international problem with an estimated 250 million users of psychoactive drugs worldwide. It is important to demonstrate and understand the mechanism of neurotoxicity so potential prevention and treatment therapies can be designed. In this study rat primary cerebrocortical neuron cultures were challenged with MDMA and Meth (1 or 2 mM) for 24 and 48 h and compared to the excitotoxin N-methyl-D-aspartate (NMDA). The neurotoxicity of these drugs, as assessed by microscopy, lactate dehydrogenase release and immunoblot, was shown to be both dose- and time-dependent. Immunoblot analysis using biomarkers of cell death showed significant proteolysis of both alphaII-spectrin and tau proteins. Breakdown products of alphaII-spectrin (SBDPs) of 150, 145, and 120 kDa and tau breakdown products (TBDPs) of 45, 32, 26, and 14 kDa were observed. The use of the protease inhibitors calpain inhibitor SJA6017 and caspase inhibitors z-VAD-fmk and Z-D-DCB, attenuated drug-induced alphaII-spectrin and tau proteolysis. The calpain inhibitor reduced the calpain-induced breakdown products SBDP145 and TBDP14, but there was an offset increase in the caspase-mediated breakdown products SBDP120 and TBDP45. The caspase inhibitors, on the other hand, decreased SBDP120 and TBDP45. These data suggest that both MDMA and Meth trigger concerted proteolytic attacks of the structural proteins by both calpain and caspase family of proteases. The ability of the protease inhibitors to reduce the damage caused by these drugs suggests that the treatment arsenal could include similar drugs as possible tools to combat the drug-induced neurotoxicity in vivo.

  2. The Hepatoprotective Effects of Corn Silk against Dose-induced Injury of Ecstasy (MDMA Using Isolated Rat Liver Perfusion System

    Mohammad Karami


    Full Text Available Background: Corn silk (CS is widely used in Iranian traditional medicine. The aim of this study was to investigate hepatoprotective activity of CS by Isolated Rat Liver Perfusion System (IRLP. Methods: Hydro-alcoholic extract of corn silk (10, 20, 40, and 100 mg kg-1 was evaluated for its hepatoprotective activity by IRLP. Phenol and flavonoid contents of the extract were determined as gallic acid and quercetin equivalents from a calibration curve, respectively. IRLP system is ideal for studying biochemical alterations of chemicals with minimum neuro-hormonal effects. In this study, the liver was perfused with Kerbs-Henseleit buffer, containing different concentration of hydro-alcoholic extract of corn silk (10, 20, 40, 50,100mg/kg, added to the buffer, and perfused for 2 hours. During the perfusion, many factors, including amino-transferees activities and the level of GSH, were assessed as indicators of liver viability. Consequently, sections of liver tissues were examined for any histopathological changes. Results: Histopathological changes in liver tissues were related to hydro-alcoholic extract of corn silk concentrations in a dose-dependent manner. Also, 50 and 100mg/kg doses caused significant (P<0.05 histopathological changes. Level of GSH in samples perfused with hydro-alcoholic extract increased compared to the control group. Conclusion: Hepatoprotective effect of CS is due to decreased lipid peroxidation, although other mechanisms might also be involved.

  3. Nephroprotective effects of Feijoa Sellowiana leaves extract on renal injury induced by acute dose of ecstasy (MDMA in mice

    Mohammad Karami


    : Both extracts at 40 mg/kg resulted in a significant reversal in the raised serum creatinine levels (P 0.05. A decrease in urea/ creatinine ratio was observed following aqueous extract treatment. Methanolic extract showed higher activity in increasing kidney glutathione (P

  4. Decision making as a predictor of first ecstasy use: a prospective study

    Schilt, T.; Goudriaan, A.E.; Koeter, M.W.; van den Brink, W.; Schmand, B.


    Rationale: Ecstasy (±3,4-methylenedioxymethamphetamine) is a widely used recreational drug that may damage the serotonin system and may entail neuropsychological dysfunctions. Few studies investigated predictors for ecstasy use. Self-reported impulsivity does not predict the initiation of ecstasy us

  5. Ecstasy use and self-reported depression, impulsivity, and sensation seeking: a prospective cohort study

    M.M.L. de Win; T. Schilt; L. Reneman; H. Vervaeke; G. Jager; S. Dijkink; J. Booij; W. van den Brink


    Although there are indications that ecstasy users have higher Levels of depression, impulsivity, and sensation seeking, it is unknown whether these are consequences of ecstasy use or predisposing factors for starting ecstasy use. We prospectively assessed the predictive value of depression, impulsiv

  6. Specific effects of ecstasy and other illicit drugs on cognition in poly-substance users

    T. Schilt; M.M.L. de Win; G. Jager; M.W. Koeter; N.F. Ramsey; B. Schmand; W. van den Brink


    Background. A large number of studies, reviews and meta-analyses have reported cognitive deficits in ecstasy users. However most ecstasy users are polydrug users, and therefore it cannot be excluded that these deficits are (partly) the result of drugs other than ecstasy. The current study, part of t

  7. Decision making as a predictor of first ecstasy use: a prospective study

    Schilt, T.; Goudriaan, A.E.; Koeter, M.W.; van den Brink, W.; Schmand, B.


    Rationale: Ecstasy (±3,4-methylenedioxymethamphetamine) is a widely used recreational drug that may damage the serotonin system and may entail neuropsychological dysfunctions. Few studies investigated predictors for ecstasy use. Self-reported impulsivity does not predict the initiation of ecstasy

  8. A structured review of reasons for ecstasy use and related behaviours: pointers for future research

    Kok Gerjo


    Full Text Available Abstract Background While the health risks of using ecstasy warrant intervention development, a recent meta-analysis of determinants of ecstasy use identified a number of lacunae in the literature. Specifically, no studies were included that address behaviours other than 'using ecstasy' (e.g. 'trying out ecstasy' or 'ceasing ecstasy use'. However, because meta-analyses aim to integrate study results quantitatively, the resulting rigid exclusion criteria cause many studies to be discarded on the basis of their qualitative methodology. Such qualitative studies may nonetheless provide valuable insights to guide future research. To provide an overview of these insights regarding ecstasy use, the current study summarizes and combines what is known from qualitative and exploratory quantitative literature on ecstasy use. Methods The databases PsycINFO and MedLine were searched for publications reporting reasons for ecstasy use and related behaviour, and the results were structured and discussed per behaviour and compared over behaviours. Results Two main categories of reasons were found. The first category comprised reasons to start using ecstasy, use ecstasy, use ecstasy more often, and refrain from ceasing ecstasy use. The second category comprised reasons to refrain from starting to use ecstasy, use less ecstasy, and cease using ecstasy. Reasons for related behaviours within each of these two categories appear to differ, but not as substantially as between the two categories. A large number of reasons that were not yet explored in quantitative research emerged. Conclusion The current summary and combination of exploratory studies yields useful lists of reasons for each behaviour. Before these lists can inform interventions, however, they beg quantitative verification. Also, similarity of determinant configurations of different behaviours can be assessed by addressing determinants of several behaviours in one study. Another important finding is that

  9. MDMA: a social drug in a social context

    Kirkpatrick, Matthew G.; de Wit, Harriet


    Rationale The drug ±3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”, “molly”) is thought to produce pro-social effects and enhance social interaction. However, in most laboratory studies to date, the participants have been tested under non-social conditions, which may not simulate the effects the drug produces in more naturalistic social settings. Methods Healthy experienced MDMA users participated in three laboratory sessions in which they received MDMA (0.5 or 1.0 mg/kg or placebo; double blind). They were randomly assigned to one of three social conditions, in which they were tested alone (SOL; N=10), in the presence of a research assistant (RAP; N=11) or in the presence of another participant who also received the drug (OPP; N=11). Results As expected, MDMA increased heart rate and blood pressure, and produced positive subjective effects in all three groups. It also increased ratings of attractiveness of another person and increased social interaction in RAP and OPP. The social context affected certain responses to the drug. The effects of MDMA were greater in the OPP condition, compared to the SOL or RAP conditions, on measures of “feel drug”, “dizzy” and on cardiovascular measures. But responses to the drug on other measures, including social behavior, did not differ across the conditions. Conclusions These findings provide some support for the idea that drugs produce greater effects when they are used in the presence of other drug users. However, the influence of the social context was modest, and it remains to be determined whether other variables related to social context would substantially alter the effects of MDMA or other drugs. PMID:25281223

  10. Regular figures

    Tóth, L Fejes; Ulam, S; Stark, M


    Regular Figures concerns the systematology and genetics of regular figures. The first part of the book deals with the classical theory of the regular figures. This topic includes description of plane ornaments, spherical arrangements, hyperbolic tessellations, polyhedral, and regular polytopes. The problem of geometry of the sphere and the two-dimensional hyperbolic space are considered. Classical theory is explained as describing all possible symmetrical groupings in different spaces of constant curvature. The second part deals with the genetics of the regular figures and the inequalities fo

  11. Spontaneous pneumomediastinum following ecstasy ingestion and sexual intercourse.

    Stull, B W


    Ecstasy is an illegal drug that has become widely used among adolescents and young adults. It is used recreationally for its stimulant and sensory-altering properties. Serious adverse effects are well documented and include arrhythmias, hyperthermia, seizures and long-term neuropsychiatric effects. A handful of previous case reports have recognised a relationship between ecstasy use and spontaneous pneumomediastinum, but an underlying mechanism has been difficult to identify. This report describes a 21-year-old man who presented with chest pain and dysphagia 1 day after using ecstasy. He was subsequently found to have both mediastinal and retropharyngeal emphysema. It is suspected that the underlying aetiology of the findings in this case was sexual intercourse.

  12. Differential effects of ecstasy on short-term and working memory: a meta-analysis.

    Nulsen, Claire E; Fox, Allison M; Hammond, Geoffrey R


    Quantitative analysis of studies examining the effect of ecstasy on short-term and working memory in the verbal and visuo-spatial domain was undertaken. Thirty verbal short-term memory, 22 verbal working memory, 12 visuospatial short-term memory and 9 visuospatial working memory studies met inclusion criteria. Ecstasy users performed significantly worse in all memory domains, both in studies using drug-naïve controls and studies using polydrug controls. These results are consistent with previous meta-analytic findings that ecstasy use is associated with impaired short-term memory function. Lifetime ecstasy consumption predicted effect size in working memory but not in short-term memory. The current meta-analysis adds to the literature by showing that ecstasy use in humans is also associated with impaired working memory, and that this impairment is related to total lifetime ecstasy consumption. These findings highlight the long-term, cumulative behavioral consequences associated with ecstasy use in humans.

  13. Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture.

    Harvey, Eric L; Baker, Lisa E


    Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. Dose-response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture. These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

  14. A method of conducting therapeutic sessions with MDMA.

    Greer, G R; Tolbert, R


    A method for preparing clients and conducting therapeutic sessions with 3,4-methylenedioxymethamphetamine (MDMA) is described, with emphasis on the need for careful attention to the mental set of therapists and clients and the setting of the session. The therapists' belief was that MDMA inhibited the fear response to a perceived emotional threat, allowing the client to place the emotional sequelae of past experiences into a more realistic perspective in their current emotional lives and relationships. Clients were carefully screened and prepared until they had a clear purpose for the session, including a willingness to experience and to learn from anything that might happen. Sympathomimetic effects of MDMA determined the medical contraindications, and clients with histories of serious functional psychiatric impairments were excluded. Total doses of 75-150 mg, plus 50 mg if requested later, were administered, followed by clients lying down and listening to music with eyeshades and headphones during the peak MDMA effect. Screening and follow-up questionnaires were utilized. Two case histories are presented: a man achieving relief of pain from multiple myeloma, and a woman finding relief from problems as the daughter of Holocaust survivors. Use of consciousness-altering drugs in other contexts is discussed.

  15. Behavioral and neurochemical effects of prenatal methylenedioxymethamphetamine (MDMA) exposure in rats.

    St Omer, V E; Ali, S F; Holson, R R; Duhart, H M; Scalzo, F M; Slikker, W


    MDMA is a hallucinogenic drug that is used by the general public as a recreational drug of abuse. The neurobehavioral consequences of prenatal MDMA exposure are unknown. Groups of pregnant rats were gavaged with 0, 2.5, or 10 mg/kg MDMA during gestation on alternate gestational days 6-18. Gestational duration, litter size, neonatal birth weights and physical appearance at birth were unaffected by MDMA treatments. Pregnancy weight gain was significantly reduced by MDMA treatment. Progeny growth, maturational parameters (eye opening and incisor eruption times), surface righting reflex, swimming performance, forelimb grip strength, milk-induced behaviors, passive avoidance behavior, figure-8 maze activity over 48 hours, the density of brain serotonin (5-HT) uptake sites, and brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were unaffected by MDMA treatments. Olfactory discrimination on postnatal days (PND) 9-11 was enhanced in both male and female MDMA-treated progeny, while negative geotaxis (PND 7-10) was delayed in female pups. In contrast to progeny, MDMA caused dose-dependent decreases in 5-HT and 5-HIAA levels in discrete brain areas of the dam. It is concluded that prenatal exposure to MDMA at the levels used here produces only subtle behavioral alterations in developing rats. The dam is more at risk for MDMA-induced 5-HT depletion than is the conceptus.

  16. Desenvolvimento e validação de um método cromatográfico em fase gasosa para análise da 3,4-metilenodioximetanfetamina (ecstasy e outros derivados anfetamínicos em comprimidos Development and validation of a gas chromatography method for determination of ecstasy and amphetamines derivatives in tablets

    Marcelo Carvalho Lasmar


    Full Text Available O uso abusivo das anfetaminas e seus derivados vêm aumentando dramaticamente nos últimos anos em diversas regiões do mundo, notando-se especial utilização do Ecstasy. A análise de amostras da droga apreendidas nas ruas evidenciou, além da presença de MDMA (3,4-metilenodioximetanfetamina, componente principal da droga, outras feniletilaminas, como a MDA (3,4-metilenodioxanfetamina e MDEA (metilenodioximetiletilanfetamina este último também conhecido como a droga Eve, ainda pouco difundida no Brasil. O objetivo do presente trabalho foi desenvolver e validar um método analítico confiável, prático e acessível aos laboratórios de toxicologia, de médio e pequeno porte, no Brasil e em países em desenvolvimento, para identificação separada do MDMA, MDA e MDEA. A cromatografia em fase gasosa utilizando-se coluna capilar e detector de ionização de chama foi a técnica escolhida. O método analítico apresentou para os três analitos de interesse, faixa ampla de linearidade (1,0 a 500,0 µg/mL; limites de quantificação de 1,0 µg/mL e coeficientes de variação intra e interensaio inferiores a 9,5%. Os limites de detecção estabelecidos foram 0,7 µg/mL, 0,8 µg/mL e 0,6 µg/mL, respectivamente para o MDMA, MDA e MDEA. O método foi seletivo na presença de epinefrina, cocaína, anfetamina, ácido acetilsalisílico, metanfetamina, ácido dietilbarbitúrico, p-aminobenzoil dietilbarbitúrico, paracetamol e cafeína.The abusive use of the amphetamine derivative ecsyasy in the world come increasing in the last years. Many tablets samples kept on the streets shown the presence not only of the MDMA- 3,4-methylenedioxymethamphetamine, the main drug component but also of the MDA - 3,4- methylenedioxyamphetamine and MDEA - 3,4-methylenedioxymethylethylamphetamine. The present study sought to develop and validate an analytical method for determination of MDMA, MDA and MDEA in tablets to be accessible for the most small or medium

  17. From religious ecstasy to ecstasy pills: a symbolic and performative analysis of electronic music festivals

    Tiago Coutinho


    Full Text Available This article looks to analyze the process through which eastern cosmological elements and religious practices acquire new meanings as they take on fresh uses in western festive contexts, as well as examine the symbolic and performative dimensions of the phenomenon in question. Electronic music festivals suggest a reading of eastern religious factors that serve as a reference to their 'origin myth.' The ethnographic data reveals a new form of obtaining ecstasy via music, performances, 'natural' ambients and altered states of consciousness. The appeal to transcendence is the direct result of western re-workings of Indian religious practices - especially those proposed by the spiritual leader Osho, who formed a cosmology based on fragments taken out of their 'original' context and given meaning in the life of those who adopt the Sannyasalifestyle.

  18. Teacher as Writer: Remembering the Agony, Sharing the Ecstasy.

    Augsburger, Deborah J.


    Argues that teachers who write are in a better position to guide students, provide useful feedback, and show the real value of writing. Discusses remembering the agony, sharing the ecstasy, giving authentic feedback, growing a community of writers, and remembering the reason people bother to write at all. (SR)

  19. Extensive Subcutaneous Emphysema and Pneumomediastinum after Ecstasy Ingestion

    A. Gungadeen


    Full Text Available Objective. To present a rare case of extensive subcutaneous emphysema and spontaneous pneumomediastinum following ingestion of Ecstasy in a young adult. We also review the relevant literature and discuss how this case supplements it. Case Report. We report a case of a 19-year-old man with a history of painless neck and chest swelling, and no chest pain or breathlessness, after consuming Ecstasy tablets. Radiological imaging showed evidence of pneumomediastinum and extensive subcutaneous emphysema. The patient remained well under observation and his symptoms improved with conservative management. Conclusions. Subcutaneous emphysema and pneumomediastinum after Ecstasy ingestion is uncommon. Cases are often referred to the otolaryngologist as they can present with neck and throat symptoms. Our case showed that the severity of symptoms may not correlate with severity of the anatomical abnormality and that pneumomediastinum should be suspected in Ecstasy users who present with neck swelling despite the absence of chest symptoms. Although all cases reported so far resolved with conservative management, it is important to perform simple investigations to exclude coexisting serious pathology.

  20. Functional MRI studies in human Ecstasy and cannabis users

    Jager, G.


    Cannabis and ecstasy are among the most widely used illicit drugs in the world. However, there are substantial concerns about their neurotoxic potential for brain and brain function. Despite previous research, some crucial questions regarding the causality, course and clinical relevance have remaine

  1. [Pneumorachis and pneumopericardium after ecstasy use: an uncommon complication

    Kubbenga, I.E.; Postma, N.; Ramakers, B.P.C.


    BACKGROUND: Over the past few years there has been an increase in the use of ecstasy among the Dutch population. A number of complications are associated with this drug, hyperthermia being the most well-known. A less commonly-occurring complication is pneumomediastinum. CASE DESCRIPTION: A

  2. The Impact of Positive and Negative Ecstasy-Related Information on Ecstasy Use among College Students: Results of a Longitudinal Study

    Vincent, Kathryn B.; Caldeira, Kimberly M.; O'Grady, Kevin E.; Wish, Eric D.; Arria, Amelia M.


    Aims: To: (1) estimate the proportion of students exposed to specific types of information regarding the positive and negative effects of ecstasy, (2) test models that quantified the relationship between exposure to these messages and subsequent ecstasy use, controlling for peer drug use and sensation-seeking. Methods: As part of the College Life…

  3. Schizophrenia-like disruptions of sensory gating by serotonin receptor stimulation in rats: effect of MDMA, DOI and 8-OH-DPAT.

    Thwaites, Shane J; Gogos, Andrea; Van den Buuse, Maarten


    Schizophrenia pathophysiology is associated with alterations in several neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT). Schizophrenia patients also have disruptions in sensory gating, a brain information filtering mechanism in response to repeated sensory stimuli. Dopamine and glutamate have been implicated in sensory gating; however, little is known about the contribution of serotonin. We therefore investigated the effects of several psychoactive compounds that alter serotonergic neuronal activity on event-related potentials (ERP) to paired auditory pulses. Male Sprague-Dawley rats were implanted with cortical surface electrodes to measure ERPs to 150 presentations of two 85 dB bursts of white noise, 500 ms apart (S1 and S2). Saline-treated animals suppressed the response to S2 to less than 50% of S1. In contrast, treatment with the serotonin releaser, MDMA (ecstasy; 2.0mg/kg), the 5-HT2A/2C receptor agonist, DOI (0.5mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT (0.5mg/kg), caused an increase in S2/S1 ratios. Analysis of waveform components suggested that the S2/S1 ratio disruption by MDMA was due to subtle effects on the ERPs to S1 and S2; DOI caused the disruption primarily by reducing the ERP to S1; 8-OH-DPAT-induced disruptions were due to an increase in the ERP to S2. These results show that 5-HT receptor stimulation alters S2/S1 ERP ratios in rats. These results may help to elucidate the sensory gating deficits observed in schizophrenia patients.

  4. NeuN Expression Alterations in the Hippocampus Following Ecstasy Treatment

    Ghasemi Moravej


    Full Text Available Background The administration of 3-4-methylenedioxymethamphetamine (MDMA leads to learning and memory impairment. Objectives Due to the effect of neurogenesis on memory and learning, in this study, we investigated the effects of MDMA on NeuN expression (a marker of neurogenesis in the hippocampus. Methods Adult male Wistar rats (weighing 200 - 250 g received a single intraperitoneal dose of 10 mg/kg of MDMA or were left undisrupted. The expression of NeuN was assessed using the immunohistochemistry method 7, 14, 28, and 60 days following MDMA administration. Results Our results showed that MDMA administration caused a decrease in NeuN expression in the experimental group compared with the control group. Conclusions These results suggest a negative correlation between MDMA administration and adult hippocampal neurogenesis.

  5. Molecularly imprinted-solid phase extraction combined with simultaneous derivatization and dispersive liquid-liquid microextraction for selective extraction and preconcentration of methamphetamine and ecstasy from urine samples followed by gas chromatography.

    Djozan, Djavanshir; Farajzadeh, Mir Ali; Sorouraddin, Saeed Mohammad; Baheri, Tahmineh


    In this study, a developed technique was reported for extraction and pre-concentration of methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) from urine samples using molecularly imprinted-solid phase extraction (MISPE) along with simultaneous derivatization and dispersive liquid-liquid microextraction (DLLME). Molecularly imprinted microspheres as sorbent in solid phase extraction (SPE) procedure were synthesized using precipitation polymerization with MAMP as the template. Aqueous solution of the target analytes was passed through MAMP-MIP cartridge and the adsorbed analytes were then eluted with methanol. The collected eluate was mixed with butylchloroformate which served as the derivatization reagent as well as the extraction solvent. The mixture was immediately injected into deionized water. After centrifugation, 1 μL of the settled organic phase was injected into gas chromatography-flame ionization detection (GC-FID) or gas chromatography-mass spectrometry (GC-MS). Various experimental parameters affecting the performance of both of the steps (MISPE and DLLME) were thoroughly investigated. The calibration graphs were linear in the ranges of 10-1500 ng mL(-1) (MAMP) and 50-1500 ng mL(-1) (MDMA), and the detection limits (LODs) were 2 and 18 ng mL(-1), respectively. The relative standard deviations (%RSDs) obtained for six repeated experiments (100 ng mL(-1) of each drug) were 5.1% and 6.8% for MAMP and MDMA, respectively. The relative recoveries obtained for the analytes in human urine samples, spiked with different levels of each drug, were within the range of 80-88%.

  6. Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA.

    Mithoefer, Michael C; Grob, Charles S; Brewerton, Timothy D


    4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.

  7. Attitude towards and use of ecstasy in medical university interns' based on HBM.

    Baghianimoghadam, M H; Mazloomy Mahmoodabad, S S; Mohammadi, S; Baghianimoghadam, B


    Using a self-reported questionnaire, 130 Yazd Medical University students were surveyed about their knowledge towards ecstasy and their use of ecstasy based on Health Belief Model. The age range was 18-31 years. Approximately, 23% of students had seen an ecstasy tablet, 6 (4.6%) had used ecstasy (2 female and 4 male), 4 of them lived in a dormitory and 2 were tenants. The levels of knowledge, perceived barrier and perceived benefit of students who had used ecstasy were lower than those who hadn't used ecstasy. There was a significant difference between the knowledge, perceived barrier and perceived benefit of samples and use of ecstasy (p university: 12.3%; friends: 12.3%; newspapers/magazine articles: 7.7%. The data revealed that the knowledge of participants about ecstasy was low (mean = 27.69 +/- 3.53 out of 48). The mean grade score of knowledge of males was more than females. A survey in Kerman (Iran) showed that the knowledge of general practitioners about ecstasy was lower than 50% and the knowledge of males was more than females.

  8. What’s in a Label? Ecstasy Sellers’ Perceptions of Pill Brands†

    Duterte, Micheline; Jacinto, Camille; Sales, Paloma; Murphy, Sheigla


    This article presents selected findings from a qualitative study of Ecstasy sellers and their sales practices, knowledge of distribution networks, buyer-seller relationships, and self-reported drug use. In-depth interviews were conducted with 80 men and women who had sold five or more hits of Ecstasy five or more times in the six months prior to the interview. Study participants described their perceptions of the various types of Ecstasy they had distributed or used themselves. The participants had experience with a variety of Ecstasy labels, from the popular “Blue Dolphin” tablets to the powdered form called “Molly.” We tracked pill brand mentions on Ecstasy-related websites to compare with interviewees’ descriptions of Ecstasy brands. This study examines Ecstasy sellers’ ideas about the role of brand names in Ecstasy markets and their relationship to their beliefs about different types of Ecstasy’s purity and quality. We demonstrate that considering Ecstasy branding increases our understanding of buyer and seller relationships. PMID:19455907

  9. In-sample derivatization-solid-phase microextraction of amphetamines and ecstasy related stimulants from water and urine.

    Racamonde, Inés; Rodil, Rosario; Quintana, José Benito; Cela, Rafael


    A solid-phase microextraction (SPME) method for the determination of five amphetamine type stimulants (ATSs) in water and urine samples is presented. Analytes were simultaneously derivatized with iso-butyl chloroformate (iBCF) in the aqueous sample while being extracted, improving in this way the extractability of ATSs and permitting their determination by gas chromatography-mass spectrometry (GC-MS). The SPME procedure was carefully optimized in order to achieve adequate limits of detection (LODs) for environmental concentrations. Hence, different operational parameters were considered: type of SPME coating, ionic strength, basic catalyzer and derivatizing agent amount, extraction time and temperature. The final SPME procedure consists into the extraction of 100mL of sample containing 2 g of dipotassium monohydrogen phosphate trihydrate and 100 μL of iBCF (1:1 in acetonitrile), for 40 min at 60°C with a polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber. Under these conditions, LODs in wastewater ranged from 0.4 to 2 ng L(-1), relative recoveries in the 84-114% range and relative standard deviations (RSD) lower than 15% were obtained. The application of the method to wastewater and river water samples showed the ecstasy ATS, 3,4-methylenedioxymethamphetamine (MDMA), as the most frequently detected, followed by methamphetamine, in concentrations around 20 ng L(-1). Finally, the method was downscaled and also validated with urine samples, proving its good performance with this matrix too: RSD<11%, recoveries in the 98-110% range and LODs lower than 0.1 μg L(-1).

  10. Spontaneous pneumomediastinum and epidural pneumatosis after oral ecstasy consumption.

    Clause, A L; Coche, E; Hantson, P; Jacquet, L M


    A 19-year-old man was admitted with acute dyspnoea. Physical examination revealed subcutaneous emphysema in the cervical and thoracic area. This was further confirmed by the total body computed tomography that also demonstrated mediastinal emphysema. Epidural pneumatosis of the thoracis spine was also evident. There was no history of trauma, but well of a recent oral ecstasy consumption during a techno rave party, associated with intense dancing and jumping. Clinical course was favourable with conservative therapy.

  11. The Siberian Shaman’s technique of ecstasy

    Anna-Leena Siikala


    Changes in the field of observation and body image, attenuated grasp of reality and self-control, which may lead to identification with authority in the case of the shaman with supranormal powers, are all identifying features of shamanic ecstasy. It also appears that some of the basic elements of the shamanic tradition can be explained on the basis of typical marks of identification of altered states of consciousness. A sense of depersonalization and transcendence may in itself act as an impe...

  12. The Siberian Shaman’s technique of ecstasy

    Anna-Leena Siikala


    Full Text Available Changes in the field of observation and body image, attenuated grasp of reality and self-control, which may lead to identification with authority in the case of the shaman with supranormal powers, are all identifying features of shamanic ecstasy. It also appears that some of the basic elements of the shamanic tradition can be explained on the basis of typical marks of identification of altered states of consciousness. A sense of depersonalization and transcendence may in itself act as an impetus to cosmic journey fantasies. Without doubt, such feelings are at the very heart of the tradition containing the schism between mind and body. Thus, by placing the shamanic technique of ecstasy beside parallel modes of behaviour, possibly of different cultural background, we discover the guide lines for analysing its basic psychophysical properties. When studying a phenomenon such as shamanism, where the method of inducing trance is marked by the occurrence of certain common features and whose culturally-bound meaning and social function are, broadly speaking, uniform, we may assume that despite individual variation the basic mechanism of the technique of ecstasy may be delineated. What, then, is the ideal process of the shamanic trance technique? What factors exert particular pressure on the behaviour of the shaman? Shamanic practice differ from other means of attaining ecstasy with its emphasis on the ritual role-taking technique aimed at the supranormal counter-roles, the "spirit-helpers". The shaman's generalized reality orientation is cut off by means of suitable ritual requisites, the extinguishing of the lights and the noise of intensified drumming. Its place is taken by special orientation, a world created by the shamanic tradition, fantasies of supranormal beings and their dwelling places. The shaman actualises one spirit role after another according to a set pattern.

  13. Adaptive regularization

    Hansen, Lars Kai; Rasmussen, Carl Edward; Svarer, C.


    Regularization, e.g., in the form of weight decay, is important for training and optimization of neural network architectures. In this work the authors provide a tool based on asymptotic sampling theory, for iterative estimation of weight decay parameters. The basic idea is to do a gradient descent...... in the estimated generalization error with respect to the regularization parameters. The scheme is implemented in the authors' Designer Net framework for network training and pruning, i.e., is based on the diagonal Hessian approximation. The scheme does not require essential computational overhead in addition...... to what is needed for training and pruning. The viability of the approach is demonstrated in an experiment concerning prediction of the chaotic Mackey-Glass series. The authors find that the optimized weight decays are relatively large for densely connected networks in the initial pruning phase, while...

  14. Sustained effects of ecstasy on the human brain : a prospective neuroimaging study in novel users

    de Win, Maartje M. L.; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Silvia D.; den Heeten, Gerard J.; van den Brink, Wim


    Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT

  15. Sustained Effects of Ecstasy on the Human Brain: A Prospective Neuroimaging Study in Novel Users

    de Win, Maartje M. L.; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Christina; Olabarriaga, Silvia D.; den Heeten, Gerard J.; van den Brink, Wim


    Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained…

  16. Correlates of Ecstasy Use among Students Surveyed through the 1997 College Alcohol Study.

    Yacoubian, George S., Jr.


    The drug-using behaviors of 14,520 college students were examined with data collected through the 1997 College Alcohol Study. Prevalence estimates of ecstasy use were generated and associations between ecstasy use, demographic characteristics, and alcohol and other drug use were explored. Implications for these findings are discussed. (Contains 24…

  17. Whats the Rap about Ecstasy? Popular Music Lyrics and Drug Trends among American Youth

    Diamond, Sarah; Bermudez, Rey; Schensul, Jean


    Trends in ecstasy use in America during the past decade were reflected in mainstream, American rap-music lyrics between 1996 and 2003. Drawing on communication and cultural studies theory, this article provides a content analysis of 69 rap songs mentioning the club drug ecstasy. The songs are coded according to whether they contain positive, mixed…

  18. MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

    Drew J. Puxty


    Full Text Available Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol, which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg, combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg. Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations. Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

  19. Memory and mood during MDMA intoxication, with and without memantine pretreatment.

    de Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Heckman, P; de la Torre, R; Farre, M; Ramaekers, J G


    Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning Task. Profile of Mood State and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigour, arousal, elation) and negative mood effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans. This article is part of the Special Issue entitled 'CNS Stimulants'.

  20. Eroticism in group psychotherapy: psychoanalytic reflections on desire, agony, and ecstasy.

    Tylim, Isaac


    To fully understand the complexities of eroticism in groups, it may be necessary to review a conceptual differentiation of desire and its allies: agony and ecstasy. This article suggests that psychoanalytic group psychotherapy is made for neither agony nor ecstasy. Sexual excitement maybe; eroticism and desire, yes; agony and ecstasy, no. While agony or ecstasy imply a threat to the survival of the group, eroticism and desire reaffirm its existence. In this manner the group may be converted into a theater where desire may be celebrated, while the threat of being dissolved in the depths or exaltation of agony and ecstasy is elaborated and worked through: "Desire is desire only if it succeeds in postponing something".

  1. Plasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions

    Samyn, N; De Boeck, G; Wood, M; Lamers, CTJ; De Waard, D; Brookhuis, KA; Verstraete, AG; Riedel, WJ


    In a double-blind placebo controlled study on psychomotor skills important for car driving (Study 1), a 75 mg dose of 3,4methylenedioxymethamphetamine (MDMA) was administered orally to 12 healthy Volunteers who were known to be recreational MDMA-users. Toxicokinetic data were gathered by analysis of

  2. Regular polytopes

    Coxeter, H S M


    Polytopes are geometrical figures bounded by portions of lines, planes, or hyperplanes. In plane (two dimensional) geometry, they are known as polygons and comprise such figures as triangles, squares, pentagons, etc. In solid (three dimensional) geometry they are known as polyhedra and include such figures as tetrahedra (a type of pyramid), cubes, icosahedra, and many more; the possibilities, in fact, are infinite! H. S. M. Coxeter's book is the foremost book available on regular polyhedra, incorporating not only the ancient Greek work on the subject, but also the vast amount of information

  3. Organic impurity profiling of 3,4-methylenedioxymethamphetamine (MDMA) synthesised from catechol.

    Heather, Erin; Shimmon, Ronald; McDonagh, Andrew M


    This work examines the organic impurity profile of 3,4-methylenedioxymethamphetamine (MDMA) that has been synthesised from catechol (1,2-dihydroxybenzene), a common chemical reagent available in industrial quantities. The synthesis of MDMA from catechol proceeded via the common MDMA precursor safrole. Methylenation of catechol yielded 1,3-benzodioxole, which was brominated and then reacted with magnesium allyl bromide to form safrole. Eight organic impurities were identified in the synthetic safrole. Safrole was then converted to 3,4-methylenedioxyphenyl-2-propanone (MDP2P) using two synthetic methods: Wacker oxidation (Route 1) and an isomerisation/peracid oxidation/acid dehydration method (Route 2). MDMA was then synthesised by reductive amination of MDP2P. Thirteen organic impurities were identified in MDMA synthesised via Route 1 and eleven organic impurities were identified in MDMA synthesised via Route 2. Overall, organic impurities in MDMA prepared from catechol indicated that synthetic safrole was used in the synthesis. The impurities also indicated which of the two synthetic routes was utilised.

  4. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M


    The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

  5. Memory and mood during the night and in the morning after repeated evening doses of MDMA.

    Kuypers, K P C; Wingen, M; Ramaekers, J G


    Previously it has been shown that MDMA causes memory impairment during daytime testing. However, MDMA is usually taken in the evening or during the night. In addition, it is known that sleep deprivation also causes memory impairment. The present study aimed to assess whether evening doses of MDMA added to, or interacted with the memory impairment due to sleep deprivation. Fourteen healthy subjects participated in a double-blind, placebo-controlled, two-way cross-over study. Treatments consisted of MDMA 75 and 50 mg divided over the evening or double placebo. Memory tests and subjective measures of mood were conducted at baseline and three times post dosing that is at 6.30 pm, 9.30 pm, 1.30 am and 7 am, respectively -1.5, 1.5, 5.5 and 11 h relative to drug intake (first dose). Memory performance detoriated progessively over time as a function of sleep loss, independent of treatment. MDMA added to this impairment as indicated by a significant main effect of MDMA on verbal and spatial memory performance. Mood ratings and response speed revealed an MDMA by Time interaction. After administration of MDMA response speed improved and feelings of vigor, friendliness, elation, anxiety, confusion, arousal and positive mood increased in magnitude during the night, while all these parameters returned to placebo-like levels on the final morning session. It is concluded that evening doses of MDMA selectively impair memory performance, and that this impairment is additional to the effect of sleep deprivation on memory performance.

  6. Methamphetamine and MDMA: ‘Safe’ drugs of abuse

    Allana M. Krolikowski


    Full Text Available Methamphetamine and MDMA have been called safe drugs of abuse. Worldwide there is an increased consumption of these drugs, which has become a focus of research in South Africa. As the number of methamphetamine users has increased in many African countries, it is essential that emergency care practitioners are able to diagnose and manage intoxication with methamphetamine, MDMA, and other derivatives. The most common presentations include restlessness, agitation, hypertension, tachycardia, and headache while hyperthermia, hyponatraemia, and rhabdomyolysis are among the most common serious complications. Most deaths are secondary to hyperthermia complicated by multiple organ failure. A number of laboratory analyses should be obtained if locally available. We provide a review of the current recommended general and specific management approaches. Benzodiazepines are the first line therapy for hyperthermia, agitation, critical hypertension, and seizures. Patients with serious complications are best managed in an intensive care unit if available. Emergency centres should create protocols and/or further train staff in the recognition and management of intoxication with these ‘not so safe’ drugs.

  7. Subacute effects of ecstasy on mood: an exploration of associated risk factors.

    Scott, Rebecca M; Hides, Leanne; Allen, J Sabura; Lubman, Dan I


    Ecstasy use may result in lowered mood, anxiety or aggression in the days following use. Yet, few studies have investigated what factors increase the risk of experiencing such symptoms. Ecstasy users (at least once in the last 12 months) who subsequently took ecstasy (n=35) over the period of one week, were compared on measures of mood, sleep, stress and drug use, with those who abstained from ecstasy (n=21) that week. Measures were administered the week prior to ecstasy use and one and three days following use, or the equivalent day for abstainers. Mood symptoms were assessed using the Kessler-10 self-report psychological distress scale, a subjective mood rating (1-10), and using the depression, anxiety and hostility items from the clinician-rated Brief Psychiatric Rating Scale. Timeline Followback methods were used to collect information on drug use and life stress in the past month. Self-reported sleep quality was also assessed. Ecstasy use was not associated with subacute depressive, anxiety or aggressive symptoms. Rather, lowered mood and increased psychological distress were associated with self-reported hours and quality of sleep obtained during the three-day follow-up. These findings highlight the importance of considering sleep disruption in understanding the short-term mood effects of ecstasy use.

  8. Brief interventions to reduce Ecstasy use: a multi-site randomized controlled trial.

    Norberg, Melissa M; Hides, Leanne; Olivier, Jake; Khawar, Laila; McKetin, Rebecca; Copeland, Jan


    Studies examining the ability of motivational enhancement therapy (MET) to augment education provision among ecstasy users have produced mixed results and none have examined whether treatment fidelity was related to ecstasy use outcomes. The primary objectives of this multi-site, parallel, two-group randomized controlled trial were to determine if a single-session of MET could instill greater commitment to change and reduce ecstasy use and related problems more so than an education-only intervention and whether MET sessions delivered with higher treatment fidelity are associated with better outcomes. The secondary objective was to assess participants' satisfaction with their assigned interventions. Participants (N=174; Mage=23.62) at two Australian universities were allocated randomly to receive a 15-minute educational session on ecstasy use (n=85) or a 50-minute session of MET that included an educational component (n=89). Primary outcomes were assessed at baseline, and then at 4-, 16-, and 24-weeks postbaseline, while the secondary outcome measure was assessed 4-weeks postbaseline by researchers blind to treatment allocation. Overall, the treatment fidelity was acceptable to good in the MET condition. There were no statistical differences at follow-up between the groups on the primary outcomes of ecstasy use, ecstasy-related problems, and commitment to change. Both intervention groups reported a 50% reduction in their ecstasy use and a 20% reduction in the severity of their ecstasy-related problems at the 24-week follow up. Commitment to change slightly improved for both groups (9%-17%). Despite the lack of between-group statistical differences on primary outcomes, participants who received a single session of MET were slightly more satisfied with their intervention than those who received education only. MI fidelity was not associated with ecstasy use outcomes. Given these findings, future research should focus on examining mechanisms of change. Such work may

  9. Pseudorotaxane capped mesoporous silica nanoparticles for 3,4-methylenedioxymethamphetamine (MDMA) detection in water

    Lozano-Torres, Beatriz; Pascual, Lluís; Bernardos, Andrea


    Mesoporous silica nanoparticles loaded with fluorescein and capped by a pseudorotaxane, formed between a naphthalene derivative and cyclobis(paraquat-p-phenylene) (CBPQT4+), were used for the selective and sensitive fluorogenic detection of 3,4-methylenedioxymethamphetamine (MDMA)....

  10. A survey of Ecstasy use among 15-25 year-olds in five areas of Tehran

    Barooni Sh


    Full Text Available Background: To eradicate a problem such as drug abuse, we need thorough knowledge of the problem and its epidemiological aspects. In response to increasing ecstasy abuse among youth, as noted by the increase in related health issues at emergency clinics, we performed this epidemiologic study on ecstasy use in Tehran.Methods: In this cross-sectional study, including 1,903 youth aged 15-25 years, at different coffee shops in Tehran, Iran, subjects filled out questionnaires to evaluate the prevalence of ecstasy use with regard to gender, age, family income, level of education, psychological state (Beck test, acute complications of ecstasy use, as well as manner and place of ecstasy use and reason for repeated ecstasy use. Information was gathered from September 2004 to January 2005, using simple nonprobable sampling.Results: The prevalence of ecstasy abuse among our study population was 18.5%, which meaningfully correlated with gender (male, education level (undergraduate degree, family income (high, drug abuse and Beck test score (high. The mean age of ecstasy abusers was 21.3 years (SD: 2.65, which wasn't statistically different than the study population as a whole and the portion that did not use ecstasy. Tablet was the most common form of ecstasy usage (97.1%. In this study population, 91.4% had heard of the ecstasy name, and 83.7% were familiar with its use. The most common site of usage was in parties (85.7% and in group forms (84%. Of all the users, 30% stated the reason for repeat ecstasy use was their friends' insistence, 38.8% expressed emotional need, 37.7% had no reason, whereas 6.6% felt a physical need and 1.7% repeatedly used ecstasy to prevent withdrawal symptomsConclusion: Some studies have reported that drug abusing friends are the basic cause of drug abuse. In this study, the ecstasy users admitted that the influence of friends and emotional need were the causes of their repeat use. Remarkably, these subjects report

  11. Effects of (± 3,4-Methylenedioxymethamphetamine (MDMA on Sleep and Circadian Rhythms

    Una D. McCann


    Full Text Available Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA, may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in normal sleep regulation. In particular, MDMA has been found to damage brain serotonin (5-HT neurons in a variety of animal species, including nonhuman primates, with growing evidence that humans are also susceptible to MDMA-induced brain 5-HT neurotoxicity. 5-HT is an important modulator of sleep and circadian rhythms and, therefore, individuals who sustain MDMA-induced 5-HT neurotoxicity may be at risk for developing chronic abnormalities in sleep and circadian patterns. In turn, such abnormalities could play a significant role in other alterations reported in abstinent in MDMA users (e.g., memory disturbance. This paper will review preclinical and clinical studies that have explored the effects of prior MDMA exposure on sleep, circadian activity, and the circadian pacemaker, and will highlight current gaps in knowledge and suggest areas for future research.

  12. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara


    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA.

  13. The role of peers in the initiation and continuation of ecstasy use.

    Vervaeke, Hylke K E; van Deursen, Lonneke; Korf, Dirk J


    This study is a supplement to the Netherlands XTC Toxicity Study (NeXT), funded by grants from the Netherlands Organisation for Health Research and Development as part of its Addiction Programme. To better understand the processes of peer influence and peer selection, in a field study 106 Ecstasy users (67M/39F, average age 25.4 years) were interviewed face-to-face in Amsterdam in 2005. In the initiation of Ecstasy use, peer influence emerged as the dominating mechanism; peer selection was uncommon. In the continuation of Ecstasy use, peer influence and peer selection occurred reciprocally in a dynamic process, although peer influence made a greater relative contribution. Our study confirms that peer influence is a multidimensional process: influence was quite often reciprocal (with respondents both exerting and undergoing influence) and it could have both restraining and encouraging effects on ecstasy use. The study's limitations are noted.

  14. MDMA Increases Excitability in the Dentate Gyrus: Role of 5HT2A Receptor Induced PGE2 Signaling

    Collins, Stuart A.; Huff, Courtney; Chiaia, Nicolas; Gudelsky, Gary A.; Yamamoto, Bryan K.


    MDMA is a widely abused psychostimulant which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA. Administration of MDMA into the dentate gyrus of rats increased PGE2 concentrations which was prevented by coadministration of MDL100907, a 5HT2A receptor antagonist. MDMA-induced increases in extracellular glutamate were inhibited by local administration of SC-51089, an inhibitor of the EP1 prostaglandin receptor. Systemic administration of SC-51089 during injections of MDMA prevented the decreases in parvalbumin interneurons observed 10 days later. The loss of parvalbumin immunoreactivity after MDMA exposure coincided with a decrease in paired-pulse inhibition and afterdischarge threshold in the dentate gyrus. These changes were prevented by inhibition of EP1 and 5HT2A receptors during MDMA. Additional experiments revealed an increased susceptibility to kainic acid-induced seizures in MDMA treated rats which could be prevented with SC51089 treatments during MDMA exposure. Overall, these findings suggest that 5HT2A receptors mediate MDMA-induced PGE2 signaling and subsequent increases in glutamate. This signaling mediates parvalbumin cell losses as well as physiologic changes in the dentate gyrus, suggesting that the lack of the inhibition provided by these neurons increases the excitability within the dentate gyrus of MDMA treated rats. PMID:26670377

  15. Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors.

    Janelle H P van Wel

    Full Text Available UNLABELLED: MDMA induces positive mood and increases impulse control during intoxication, but only a few studies on the neuropharmacological mechanisms underlying these processes have been conducted. It was hypothesized that pretreatment with 5-HT(1 and 5-HT(2 receptor blockers would prevent MDMA effects on mood and impulsivity. Subjects (N = 17 participated in a double-blind, placebo controlled, within-subject design involving 6 experimental conditions consisting of pretreatment (T1 and treatment (T2. T1 preceded T2 by 30 minutes. T1-T2 combinations were: placebo-placebo, 20 mg pindolol-placebo, 50 mg ketanserin-placebo, placebo-75 mg MDMA, 20 mg pindolol-75 mg MDMA and 50 mg ketanserin-75 g MDMA. Subjects completed a Profile of Mood States (POMS questionnaire and several impulsivity tasks (Stop signal task, Matching familiar figures task, Cue dependent reversal learning task at 1.5 hrs post-treatment. MDMA alone increased both positive (vigor, arousal, friendliness, elation, positive mood and negative affect (anxiety, confusion as assessed by the POMS questionnaire. MDMA also increased stop reaction time in the Stop signal task and reaction time in the Matching familiar figures task. Pretreatment with ketanserin blocked MDMA effects on positive affect, but not negative affect. Ketanserin did not influence the effects of MDMA on impulsivity. Pindolol did not interact with MDMA on any of the measures. In conclusion, 5-HT(2 receptors mediate positive moods induced by MDMA but not negative moods or impulsivity. 5-HT(1 receptors do not appear to be involved in MDMA effects on mood and impulse control. TRIAL REGISTRATION: Nederlands Trial Register NTR2352.

  16. Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes.

    Madry, Milena M; Steuer, Andrea E; Hysek, Cédric M; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas


    Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9-77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-L-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2-2.4 for MDMA and 0.85-0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044-0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable.

  17. Electrophysiological evidence of atypical processing underlying mental set shifting in ecstasy polydrug and polydrug users.

    Roberts, Carl A; Fairclough, Stephen H; McGlone, Francis P; Fisk, John E; Montgomery, Catharine


    Executive functioning deficits are reported in ecstasy users. However research into mental set switching has been equivocal, with behavioral studies suggesting the function is preserved. The current study sought to address the issue of switching deficits in ecstasy users by combining behavioral performance with electrophysiological correlates (electroencephalography; EEG). Twenty ecstasy polydrug users, 20 nonecstasy polydrug users, and 20 drug naive controls were recruited. Participants completed questionnaires about their drug use, sleep quality, fluid intelligence, and current mood state. Each participant completed a mental set switching task (the number-letter task) while EEG measures were recorded. Analysis of variance (ANOVA) revealed no between-group differences on performance of the task; however a regression suggested that ecstasy use was a significant predictor for performance, after controlling for cannabis use. Mixed ANOVA revealed a significant effect of group on the P3, with significant differences between both drug groups and naives. There was also an interaction between electrode and group on the P2 component, with ecstasy users differing from both other groups. On the P3 component the results suggest a reduction in positivity at parieto-occipital electrodes for drug users compared to controls. Furthermore a significant increase in negativity in ecstasy users compared to control groups could be observed in several occipito-parietal electrodes at an N2 component as well as observable atypicalities in early processing (P2) displayed by ecstasy users and polydrug controls. The present study provides evidence of atypical processing of attentional shifting in ecstasy and polydrug users. Deficits in this executive function could reflect cognitive inflexibility and paucity of rapid behavioral adjustment, which may be problematic in real world situations.

  18. Simultaneous polysubstance use among Danish 3,4-methylenedioxymethamphetamine and hallucinogen users

    Licht, Cecilie L; Christoffersen, Maria; Okholm, Mads;


    To describe patterns of simultaneous polysubstance use (SPU) among Danish 3,4-methylenedioxymethamphetamine (MDMA) ("Ecstasy") and hallucinogen users.......To describe patterns of simultaneous polysubstance use (SPU) among Danish 3,4-methylenedioxymethamphetamine (MDMA) ("Ecstasy") and hallucinogen users....


    陈朝阳; 王玉瑾; 景志杰; 宋国华; 庞文彪; 张瑞虎; 郭永昌; 寇冰


    目的:观察3,4-亚甲基二氧基甲基苯丙胺(MDMA)染毒家兔生命体征变化,并对急死与延缓死亡动物体内药物分布进行研究.方法:家兔以10 mgkg-1剂量灌胃(ig)给予MDMA,BL-5生物机能实验系统记录从开始给药到动物被处死前的心电、血压和呼吸等主要生命体征变化;分别于给药2 h和6 h处死动物,采用气-质联用(GC/MS) 法测定组织及体液中MDMA浓度.结果:家兔给药后,四肢出现间歇性震颤,血压升高,呼吸与心率加快,1 h左右达到高峰,之后缓慢下降;给药2 h后体内器官组织中药物浓度高于体液,其中以胃内容、肺及脾含量最高,6 h后组织与血液中药物浓度明显下降,而胆汁与尿液中药物浓度基本不变,胆汁中药物浓度高于其他组织.结论:尿液为鉴定MDMA滥用的最佳检材;对滥用MDMA死亡者脏器组织与体液中药物含量测定,可对用药后急死或延缓死亡做出判断.

  20. Ecstasy research in the 20th century – an introduction

    Nils G. Holm


    Full Text Available Scholars have always been interested in distinctive phenomena in culture and religion. Thus the accounts and achievements of yogis and mystics received attention at an early stage. There is a similar tendency with shamans, different kinds of sorcerers and with the "group-hysterical" phenomena that have appeared from time to time. There is, on the other hand, no major collection of research contributions on all the phenomena belonging to this field. Before proceeding to discuss some of the research produced over this vast area, some of the technical terms and concepts current in this field of study need to be introduced: ecstasy, trance, mysticism, possession, and altered states of consciousness.

  1. Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat.

    Shortall, Sinead E; Macerola, Alice E; Swaby, Rabbi T R; Jayson, Rebecca; Korsah, Chantal; Pillidge, Katharine E; Wigmore, Peter M; Ebling, Francis J P; Richard Green, A; Fone, Kevin C F; King, Madeleine V


    The synthetic cathinone derivative, mephedrone, is a controlled substance across Europe. Its effects have been compared by users to 3,4-methylenedioxymethamphetamine (MDMA), but little data exist on its pharmacological properties. This study compared the behavioural and neurochemical effects of mephedrone with cathinone and MDMA in rats. Young-adult male Lister hooded rats received i.p. cathinone (1 or 4 mg/kg), mephedrone (1, 4 or 10mg/kg) or MDMA (10mg/kg) on two consecutive days weekly for 3 weeks or as a single acute injection (for neurochemical analysis). Locomotor activity (LMA), novel object discrimination (NOD), conditioned emotional response (CER) and prepulse inhibition of the acoustic startle response (PPI) were measured following intermittent drug administration. Dopamine, 5-hydroxytryptamine (5-HT) and their major metabolites were measured in striatum, frontal cortex and hippocampus by high performance liquid chromatography 7 days after intermittent dosing and 2h after acute injection. Cathinone (1, 4 mg/kg), mephedrone (10mg/kg) and MDMA (10mg/kg) induced hyperactivity following the first and sixth injections and sensitization to cathinone and mephedrone occurred with chronic dosing. All drugs impaired NOD and mephedrone (10mg/kg) reduced freezing in response to contextual re-exposure during the CER retention trial. Acute MDMA reduced hippocampal 5-HT and 5-HIAA but the only significant effect on dopamine, 5-HT and their metabolites following chronic dosing was altered hippocampal 3,4-dihydroxyphenylacetic acid (DOPAC), following mephedrone (4, 10mg/kg) and MDMA. At the doses examined, mephedrone, cathinone, and MDMA induced similar effects on behaviour and failed to induce neurotoxic damage when administered intermittently over 3 weeks.

  2. Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

    Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa


    Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

  3. Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain

    Pachmerhiwala, Rashida; Bhide, Nirmal; Straiko, Megan; Gudelsky, Gary A.


    The acute administration of MDMA has been shown to promote glycogenolysis and increase the extracellular concentration of glucose in the striatum. In the present study the role of serotonergic and/or noradrenergic mechanisms in the MDMA-induced increase in extracellular glucose and glycogenolysis was assessed. The relationship of these responses to the hyperthermia produced by MDMA also was examined. The administration of MDMA (10 mg/kg, i.p.) resulted in a significant and sustained increase ...

  4. Two cases of drug eruption caused by MDMA(ecstasy)%苯丙胺类致幻剂引起药疹2例

    夏群力; 罗邦国


    @@ 最近我科诊治了2例因服3,4-亚甲二氧甲基苯丙胺(摇头丸)而引起药疹的患者,现报道如下. 1 临床资料 例1,女,21岁,歌舞厅小姐,因发疹2小时伴有瘙痒,发热38.2℃就诊.皮疹分布于面颈、躯干及四肢,为少量米粒至绿豆大小鲜红色丘疹,部分融合成片状.追问服药史,承认数小时前服用过"摇头丸",以往也多次服用过,从未发过皮疹.

  5. The combined effects of 3,4-methylenedioxymethamphetamine (MDMA) and selected substituted methcathinones on measures of neurotoxicity.

    Miner, Nicholas B; O'Callaghan, James P; Phillips, Tamara J; Janowsky, Aaron


    The rise in popularity of substituted methcathinones (aka "bath salts") has increased the focus on their neurotoxic effects. Two commonly abused methcathinones, 3,4-methylenedioxymethcathinone (methylone, MDMC) and 3,4-methylenedioxypyrovalerone (MDPV), are often concomitantly ingested with the illicit drug 3,4-methylenedioxymethamphetamine (MDMA). To examine potential neurotoxic effects of these drug combinations, C57BL/6J mice were administered 4 i.p. injection of the drugs, at 2h intervals, either singularly: MDMA 15 or 30mg/kg, methylone 20mg/kg, MDPV 1mg/kg; or in combination: methylone/MDMA 20/15mg/kg, MDPV/MDMA 1/15mg/kg. Drug effects on thermoregulation were characterized and striatal tissue analyzed after 2 or 7days for dopamine (DA) and tyrosine hydroxylase (TH) levels, as well as glial fibrillary acidic protein (GFAP) expression. Two days following drug administration, DA and TH were decreased only in the MDMA 30mg/kg group, whereas GFAP expression was dose-dependently increased by MDMA alone. While the combination of the methcathinones with the lower MDMA dose did not affect DA or TH levels, both blocked the MDMA-induced increase in GFAP expression. Seven days following drug administration, there were no significant differences in DA, TH, or GFAP for any treatment group, indicating that changes in DA, TH, and GFAP were transient. Five of the six drug groups exhibited acute hypothermia followed by gradually increasing temperatures. Animals treated with MDPV did not exhibit these biphasic temperature changes, and resembled the saline group. These results indicate that specific effects of both methylone and MDPV on DA depletion or astrocyte activation in the striatum are not additive with effects of MDMA, but block astrogliosis caused by MDMA alone. Additionally, MDPV modulates thermoregulation through a different mechanism than methylone or MDMA. Published by Elsevier Inc.

  6. Ecstasy – a way to religious knowledge: some remarks to Paul Tillich as theologian and philosopher

    Tage Kurtén


    Full Text Available Much of the research examines ecstasy from the point of view of psychology, history or sociology, but a philosophical reflection on ecstasy is missing. Here, some points in the philosophical and theological thinking of Paul Tillich are presented. He can be looked upon as a religious thinker. In this case he is of interest for religiology mainly as historical material. Then he can be seen as a Christian who in modern time has tried theoretically to reflect upon his own religious faith and the place of ecstasy in that faith. He can also be regarded as a philosopher of religion, who tries to reflect universally and critically upon the phenomena of religion and ecstasy. In that case his main contribution to religiology is to help religiology to reflect upon the question of what possible meaning the concept of "religious ecstasy" can have in a modern scientific context. When looking at Tillich's ideas, it is very important to remember that he strives to be both a philosopher of religion and a Christian theologian, and that these two roles are different, according to Tillich. In any analysis of his thinking it is therefore necessary to discriminate between Tillich's philosophical and his theological statement. For Tillich's treatment of revelation and knowledge of revelation there are three central concepts: mystery, ecstasy and miracle. Every revelation has a subjective and an objective side, and they are both necessary for the revelation. Someone must be seized by the manifestation of the mystery and something must occur through which the mystery of revelation seizes someone, says Tillich. The subjective side is called ecstasy, the objective miracle.

  7. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)


    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  8. The effects of multitasking on psychological stress reactivity in recreational users of cannabis and MDMA.

    Wetherell, Mark A; Atherton, Katie; Grainger, Jessica; Brosnan, Robert; Scholey, Andrew B


    Cannabis and 3,4-methylenedioxymethamphetamine (MDMA) use is associated with psychobiological and neurocognitive deficits. Assessments of the latter typically include tests of memory and everyday cognitive functioning. However, to date, little attention has been paid to effects of drug use on psychological stress reactivity. We report three studies examining the effects of recreational use of cannabis and MDMA on mood and psychological responses to multitasking using a cognitively demanding laboratory stressor that provides an analogue for everyday situations involving responses to multiple stimuli. The effects of the multitasking framework on mood and perceived workload were assessed in cannabis (N=25), younger (N=18) and older (N=20) MDMA users and compared with non-target drug controls. Compared with respective control groups, cannabis users became less alert and content, and both MDMA groups became less calm following acute stress. Unexpectedly, the stressor increased ratings of calm in cannabis users. Users also scored higher than their controls with respect to ratings of resources needed to complete the multitasking framework. These findings show, for the first time, that recreational use of cannabis and MDMA, beyond the period of intoxication, can negatively influence psychological responses to a multitasking stressor, and this may have implications for real-life situations which place high demands on cognitive resources. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions

    Rietjens, S.J.; Hondebrink, L.; Westerink, R.H.S.; Meulenbelt, J.


    Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates t

  10. Gender differences in hyperthermia and regional 5-HT and 5-HIAA depletion in the brain following MDMA administration in rats

    Wallinga, Alinde E.; Grahlmann, Carolin; Granneman, Ramon A.; Koolhaas, Jaap M.; Buwalda, Bauke


    In the present research the role of gender in MDMA-induced hyperthermia and serotonin depletion is studied by injecting male and female male rats with MDMA or saline 3 times (i.p.) with 3 h interval at dosages of 0.3, 1, 3 or 9 mg/kg at an ambient temperature of 25 degrees C. The acute hyperthermia

  11. Say "No"to Ecstasy--Ecstasy Use Triggers Deep Depression%拒绝毒品--服用摇头丸,引发抑郁症

    Jo Revill; 王启国


    @@ Just two tablets enough to cause long-term health problems, psychologists ( 心理学家 ) are told Ecstasy ( 摇头丸), the so-called(所谓的) love drug taken by hundreds of thousands each weekend, can result in crippling depression after just a couple of tablets, a study revealed.

  12. The effect of Ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT) gene

    T. Schilt; M.W.J. Koeter; M.M.L. de Win; J.R. Zinkstok; T.A. van Amelsvoort; B. Schmand; W. van den Brink


    There is ample evidence for decreased verbal memory in heavy Ecstasy users. However, findings on the presence of a dose-response relation are inconsistent, possibly due to individual differences in genetic vulnerability. Catechol-O-methyltransferase (COMT) is involved in the catabolism of Ecstasy. T

  13. The Students\\' Knowledge, Attitude and Performance about Prevention of Using of Ecstasy

    Mitra Zolfaghari


    Full Text Available Introduction: In recent decades because of stimulant and hallucinogenic properties of ecstasy, it has been found so many users among adolescent and youth people. The aim of present study was the study of students' knowledge, attitude and performance related to prevention of using of ecstasy. Method: This descriptive – analytic study has done in 400 female students of government schools of zone no. 17. The sample selected by clustering random sampling and their knowledge, attitude, and performance measured by using of researchers developed questionnaire which shown sufficient level of validity and reliability. Results: The results showed that the majority of students (41% had low knowledge, 56% had positive attitude, and 55.1% had good performance related to prevention of using of ecstasy. Also, there was positive relationship between students' knowledge and attitude also attitude and performance. There was also positive relationship between some of the demographic characteristics and the students' knowledge, attitude and performance related to prevention of using of ecstasy. Conclusion: Finding of the research showed that the students' knowledge related to use of ecstasy is low, therefore appropriate instructional intervention in order to promote the students' knowledge is necessary.

  14. The P3 in 'ecstasy' polydrug users during response inhibition and execution.

    Gamma, Alex; Brandeis, Daniel; Brandeis, Ruven; Vollenweider, Franz X


    Substance abuse and associated externalizing disorders are characterized by behavioural disinhibition and low impulse control, with reduced neural inhibition postulated to be the common underlying brain mechanism. The P3 component of event-related potentials (ERPs) is a widely used neurophysiological measure thought to reflect inhibitory brain processes, but as yet has not been assessed in ecstasy users. We recorded ERPs evoked by a Continuous Performance Test (CPT) in 16 current ecstasy polydrug users and 17 controls. The CPT included conditions where a prepared motor response had to be executed (Go) or inhibited (NoGo). Both controls and ecstasy users showed normal, robust patterns of P3 anteriorization and delay in the NoGo compared to the Go condition. Ecstasy users had lower P3 amplitudes at midline electrodes and a less anterior location of NoGo P3 peaks. These effects became weaker after statistically controlling for age, educational level and lifetime cannabis use. While lower P3 amplitudes are consistent with higher levels of neural disinhibition in ecstasy polydrug users, the normal switch pattern between response execution and inhibition, and the less anterior location of the NoGo P3, do not indicate disturbed inhibitory brain mechanisms.

  15. Psychological Distress and Drug Use Patterns of Young Adult Ecstasy Users: A Complementary Analysis of Australian Datasets.

    Smirnov, Andrew; Hayatbakhsh, Reza; Alati, Rosa; Legosz, Margot; Burns, Lucy; Kemp, Robert; Wells, Helene; Najman, Jake M


    We examine psychological distress (PD) in young adult Ecstasy users in relation to age of initiation and frequency of use of Ecstasy, cannabis, alcohol, and tobacco. Using two Australian community samples, we assess whether different sampling methods produce comparable estimates of these associations. The Natural History Study of Drug Use (NHSDU; N = 339) in 2009 used population sampling and the 2009 Ecstasy and Related Drug Reporting System (EDRS; N = 359) used purposive sampling. Participants, aged 19-23 years, were recurrent Ecstasy users. PD was assessed using Kessler 10 in the EDRS and Hospital Anxiety Depression Scale in the NHSDU. In both samples, PD was associated with daily tobacco use and early drug initiation, but not frequent Ecstasy use. One-third smoke tobacco daily. Study limitations and implications are noted.

  16. On Weak Regular *-semigroups

    Yong Hua LI; Hai Bin KAN; Bing Jun YU


    In this paper, a special kind of partial algebras called projective partial groupoids is defined.It is proved that the inverse image of all projections of a fundamental weak regular *-semigroup under the homomorphism induced by the maximum idempotent-separating congruence of a weak regular *-semigroup has a projective partial groupoid structure. Moreover, a weak regular *-product which connects a fundamental weak regular *-semigroup with corresponding projective partial groupoid is defined and characterized. It is finally proved that every weak regular *-product is in fact a weak regular *-semigroup and any weak regular *-semigroup is constructed in this way.

  17. Ecstasy intoxication as an unusual cause of epileptic seizures in young children.

    Pauwels, Steven; Lemmens, Francis; Eerdekens, Kim; Penders, Joris; Poesen, Koen; Desmet, Koen; Vermeersch, Pieter


    In light of the widespread use of ecstasy, it is surprising that only few cases of intoxicated young children have been reported. Patients almost invariably present with convulsions accompanied by sympathetic signs and symptoms such as hyperthermia. Two new cases of toddlers intoxicated with ecstasy are described. The first patient, a 19-month-old boy, presented with convulsions but no sympathetic signs. The pediatrician's suspicion was raised because of the absence of a postictal state. The second patient, a 20-month-old girl, had a more typical presentation with convulsions and hyperthermia. Her story illustrates the fact that immunoassays for toxicological screening can easily miss traces of additional illicit drugs present in the urine such as cocaine. The presence of other illicit drugs provides clues to the child's risky environment and should lead to further investigation. Finally, we review the available literature on ecstasy intoxication to summarize the key presenting manifestations.

  18. Developing the climate schools: ecstasy module--a universal Internet-based drug prevention program.

    Newton, Nicola C; Teesson, Maree; Newton, Kathyrn L


    The Climate Schools: Ecstasy module is a universal harm-minimisation school-based prevention program for adolescents aged 14 to 16 years. The program was developed to address the need for Ecstasy prevention given the increasing use of Ecstasy use among young Australians. The core content of the program is delivered over the Internet using cartoon storylines to engage students, and the teacher-driven activities reinforce the core information. The three-lesson program is embedded within the school health curriculum and is easy to implement with minimal teacher training required. The program was developed in 2010 through extensive collaboration with students (n = 8), teachers (n = 10) and health professionals (n = 10) in Sydney, Australia. This article describes the formative research and process of planning that formed the development of the program and the evidence base underpinning the approach.

  19. Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain.

    Pachmerhiwala, Rashida; Bhide, Nirmal; Straiko, Megan; Gudelsky, Gary A


    The acute administration of MDMA has been shown to promote glycogenolysis and increase the extracellular concentration of glucose in the striatum. In the present study the role of serotonergic and/or noradrenergic mechanisms in the MDMA-induced increase in extracellular glucose and glycogenolysis was assessed. The relationship of these responses to the hyperthermia produced by MDMA also was examined. The administration of MDMA (10mg/kg, i.p.) resulted in a significant and sustained increase of 65-100% in the extracellular concentration of glucose in the striatum, as well as in the prefrontal cortex and hippocampus, and a 35% decrease in brain glycogen content. Peripheral blood glucose was modestly increased by 32% after MDMA treatment. Treatment of rats with fluoxetine (10mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose in the striatum but had no effect on MDMA-induced glycogenolysis or hyperthermia. Treatment with prazosin (1mg/kg, i.p.) did not alter the glucose or glycogen responses to MDMA but completely suppressed MDMA-induced hyperthermia. Finally, propranolol (3mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose and glycogenolysis but did not alter MDMA-induced hyperthermia. The present results suggest that MDMA increases extracellular glucose in multiple brain regions, and that this response involves both serotonergic and noradrenergic mechanisms. Furthermore, beta-adrenergic and alpha-adrenergic receptors appear to contribute to MDMA-induced glycogenolysis and hyperthermia, respectively. Finally, hyperthermia, glycogenolysis and elevated extracellular glucose appear to be independent, unrelated responses to acute MDMA administration.

  20. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A


    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures.

  1. Drug intelligence based on MDMA tablets data: 2. Physical characteristics profiling.

    Marquis, Raymond; Weyermann, Céline; Delaporte, Céline; Esseiva, Pierre; Aalberg, Laura; Besacier, Fabrice; Bozenko, Joseph S; Dahlenburg, Rainer; Kopper, Carola; Zrcek, Frantisek


    One of the tasks of the European project entitled "Collaborative Harmonisation of Methods for Profiling of Amphetamine Type Stimulants" (CHAMP) funded by the sixth framework programme of the European Commission was to develop a harmonised methodology for MDMA profiling and the creation of a common database in a drug intelligence perspective. Part I was dedicated to the analysis of organic impurities formed during synthesis in order to investigate traffic tendencies and highlight potential links between samples, whereas this part focuses on physical characteristics of the MDMA tablets. Diameter, thickness, weight and score were demonstrated to be reliable and relevant features in this drug intelligence perspective. Distributions of samples coming from the same post-tabletting batch (post-TB) and samples coming from different post-TB were very well discriminated by using the squared Euclidean or the Manhattan distance on standardised data. Our findings demonstrated the possibility to discriminate between MDMA samples issued from different post-TB and to find out links between samples coming from a same post-TB. Furthermore, the hypothesis that most of the MDMA samples found on the international market come from the same countries was supported.




    It is proved that for a left Noetherian z-graded ring A,if every finitely generated graded A-module has finite projective dimension(i.e-,A is gr-regular)then every finitely generated A-module has finite projective dimension(i.e.,A is regular).Some applications of this result to filtered rings and some classical cases are also given.

  3. Some psycho-physiological aspects of ecstasy in recent research

    Nora Ahlberg


    Full Text Available The intention of this article is to present some psycho-physiological perspectives of recent date concerned with the phenomenon of ecstasy. As almost none of this research has yet been assimilated by comparative religion, the focus here is on illustrating some of the background for renewed speculation on the relationship between psyche and soma. Traditional Western science has usually operated with a distinction between external and internal processes. Perhaps owing to this idea of the independence of our internal processes from our intentional consciousness, reports from other cultures such as those concerning the extraordinary achievements of holy men (e.g. their capacity to lie buried for days, or survive unclothed at very low temperatures have tended to be ignored as fantastic rumours (which, to some extent, is certainly true and myths. In a similar way the varieties of religious ecstatic states have often been countered with a shrug by psychiatrists. The recently renewed interest in consciousness within general psychology, together with what may be called marginal psychology and the drug revolt of youth culture have, however, provoked new speculation concerning human potential, speculation which in due time might also benefit comparative religion. From the perspective of comparative religion the primary concern is with cultural tradition and interpretation. Among our many new potential methods for better understanding ecstatic phenomena by means of experimental methods, biofeedback has been the most sensational one. It is above all the research in biofeedback that has forced many scientists to reconsider their view of the autonomic nervous system as a system completely independent of human will and control.

  4. "The Great Unmentionable": Exploring the Pleasures and Benefits of Ecstasy from the Perspectives of Drug Users

    Hunt, Geoffrey P.; Evans, Kristin


    Although legal and illegal drugs have throughout history given pleasure to those who consume them, research in the drug field has ignored this central and fundamental feature. The absence of any discussion of pleasure is striking when one considers the contemporary literature on ecstasy and the dance scene. Pleasure is still missing within much of…

  5. Ecstasy Use and Suicidal Behavior among Adolescents: Findings from a National Survey

    Kim, Jueun; Fan, Bin; Liu, Xinhua; Kerner, Nancy; Wu, Ping


    The relationship between ecstasy use and suicidal behavior among adolescents in the United States was examined. Data from the adolescent subsample (ages 12-17, N = 19,301) of the 2000 National Household Survey on Drug Abuse were used in the analyses. Information on adolescent substance use, suicidal behaviors, and related sociodemographic, family,…

  6. Application of the Theory of Reason Action for Preventing of Ecstasy Abuse among College Students

    Majid Barati


    Full Text Available Introduction: The aim of the present study was assessed the effect of educational program for preventing of ecstasy abuse among college students in Hamadan based on Theory of Reason Action (TRA. Method: A quasi-experimental study carried out in college students. A total number of 140 students were selected through randomized cluster sampling and randomly assigned to the intervention (n=70 and the control (n=70 groups. Data-gathering tools consisted of a two-part questionnaire: Knowledge of ecstasy abuse consequences and one scale for measuring TRA variables. Respondents in the control and experimental groups completed questionnaires at before and two months after intervention. Results: The results showed that among constructs of the theory of reason action, subjective norms were better predictor of ecstasy abuse. There were significant differences between the scores of reason action constructs namely: attitude against drug abuse, subjective norms and intention of ecstasy abuse with consideration of group (witness and experimental. Conclusion: With regard to the results of the current study, special education based on Theory of Reasoned Action is effective in improving of attitude, subjective norm and behavioral intention of students. Therefore it is highly recommended that TRA education can be use for preventing of drug abuse education programs.

  7. "The Great Unmentionable": Exploring the Pleasures and Benefits of Ecstasy from the Perspectives of Drug Users

    Hunt, Geoffrey P.; Evans, Kristin


    Although legal and illegal drugs have throughout history given pleasure to those who consume them, research in the drug field has ignored this central and fundamental feature. The absence of any discussion of pleasure is striking when one considers the contemporary literature on ecstasy and the dance scene. Pleasure is still missing within much of…

  8. The role of peers in the initiation and continuation of ecstasy use

    Vervaeke, H.K.E.; van Deursen, L.; Korf, D.J.


    This study is a supplement to the Netherlands XTC Toxicity Study (NeXT), funded by grants from the Netherlands Organisation for Health Research and Development as part of its Addiction Programme. To better understand the processes of peer influence and peer selection, in a field study 106 Ecstasy us

  9. Self-esteem and HIV risk practices among young adult ecstasy users.

    Klein, Hugh; Elifson, Kirk W; Sterk, Claire E


    This study examines the role that self-esteem plays in HIV-related risk taking among users of the drug, Ecstasy. The first part of the analysis focuses on the relationship of self-esteem to HIV risk-taking. The second part examines predictors of self-esteem in this population. Conducted between 2002 and 2004, the research is based on a sample of 283 young adult Ecstasy users who completed approximately two-hour-long, face-to-face interviews via computer-assisted structured interviews. Study participants were recruited in the Atlanta, Georgia metropolitan area using targeted sampling and ethnographic mapping. Results indicated that self-esteem is associated with a variety of risky practices, including: the number of sex partners that people had, individuals' likelihood of having multiple sex partners, the number of different illegal drugs people used, and their condom use self-efficacy. The multivariate analysis conducted to ascertain the factors that impact participants' levels of self-esteem yielded six factors: educational attainment (positive), coming from a family-of-origin whose members got along well (positive), the extent of alcohol problems (negative), the number of positive effects experienced as a result of Ecstasy use (positive), the number of negative effects experienced as a result of Ecstasy use (negative), and the extent of experiencing symptoms of post-traumatic stress disorder (negative).

  10. Initiation and continuation : social context and behavioural aspects of ecstasy use

    H.K.E. Vervaeke


    Drug law enforcement does not have the deterrent effects on the use of ecstasy that are intended by international anti-drugs agreements or national legislation. In addition, prevention programs generally fail to reduce substance use. With regard to drug use, Dutch policy can be characterised as harm

  11. Regular Expression Pocket Reference

    Stubblebine, Tony


    This handy little book offers programmers a complete overview of the syntax and semantics of regular expressions that are at the heart of every text-processing application. Ideal as a quick reference, Regular Expression Pocket Reference covers the regular expression APIs for Perl 5.8, Ruby (including some upcoming 1.9 features), Java, PHP, .NET and C#, Python, vi, JavaScript, and the PCRE regular expression libraries. This concise and easy-to-use reference puts a very powerful tool for manipulating text and data right at your fingertips. Composed of a mixture of symbols and text, regular exp

  12. Dimensional regularization is generic

    Fujikawa, Kazuo


    The absence of the quadratic divergence in the Higgs sector of the Standard Model in the dimensional regularization is usually regarded to be an exceptional property of a specific regularization. To understand what is going on in the dimensional regularization, we illustrate how to reproduce the results of the dimensional regularization for the $\\lambda\\phi^{4}$ theory in the more conventional regularization such as the higher derivative regularization; the basic postulate involved is that the quadratically divergent induced mass, which is independent of the scale change of the physical mass, is kinematical and unphysical. This is consistent with the derivation of the Callan-Symanzik equation, which is a comparison of two theories with slightly different masses, for the $\\lambda\\phi^{4}$ theory without encountering the quadratic divergence. We thus suggest that the dimensional regularization is generic in a bottom-up approach starting with a successful low-energy theory. We also define a modified version of t...

  13. 3,4-Methylenedioxymethamphetamine (MDMA) Abuse Markedly Inhibits Acetylcholinesterase Activity and Induces Severe Oxidative Damage and Liperoxidative Damage


    Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers. Methods 120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods. Results Compared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P<0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P<0.0001). The Pearson product-moment correlation analysis between the values of AChE and biochemical parameters in 120 MDMA abusers showed that significant linear negative correlation was present between the activity of AChE and the levels of LPO in plasma and erythrocytes (P<0.0005-0.0001), while significant linear positive correlation was observed between the activity of AchE and the activities of SOD, CAT and GPX (P<0.0001). The reliability analysis for the above biochemical parameters reflecting oxidative and lipoperoxidative damages in MDMA abusers suggested that the reliability coefficient (alpha) was 0.8124, and that the standardized item alpha was 0.9453. Conclusion The findings in the present study suggest that MDMA abuse can induce another neurotoxicity that significantly inhibits acetylcholinesterase activity and aggravates a series of free radical chain reactions and oxidative stress in the bodies of MDMA abusers, thereby resulting in severe neural, oxidative and lipoperoxidative damages in MDMA abusers.

  14. Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis.

    Sébastien Ballesta

    Full Text Available 3,4-methylenedioxy-N-methyl amphetamine (MDMA is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play. In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors.

  15. Learning, Memory, and Executive Function in New MDMA Users: A Two-Year Follow-up Study

    Daniel eWagner


    Full Text Available 3,4-Methylenedioxymethamphetamine (MDMA is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a two-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. 96 subjects were assessed at the second follow-up assessment: 31 of these were non-users, 55 moderate-users and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns and subjective well-being were assessed.The Repeated measures analysis of variance (rANOVA revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of two years. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, in the recent study, further deterioration in continuing MDMA-users was not observed.

  16. Robust Sparse Analysis Regularization

    Vaiter, Samuel; Dossal, Charles; Fadili, Jalal


    This paper studies the properties of L1-analysis regularization for the resolution of linear inverse problems. Most previous works consider sparse synthesis priors where the sparsity is measured as the L1 norm of the coefficients that synthesize the signal in a given dictionary. In contrast, the more general analysis regularization minimizes the L1 norm of the correlations between the signal and the atoms in the dictionary. The corresponding variational problem includes several well-known regularizations such as the discrete total variation and the fused lasso. We first prove that a solution of analysis regularization is a piecewise affine function of the observations. Similarly, it is a piecewise affine function of the regularization parameter. This allows us to compute the degrees of freedom associated to sparse analysis estimators. Another contribution gives a sufficient condition to ensure that a signal is the unique solution of the analysis regularization when there is no noise in the observations. The s...

  17. Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

    Ma, Kuo-Hsing; Liu, Tsung-Ta; Weng, Shao-Ju; Chen, Chien-Fu F.; Huang, Yuahn-Sieh; Chueh, Sheau-Huei; Liao, Mei-Hsiu; Chang, Kang-Wei; Sung, Chi-Chang; Hsu, Te-Hung; Huang, Wen-Sheng; Cheng, Cheng-Yi


    3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate. PMID:27941910

  18. The association between the negative effects attributed to ecstasy use and measures of cognition and mood among users.

    Fisk, John E; Montgomery, Catharine; Murphy, Philip N


    In self reports, abstinent ecstasy/polydrug users claim that they experience certain ongoing affective and psychological changes including elevated anxiety, arousal, and depression. In addition, various aspects of cognition (e.g., everyday memory, reasoning, executive functioning) appear to be affected. The present paper investigated the link between these two psychological sequelae. Ninety-five ecstasy/polydrug users completed tests of reasoning, intelligence, information processing speed, executive functioning, and everyday memory. Affect was measured via a mood adjective checklist. Adverse effects attributed to ecstasy were measured via responses to adjectives reflecting changes in users since they started using the drug. In addition, indicators of sleep quality and daytime sleepiness were obtained. Users attributed a number of adverse effects to ecstasy, namely heightened irritability, depression, paranoia, and deteriorating health. Adverse effects were significantly and negatively correlated with aspects of intelligence, everyday memory, and sleep quality. Length of use of ecstasy use was positively correlated with adverse effects. While many users attribute a number of adverse affects to their use of ecstasy, it remains unclear whether these self-perceptions are a corollary of the psychopharmacological effects of the drug or reflect factors which in fact predate its use.

  19. Regular expressions cookbook

    Goyvaerts, Jan


    This cookbook provides more than 100 recipes to help you crunch data and manipulate text with regular expressions. Every programmer can find uses for regular expressions, but their power doesn't come worry-free. Even seasoned users often suffer from poor performance, false positives, false negatives, or perplexing bugs. Regular Expressions Cookbook offers step-by-step instructions for some of the most common tasks involving this tool, with recipes for C#, Java, JavaScript, Perl, PHP, Python, Ruby, and VB.NET. With this book, you will: Understand the basics of regular expressions through a

  20. Regularization in kernel learning

    Mendelson, Shahar; 10.1214/09-AOS728


    Under mild assumptions on the kernel, we obtain the best known error rates in a regularized learning scenario taking place in the corresponding reproducing kernel Hilbert space (RKHS). The main novelty in the analysis is a proof that one can use a regularization term that grows significantly slower than the standard quadratic growth in the RKHS norm.

  1. Regular database update logics

    Spruit, Paul; Wieringa, Roel; Meyer, John-Jules


    We study regular first-order update logic (FUL), which is a variant of regular dynamic logic in which updates to function symbols as well as to predicate symbols are possible. We fi1rst study FUL without making assumptions about atomic updates. Second, we look at relational algebra update logic (RAU

  2. Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

    Vivian Capilla-Gonzalez


    Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

  3. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Rafael eDe La Torre


    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  4. Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice

    Johansson, Emily M.; García-Gutiérrez, María S.; Moscoso-Castro, María; Manzanares, Jorge; Valverde, Olga


    The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. PMID:26566284

  5. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

    Vidal-Infer Antonio


    Full Text Available Abstract Background Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA is often combined with ethanol (EtOH. The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze. Methods Adolescent OF1 mice were exposed to EtOH (1.25 g/kg on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42. MDMA (10 or 20 mg/kg was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42, resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured. Results At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin. Conclusions The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood.

  6. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

    O'Shea Esther


    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

  7. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA): regulation by CB2 receptors and implications for neurotoxicity


    Background 3,4-Methylenedioxymethamphetamine (MDMA) produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β) and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra) levels and IL-1 receptor type I (IL-1RI) expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI) and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p.) and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p.) was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v.) was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity. PMID:21595923

  8. Regularization by External Variables

    Bossolini, Elena; Edwards, R.; Glendinning, P. A.


    Regularization was a big topic at the 2016 CRM Intensive Research Program on Advances in Nonsmooth Dynamics. There are many open questions concerning well known kinds of regularization (e.g., by smoothing or hysteresis). Here, we propose a framework for an alternative and important kind of regula...... of regularization, by external variables that shadow either the state or the switch of the original system. The shadow systems are derived from and inspired by various applications in electronic control, predator-prey preference, time delay, and genetic regulation....

  9. Differential experiences of the psychobiological sequelae of ecstasy use: quantitative and qualitative data from an internet study.

    Rodgers, Jacqui; Buchanan, Tom; Pearson, Carol; Parrott, Andy C; Ling, J; Hefferman, T M; Scholey, A B


    Previous work provided preliminary evidence that different patterns of use among ecstasy users may impact on perceived side-effects. Participants recruited via an ecstasy-related bulletin board differed in their responses compared to those recruited via other means. The present investigation compares self-reports of psychobiological difficulties among ecstasy users recruited either via a bulletin board or by alternative methods. Qualitative data included reports of any negative or positive changes attributable to ecstasy use and reasons for cessation of use. An Internet-based design was utilized and 209 volunteers completed the study, 117 of whom were recruited via a bulletin board devoted to discussion of ecstasy. Psychobiological difficulties attributable to ecstasy use varied, with mood fluctuation the most common. Differences between the two groups in the extent to which these problems were reported was found. Bulletin board recruits were less likely to report anxiety or poor concentration, but more likely to report tremors/twitches. For the whole sample, lifetime use was associated more with psychobiologial problems, although this pattern was stronger and more pervasive for the non-bulletin board participants. Bulletin board recruits were more aware of possible negative psychological effects and were more likely to report adopting harm reduction strategies. From the qualitative data three negative consequences of use were identified, the most common of which was "psychological problems". In support of the quantitative findings the likelihood of reporting psychological problems increased with lifetime exposure to ecstasy in both recruitment conditions but interestingly this did not appear to impact on reasons for cessation of use. Participants also reported a number of effects that they regarded as beneficial. Future research should also take these aspects of use into account.

  10. Regularized maximum correntropy machine

    Wang, Jim Jing-Yan


    In this paper we investigate the usage of regularized correntropy framework for learning of classifiers from noisy labels. The class label predictors learned by minimizing transitional loss functions are sensitive to the noisy and outlying labels of training samples, because the transitional loss functions are equally applied to all the samples. To solve this problem, we propose to learn the class label predictors by maximizing the correntropy between the predicted labels and the true labels of the training samples, under the regularized Maximum Correntropy Criteria (MCC) framework. Moreover, we regularize the predictor parameter to control the complexity of the predictor. The learning problem is formulated by an objective function considering the parameter regularization and MCC simultaneously. By optimizing the objective function alternately, we develop a novel predictor learning algorithm. The experiments on two challenging pattern classification tasks show that it significantly outperforms the machines with transitional loss functions.

  11. Regular Expression Containment

    Henglein, Fritz; Nielsen, Lasse


    We present a new sound and complete axiomatization of regular expression containment. It consists of the conventional axiomatiza- tion of concatenation, alternation, empty set and (the singleton set containing) the empty string as an idempotent semiring, the fixed- point rule E* = 1 + E × E......* for Kleene-star, and a general coin- duction rule as the only additional rule. Our axiomatization gives rise to a natural computational inter- pretation of regular expressions as simple types that represent parse trees, and of containment proofs as coercions. This gives the axiom- atization a Curry......-Howard-style constructive interpretation: Con- tainment proofs do not only certify a language-theoretic contain- ment, but, under our computational interpretation, constructively transform a membership proof of a string in one regular expres- sion into a membership proof of the same string in another regular expression. We...

  12. Regularities of Multifractal Measures

    Hun Ki Baek


    First, we prove the decomposition theorem for the regularities of multifractal Hausdorff measure and packing measure in $\\mathbb{R}^d$. This decomposition theorem enables us to split a set into regular and irregular parts, so that we can analyze each separately, and recombine them without affecting density properties. Next, we give some properties related to multifractal Hausdorff and packing densities. Finally, we extend the density theorem in [6] to any measurable set.

  13. On Regular Linear Relations

    T. (A)LVAREZ


    For a closed linear relation in a Banach space the concept of regularity is introduced and studied.It is shown that many of the results of Mbekhta and other authors for operators remain valid in the context of multivalued linear operators.We also extend the punctured neighbourhood theorem for operators to linear relations and as an application we obtain a characterization of semiFredholm linear relations which are regular.

  14. MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.

    Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K


    MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Methyl 3-[3',4'-(methylenedioxy)phenyl]-2-methyl glycidate: an ecstasy precursor seized in Sydney, Australia.

    Collins, Michael; Heagney, Aaron; Cordaro, Frank; Odgers, David; Tarrant, Gregory; Stewart, Samantha


    Five 44 gallon drums labeled as glycidyl methacrylate were seized by the Australian Customs Service and the Australian Federal Police at Port Botany, Sydney, Australia, in December 2004. Each drum contained a white, semisolid substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine (MDMA). Gas chromatography-mass spectroscopy (GC/MS) analysis demonstrated that the material was neither glycidyl methacrylate nor MDMA. Because intelligence sources employed by federal agents indicated that this material was in some way connected to MDMA production, suspicion fell on the various MDMA precursor chemicals. Using a number of techniques including proton nuclear magnetic resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown substance was eventually identified as methyl 3-[3',4'(methylenedioxy)phenyl]-2-methyl glycidate. The substance was also subjected to a published hydrolysis and decarboxylation procedure and gave a high yield of the MDMA precursor chemical, 3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a "precursor to a precursor."

  16. New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain.

    Ibrahim M Shokry

    Full Text Available In spite of the fact that systemic administration of MDMA elicits serotonin syndrome, direct intracranial administration fails to reproduce the effect. To reconcile these findings, it has been suggested that the cause of serotonin syndrome is attributed mainly to MDMA hepatic metabolites, and less likely to MDMA itself. Recently, however, this explanation has been challenged, and alternative hypotheses need to be explored. Here, we tested the hypothesis that serotonin syndrome is the result of excessive 5HT simultaneously in many brain areas, while MDMA administered intracranially fails to cause serotonin syndrome because it produces only a localized effect at the delivery site and not to other parts of the brain. This hypothesis was examined using adult male Sprague Dawley rats by comparing 5HT responses in the right and left hemispheric frontal cortices, right and left hemispheric diencephalons, and medullar raphe nucleus. Occurrence of serotonin syndrome was confirmed by measuring change in body temperature. Administration routes included intraperitoneal (IP, intracerebroventricular (ICV and reverse microdialysis. First, we found that IP administration caused excessive 5HT in all five sites investigated and induced hypothermia, suggesting the development of the serotonin syndrome. In contrast, ICV and reverse microdialysis caused excessive 5HT only in regions of delivery sites without changes in body-core temperature, suggesting the absence of the syndrome. Next, chemical dyes were used to trace differences in distribution and diffusion patterns between administration routes. After systemic administration, the dyes were found to be evenly distributed in the brain. However, the dyes administered through ICV or reverse microdialysis injection still remained in the delivery sites, poorly diffusing to the brain. In conclusion, intracranial MDMA administration in one area has no or little effect on other areas, which must be considered a plausible

  17. Regularized Structural Equation Modeling.

    Jacobucci, Ross; Grimm, Kevin J; McArdle, John J

    A new method is proposed that extends the use of regularization in both lasso and ridge regression to structural equation models. The method is termed regularized structural equation modeling (RegSEM). RegSEM penalizes specific parameters in structural equation models, with the goal of creating easier to understand and simpler models. Although regularization has gained wide adoption in regression, very little has transferred to models with latent variables. By adding penalties to specific parameters in a structural equation model, researchers have a high level of flexibility in reducing model complexity, overcoming poor fitting models, and the creation of models that are more likely to generalize to new samples. The proposed method was evaluated through a simulation study, two illustrative examples involving a measurement model, and one empirical example involving the structural part of the model to demonstrate RegSEM's utility.

  18. Regularity of Bound States

    Faupin, Jeremy; Møller, Jacob Schach; Skibsted, Erik


    We study regularity of bound states pertaining to embedded eigenvalues of a self-adjoint operator H, with respect to an auxiliary operator A that is conjugate to H in the sense of Mourre. We work within the framework of singular Mourre theory which enables us to deal with confined massless Pauli–......–Fierz models, our primary example, and many-body AC-Stark Hamiltonians. In the simpler context of regular Mourre theory, our results boil down to an improvement of results obtained recently in [8, 9]....

  19. Manifold Regularized Reinforcement Learning.

    Li, Hongliang; Liu, Derong; Wang, Ding


    This paper introduces a novel manifold regularized reinforcement learning scheme for continuous Markov decision processes. Smooth feature representations for value function approximation can be automatically learned using the unsupervised manifold regularization method. The learned features are data-driven, and can be adapted to the geometry of the state space. Furthermore, the scheme provides a direct basis representation extension for novel samples during policy learning and control. The performance of the proposed scheme is evaluated on two benchmark control tasks, i.e., the inverted pendulum and the energy storage problem. Simulation results illustrate the concepts of the proposed scheme and show that it can obtain excellent performance.

  20. Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.

    Francis, Sunday M; Kirkpatrick, Matthew G; de Wit, Harriet; Jacob, Suma


    The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of

  1. Intravenous self-administration of mephedrone, methylone and MDMA in female rats.

    Creehan, Kevin M; Vandewater, Sophia A; Taffe, Michael A


    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation.

  2. Annotation of Regular Polysemy

    Martinez Alonso, Hector

    Regular polysemy has received a lot of attention from the theory of lexical semantics and from computational linguistics. However, there is no consensus on how to represent the sense of underspecified examples at the token level, namely when annotating or disambiguating senses of metonymic words...

  3. [AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders].

    Thomasius, R; Gouzoulis-Mayfrank, E; Karus, C; Wiedenmann, H; Hermle, L; Sack, P M; Zeichner, D; Küstner, U; Schindler, A; Krüger, A; Uhlmann, S; Petersen, K U; Zapletalova, P; Wartberg, L; Schütz, C G; Schulte-Markwort, M; Obrocki, J; Heinz, A; Schmoldt, A


    Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen-related disorders is introduced.

  4. Pigment Identification on "The Ecstasy of St. Theresa" Painting by Raman Microscopy

    Marano, D.; Marmontelli, M.; De Benedetto, G. E.; Catalano, I. M.; Sabbatini, L.; Vona, F.

    A study of the pigments of "The Ecstasy of St. Theresa," a seventeenth century oil painting on canvas, was performed by Raman microscopy. Lazurite was identified in both Jesus Christ's and St. Theresa's mantles as the pigment responsible for the blue coloration. Litharge was identified inside the black bitumen layer. Usually the bitumen needed a lot of time to dry in the air when mixed with drying oil. Litharge was used by the artist to decrease the oil drying time. A complementary study, using micro-Raman and SEM, allowed us to identify red ochre as the pigment responsible for the red coloration in the altar on the left side of the painting.

  5. Sparse structure regularized ranking

    Wang, Jim Jing-Yan


    Learning ranking scores is critical for the multimedia database retrieval problem. In this paper, we propose a novel ranking score learning algorithm by exploring the sparse structure and using it to regularize ranking scores. To explore the sparse structure, we assume that each multimedia object could be represented as a sparse linear combination of all other objects, and combination coefficients are regarded as a similarity measure between objects and used to regularize their ranking scores. Moreover, we propose to learn the sparse combination coefficients and the ranking scores simultaneously. A unified objective function is constructed with regard to both the combination coefficients and the ranking scores, and is optimized by an iterative algorithm. Experiments on two multimedia database retrieval data sets demonstrate the significant improvements of the propose algorithm over state-of-the-art ranking score learning algorithms.

  6. Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

    Miñarro José


    Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

  7. Regularized Reduced Order Models

    Wells, David; Xie, Xuping; Iliescu, Traian


    This paper puts forth a regularization approach for the stabilization of proper orthogonal decomposition (POD) reduced order models (ROMs) for the numerical simulation of realistic flows. Two regularized ROMs (Reg-ROMs) are proposed: the Leray ROM (L-ROM) and the evolve-then-filter ROM (EF-ROM). These new Reg-ROMs use spatial filtering to smooth (regularize) various terms in the ROMs. Two spatial filters are used: a POD projection onto a POD subspace (Proj) and a new POD differential filter (DF). The four Reg-ROM/filter combinations are tested in the numerical simulation of the one-dimensional Burgers equation with a small diffusion coefficient and the three-dimensional flow past a circular cylinder at a low Reynolds number (Re = 100). Overall, the most accurate Reg-ROM/filter combination is EF-ROM-DF. Furthermore, the DF generally yields better results than Proj. Finally, the four Reg-ROM/filter combinations are computationally efficient and generally more accurate than the standard Galerkin ROM.

  8. Regularizing portfolio optimization

    Still, Susanne; Kondor, Imre


    The optimization of large portfolios displays an inherent instability due to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting, which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification 'pressure'. This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade off between the two, depending on the size of the available dataset.

  9. Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

    Vanattou-Saïfoudine, N; McNamara, R; Harkin, A


    Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

  10. k-Walk-Regular Digraphs

    Wen LIU; Jing LIN


    In this paper,we define a class of strongly connected digraph,called the k-walk-regular digraph,study some properties of it,provide its some algebraic characterization and point out that the O-walk-regular digraph is the same as the walk-regular digraph discussed BY Liu and Lin in 2010 and the D-walk-regular digraph is identical with the weakly distance-regular digraph defined by Comellas et al in 2004.

  11. Incidental use of ecstasy: no evidence for harmful effects on cognitive brain function in a prospective fMRI study

    Jager, G.; Win, M.M. de; Vervaeke, H.K.; Schilt, T.; Kahn, R.S.; Brink, W. van den; Ree, J.M. van; Ramsey, M.F.


    Rationale Heavy ecstasy use in humans has been associated with cognitive impairments and changes in cognitive brain function supposedly due to damage to the serotonin system. There is concern that even a single dose of 3,4-methylenedioxymethamphetamine may be neurotoxic, but very little is known ab

  12. A psycho-economic model of ecstasy consumption and related consequences: a multi-site study with community samples.

    Abdallah, Arbi Ben; Scheier, Lawrence M; Inciardi, James A; Copeland, Jan; Cottler, Linda B


    Becker and Murphy's (1988) theory of rational behavior suggests that economic factors play an influential role in the decision leading to drug consumption and possibly dependence. Psychological models, on the other hand, emphasize internal regulatory cues that motivate drug use and play a contributory role in dependence. Until now, the confluence of both economic and psychological models has not been tested empirically. The present study used latent-variable structural equation modeling (SEM) to examine the influence of both economic (social anomie, unit price, and time spent acquiring drugs) and psychological risk factors (motivation, depression, and sexual risk behaviors) on self-reported ecstasy use. Data were obtained from 612 recreational ecstasy users in the United States and Australia participating in a NIDA-funded epidemiological study examining trends in ecstasy use. The sample was mainly white (61%), male (58%), and young (mean age = 23 yrs [5.25]). All of the hypothesized latent constructs were statistically reliable and correlated in the expected direction. A saturated SEM indicated that monetary and opportunity cost, but not income, significantly predicted ecstasy use. Among the psychological measures, motivational cues were the strongest predictor of both use and dependence. Inclusion of gender, age, race, education, and site variables did not appreciably alter the final model parameters. The implications of incorporating the role of economic factors in shaping a more refined understanding of addiction are discussed. Suggestions for future research and study limitations are also noted.

  13. An Analysis of 250 MDMA Addicts%250例苯丙胺类摇头丸(MDMA)滥用人群分析

    孙毅; 徐本树; 王志强; 金俊; 吕秋霖; 张惠民


    目的:了解苯丙胺类物质摇头丸(MDMA)滥用人群人口学特征及其MDMA的精神活性作用.方法:制定统一问卷,对2001年1月-2002年11月在我院住院MDMA滥用者逐一进行登记.结果:总共调查250例摇头丸(MDMA)滥用者.250例MDMA滥用者平均年龄27.25±7.46 a.未婚青年女性141例,占总例数56.6%.文化程度较高,高中以上文化程度165例,占总例数66.04%.滥用方式大多数以啤酒送服,其次是矿泉水、饮料.滥用场所以歌厅和迪厅为主.每周使用2次以上者97例,占38.68%.MDMA的起效时间为25.61±11.06 min,作用持续时间为3.44±1.68 h.滥用后主观感受及行为表现依次为出汗、头晕、口干、心情愉快等.MDMA作用消失后部分滥用者表现为失眠、食欲下降、记忆力减退、厌食、疲乏、睡眠增多、食欲增大等.结论:近年来MDMA滥用者有增多趋势,部分滥用者有向强制性用药的模式趋势发展,应引起人们足够重视.

  14. Annotation of Regular Polysemy

    Martinez Alonso, Hector

    Regular polysemy has received a lot of attention from the theory of lexical semantics and from computational linguistics. However, there is no consensus on how to represent the sense of underspecified examples at the token level, namely when annotating or disambiguating senses of metonymic words...... like “London” (Location/Organization) or “cup” (Container/Content). The goal of this dissertation is to assess whether metonymic sense underspecification justifies incorporating a third sense into our sense inventories, thereby treating the underspecified sense as independent from the literal...

  15. Studies, using in vivo microdialysis, on the effect of the dopamine uptake inhibitor GBR 12909 on 3,4-methylenedioxymethamphetamine ('ecstasy')-induced dopamine release and free radical formation in the mouse striatum.

    Camarero, Jorge; Sanchez, Veronica; O'Shea, Esther; Green, A Richard; Colado, M Isabel


    The present study examined the mechanisms by which 3,4-methylenedioxymethamphetamine (MDMA) produces long-term neurotoxicity of striatal dopamine neurones in mice and the protective action of the dopamine uptake inhibitor GBR 12909. MDMA (30 mg/kg, i.p.), given three times at 3-h intervals, produced a rapid increase in striatal dopamine release measured by in vivo microdialysis (maximum increase to 380 +/- 64% of baseline). This increase was enhanced to 576 +/- 109% of baseline by GBR 12909 (10 mg/kg, i.p.) administered 30 min before each dose of MDMA, supporting the contention that MDMA enters the terminal by diffusion and not via the dopamine uptake site. This, in addition to the fact that perfusion of the probe with a low Ca(2+) medium inhibited the MDMA-induced increase in extracellular dopamine, indicates that the neurotransmitter may be released by a Ca(2+) -dependent mechanism not related to the dopamine transporter. MDMA (30 mg/kg x 3) increased the formation of 2,3-dihydroxybenzoic acid (2,3-DHBA) from salicylic acid perfused through a probe implanted in the striatum, indicating that MDMA increased free radical formation. GBR 12909 pre-treatment attenuated the MDMA-induced increase in 2,3-DHBA formation by approximately 50%, but had no significant intrinsic radical trapping activity. MDMA administration increased lipid peroxidation in striatal synaptosomes, an effect reduced by approximately 60% by GBR 12909 pre-treatment. GBR 12909 did not modify the MDMA-induced changes in body temperature. These data suggest that MDMA-induced toxicity of dopamine neurones in mice results from free radical formation which in turn induces an oxidative stress process. The data also indicate that the free radical formation is probably not associated with the MDMA-induced dopamine release and that MDMA does not induce dopamine release via an action at the dopamine transporter.

  16. Drug Facts

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  17. Drug Facts

    Full Text Available ... Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts ... Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs ...

  18. Drug Facts

    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  19. Drug Facts

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  20. From regular modules to von Neumann regular rings via coordinatization

    Leonard Daus


    Full Text Available In this paper we establish a very close link (in terms of von Neu- mann's coordinatization between regular modules introduced by Zel- manowitz, on one hand, and von Neumann regular rings, on the other hand: we prove that the lattice L^{fg}(M of all finitely generated submodules of a finitely generated regular module M, over an arbitrary ring, can be coordinatized as the lattice of all principal right ideals of some von Neumann regular ring S.

  1. Modular Regularization Algorithms

    Jacobsen, Michael


    The class of linear ill-posed problems is introduced along with a range of standard numerical tools and basic concepts from linear algebra, statistics and optimization. Known algorithms for solving linear inverse ill-posed problems are analyzed to determine how they can be decomposed into indepen......The class of linear ill-posed problems is introduced along with a range of standard numerical tools and basic concepts from linear algebra, statistics and optimization. Known algorithms for solving linear inverse ill-posed problems are analyzed to determine how they can be decomposed...... into independent modules. These modules are then combined to form new regularization algorithms with other properties than those we started out with. Several variations are tested using the Matlab toolbox MOORe Tools created in connection with this thesis. Object oriented programming techniques are explained...... and used to set up the illposed problems in the toolbox. Hereby, we are able to write regularization algorithms that automatically exploit structure in the ill-posed problem without being rewritten explicitly. We explain how to implement a stopping criteria for a parameter choice method based upon...

  2. Structure for Regular Inclusions

    Pitts, David R


    We study pairs (C,D) of unital C*-algebras where D is an abelian C*-subalgebra of C which is regular in C. When D is a MASA in C, there exists a unique completely positive unital map E of C into the injective envelope I(D) of D whose restriction to D is the identity on D. We show that the left kernel of E is the unique closed two-sided ideal of C maximal with respect to having trivial intersection with D. We introduce a new class of well behaved state extensions, the compatible states; we identify compatible states when D is a MASA in C in terms of groups constructed from local dynamics near a pure state on D. When C is separable, D is a MASA in C, and the pair (C,D) is regular, the set of pure states on D with unique state extensions to C is dense in D. The map E can be used as a substitute for a conditional expectation in the construction of coordinates for C relative to D. We show that certain classes of compatible states have natural groupoid operations, and we show that constructions of Kumjian and Renau...

  3. Cough & Cold Medicine Abuse

    ... Know Getting Rid of Old Medicines Dealing With Addiction Understanding Medications and What They Do Prescription Drug Abuse Bath Salts Depressants Ketamine MDMA (Ecstasy) Contact Us Print Resources ...

  4. A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD).

    Oehen, Peter; Traber, Rafael; Widmer, Verena; Schnyder, Ulrich


    Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).

  5. No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation.

    Kim P C Kuypers

    Full Text Available The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg, with or without pindolol (20 mg, oxytocin nasal spray (40 IU+16 IU or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial registration: MDMA & PSB NTR 2636.

  6. Discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine and placebo.

    Johanson, Chris-Ellyn; Kilbey, Marlyne; Gatchalian, Kristin; Tancer, Manuel


    In animals, two-choice drug discrimination studies have demonstrated that the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) are mediated by dopaminergic and serotonergic systems. In order to delineate the relative role of these systems, three-choice paradigms have been used in animals, with findings indicating a more prominent role for serotonin. Human studies assessing the subjective and physiological effects of MDMA have also indicated a mixed action. To parallel animal studies, the participants in the present study were trained to discriminate among a prototypic dopaminergic agonist, d-amphetamine, a prototypic serotonergic agonist, meta-chlorophenylpiperazine (mCPP) and placebo and then were tested with two doses of MDMA. In addition, subjective and physiological effects were measured. The results demonstrated that humans could be trained to discriminate among 20 mg d-amphetamine, 0.75 mg/kg mCPP and placebo. When tested with 1.0 and 1.5 mg/kg, half the participants reported MDMA to be like amphetamine and half like mCPP. There were no clear differences between these two groups in other dimensions, although there was an indication that the individuals who discriminated MDMA as d-amphetamine were more sensitive to the effects of all the drugs. The subjective effects of all three drugs overlapped, although the effects of MDMA appeared more amphetamine-like.

  7. Evolutionary internalized regularities.

    Schwartz, R


    Roger Shepard's proposals and supporting experiments concerning evolutionary internalized regularities have been very influential in the study of vision and in other areas of psychology and cognitive science. This paper examines issues concerning the need, nature, explanatory role, and justification for postulating such internalized constraints. In particular, I seek further clarification from Shepard on how best to understand his claim that principles of kinematic geometry underlie phenomena of motion perception. My primary focus is on the ecological validity of Shepard's kinematic constraint in the context of ordinary motion perception. First, I explore the analogy Shepard draws between internalized circadian rhythms and the supposed internalization of kinematic geometry. Next, questions are raised about how to interpret and justify applying results from his own and others' experimental studies of apparent motion to more everyday cases of motion perception in richer environments. Finally, some difficulties with Shepard's account of the evolutionary development of his kinematic constraint are considered.

  8. 5-HTTLPR Genotype Moderates the Effects of Past Ecstasy Use on Verbal Memory Performance in Adolescent and Emerging Adults: A Pilot Study.

    Natasha E Wright

    Full Text Available Ecstasy use is associated with memory deficits. Serotonin transporter gene (5-HTTLPR polymorphisms have been linked with memory function in healthy samples. The present pilot study investigated the influence of 5-HTTLPR polymorphisms on memory performance in ecstasy users, marijuana-using controls, and non-drug-using controls, after a minimum of 7 days of abstinence.Data were collected from 116 young adults (18-25 years-old, including 45 controls, 42 marijuana users, and 29 ecstasy users, and were balanced for 5-HTTLPR genotype. Participants were abstinent seven days prior to completing memory testing. Three MANCOVAs and one ANCOVA were run to examine whether drug group, 5-HTTLPR genotype, and their interactions predicted verbal and visual memory after controlling for gender, past year alcohol use, other drug use, and nicotine cotinine levels.MANCOVA and ANCOVA analysis revealed a significant interaction between drug group and genotype (p = .03 such that ecstasy users with the L/L genotype performed significantly worse on CVLT-2 total recall (p = .05, short (p = .008 and long delay free recall (p = .01, and recognition (p = .006, with the reverse pattern found in controls. Ecstasy did not significantly predict visual memory. 5-HTTLPR genotype significantly predicted memory for faces (p = .02; short allele carriers performed better than those with L/L genotype.5-HTTLPR genotype moderated the effects of ecstasy on verbal memory, with L/L carriers performing worse compared to controls. Future research should continue to examine individual differences in ecstasy's impact on neurocognitive performance as well as relationships with neuronal structure. Additional screening and prevention efforts focused on adolescents and emerging adults are necessary to prevent ecstasy consumption.

  9. Adaptive Regularization of Neural Classifiers

    Andersen, Lars Nonboe; Larsen, Jan; Hansen, Lars Kai


    We present a regularization scheme which iteratively adapts the regularization parameters by minimizing the validation error. It is suggested to use the adaptive regularization scheme in conjunction with optimal brain damage pruning to optimize the architecture and to avoid overfitting. Furthermo...

  10. Drug intelligence based on MDMA tablets data I. Organic impurities profiling.

    Weyermann, Céline; Marquis, Raymond; Delaporte, Céline; Esseiva, Pierre; Lock, Eric; Aalberg, Laura; Bozenko, Joseph S; Dieckmann, Susanne; Dujourdy, Laurence; Zrcek, Frantisek


    The main objectives of the European project "Collaborative Harmonization of Methods for Profiling of Amphetamine Type Stimulants" (CHAMP) funded by the sixth framework programme of the European Commission, included the harmonization of MDMA profiling methods and the creation of a common database in a drug intelligence perspective. In the preliminary stages of this project, the participating laboratories analysed the physical characteristics, the chemical composition and the organic impurities of MDMA tablets, using the previously harmonized methods. The aim of the present work was to apply statistical treatments to the recorded data in order to evaluate their potential in the fight against drug trafficking. Comparable working procedures were applied on the different types of data. The first part of this article deals with organic impurities data, while the second part focuses on the potential of the physical characteristics. Organic impurities data were recorded by a harmonized Gas Chromatography/Mass Spectrometry (GC/MS) method previously developed. Statistical analysis provided a selection of pertinent variables among the 46 organic impurities identified in the chromatograms. Correlation coefficients were used to yield separation between populations of samples coming from the same synthesis batch and samples coming from different batches. It was shown that correlation measurements based on Pearson and cosine functions applied to the data pre-treated by normalisation to the sum of peak responses followed by the square root provided an excellent discrimination between the two populations. The statistical methods applied to organic impurities profiles proved to be excellent techniques to differentiate samples from different batches and to highlight operational links between samples.

  11. Determination of MDMA and MDA in rat urine by semi-micro column HPLC-fluorescence detection with DBD-F and their monitoring after MDMA administration to rat.

    Wada, Mitsuhiro; Nakamura, Shinichi; Tomita, Mamoru; Nakashima, Mihoko N; Nakashima, Kenichiro


    A simultaneous semi-micro column HPLC method with fluorescence detection of abused drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), amphetamine (AP) and methamphetamine (MP) in rat urine was examined by using 4-(N,N-dimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) as a labelling reagent and alpha-phenylethylamine as an internal standard (IS). A sample (50 microL) of rat urine was added to 5 microL IS and 100 microL 100 mmol/L borate buffer (pH 12) and extracted with 1.5 mL n-hexane. After evaporation, 50 microL 75 mmol/L borate buffer (pH 8.5) and 50 microL 20 mmol/L DBD-F in CH3CN were added to the residue and mixed well. The resultant solution was heated for 20 min at 80 degrees C and then cooled in an ice bath. A good separation of DBD-derivatives could be achieved within 45 min using a semi-micro ODS column with an eluent of CH3CN/CH3OH/10 mmol/L imidazole-HNO3 buffer (pH 7.0) (= 45:5:50, v/v/v %). The DBD derivatives were monitored at 565 nm with an excitation at 470 nm. The calibration curves showed good linearity (r = 0.997) with 0.5-15 ng/mL detection limits at a S/N ratio of 3. MDMA and MDA in rat urine could be monitored for 15 h after a single administration of MDMA to rat (2.0 mg/kg, i.p.). The concentrations for MDMA and MDA (n = 3) were 0.13-160.1 and 0.17-10.9 microg/mL, respectively.

  12. The effect of 3,4-methylenedioxymethamphetamine ('Ecstasy') on serotonergic regulation of the mammalian circadian clock mechanism in rats: the role of dopamine and hyperthermia.

    Dafters, Richard I; Biello, Stephany M


    The recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is known to be a neurotoxin for serotonergic axons ascending from the raphe nucleus including those which terminate on neurons of the suprachiasmatic nuclei (SCN) of the hypothalamus, the putative mammalian circadian clock. Since dopamine release has been implicated in the serotonergic neurotoxicity, we examined the effects of the dopamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) and the D2 receptor antagonist haloperidol (HAL) on the long-term effect of MDMA on serotonergic regulation of the SCN neuronal firing rhythm. Co-administration of AMPT or HAL with MDMA eliminated the acute hyperthermic response but had no effect on the MDMA-induced phase shift in the firing rhythm of SCN neurons to the selective 5-HT1A receptor agonist, 8-hydroxy-2-(dipropylamino)-tetralin. It is concluded that neither dopamine metabolism nor hyperthermia account for the altered serotonergic function in the SCN produced by MDMA. Toxic free radical production following MDMA metabolism may be responsible.

  13. Rotating regular black holes

    Bambi, Cosimo


    The formation of spacetime singularities is a quite common phenomenon in General Relativity and it is regulated by specific theorems. It is widely believed that spacetime singularities do not exist in Nature, but that they represent a limitation of the classical theory. While we do not yet have any solid theory of quantum gravity, toy models of black hole solutions without singularities have been proposed. So far, there are only non-rotating regular black holes in the literature. These metrics can be hardly tested by astrophysical observations, as the black hole spin plays a fundamental role in any astrophysical process. In this letter, we apply the Newman-Janis algorithm to the Hayward and to the Bardeen black hole metrics. In both cases, we obtain a family of rotating solutions. Every solution corresponds to a different matter configuration. Each family has one solution with special properties, which can be written in Kerr-like form in Boyer-Lindquist coordinates. These special solutions are of Petrov type ...

  14. Rotating regular black holes

    Bambi, Cosimo, E-mail:; Modesto, Leonardo, E-mail:


    The formation of spacetime singularities is a quite common phenomenon in General Relativity and it is regulated by specific theorems. It is widely believed that spacetime singularities do not exist in Nature, but that they represent a limitation of the classical theory. While we do not yet have any solid theory of quantum gravity, toy models of black hole solutions without singularities have been proposed. So far, there are only non-rotating regular black holes in the literature. These metrics can be hardly tested by astrophysical observations, as the black hole spin plays a fundamental role in any astrophysical process. In this Letter, we apply the Newman–Janis algorithm to the Hayward and to the Bardeen black hole metrics. In both cases, we obtain a family of rotating solutions. Every solution corresponds to a different matter configuration. Each family has one solution with special properties, which can be written in Kerr-like form in Boyer–Lindquist coordinates. These special solutions are of Petrov type D, they are singularity free, but they violate the weak energy condition for a non-vanishing spin and their curvature invariants have different values at r=0 depending on the way one approaches the origin. We propose a natural prescription to have rotating solutions with a minimal violation of the weak energy condition and without the questionable property of the curvature invariants at the origin.

  15. Ensemble manifold regularization.

    Geng, Bo; Tao, Dacheng; Xu, Chao; Yang, Linjun; Hua, Xian-Sheng


    We propose an automatic approximation of the intrinsic manifold for general semi-supervised learning (SSL) problems. Unfortunately, it is not trivial to define an optimization function to obtain optimal hyperparameters. Usually, cross validation is applied, but it does not necessarily scale up. Other problems derive from the suboptimality incurred by discrete grid search and the overfitting. Therefore, we develop an ensemble manifold regularization (EMR) framework to approximate the intrinsic manifold by combining several initial guesses. Algorithmically, we designed EMR carefully so it 1) learns both the composite manifold and the semi-supervised learner jointly, 2) is fully automatic for learning the intrinsic manifold hyperparameters implicitly, 3) is conditionally optimal for intrinsic manifold approximation under a mild and reasonable assumption, and 4) is scalable for a large number of candidate manifold hyperparameters, from both time and space perspectives. Furthermore, we prove the convergence property of EMR to the deterministic matrix at rate root-n. Extensive experiments over both synthetic and real data sets demonstrate the effectiveness of the proposed framework.

  16. Don Delillo’s Point Omega; Ecstasy and Inertia in a Hyperreal World: A Baudrillardian Reading

    Faeze Yegane


    Full Text Available This paper aims to present a Baudrillardian reading of Don Delillo’s Point Omega in the framework of Baudrillard’s definition of the contemporary world as ‘hyperreal’ and also his twin concepts of ‘ecstasy and inertia’. According to Baudrillard, the contemporary time is the hyperreal era in which subjects do not have access to ‘real’ primarily because they are supplied with the ‘simulations’ first and then with the ‘real’ entity and probably never confronted with the ‘real’ itself through media, advertisements, and virtual world. Thus, the perception they have from incidents, objects, places and even other people is ‘hyperreal’; edited, censored, beautified and exaggerated versions of reality; more real than real. In this study Point Omega will be examined as Delillo’s ‘hyperreal’ version of Alfred Hitchcock’s Psycho since the movie is screened in the course of the novel and despite the similarities between the novel and the movie they end contrastingly. Symbolically ‘real’ is not found in the novel due to ‘Mobius spiraling negativity’ which is one of the features of Baudrillard’s definition of ‘hyperreal’ age. Baudrillard believes in the triumph of objects over subjects. While the object’s world is perpetually cultivating frenziedly, objects and technologies begin to dominate the stupefied subjects consequently he states when the objects are moving toward their ‘ecstasy’, the subjects are stricken in ‘inertia’. This supremacy of objects and technologies will be displayed in Point Omega regarding Richard Elster’s inert behavior and reaching the ‘omega point’ that Teilhard de Chardin envisions for human race is rendered impossible due to Elster’s destiny in the framework of Baudrillard’s concept of evolution.   Keywords: Ecstasy, Inertia, Hyperreality, Baudrillard, Don Delillo, Point Omega, Omega Point, Teilhard de Chardin, Alfred Hitchcock.

  17. MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.

    Kiyatkin, Eugene A; Ren, Suelynn E


    Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential

  18. Cocaine, MDMA and methamphetamine residues in wastewater: Consumption trends (2009-2015) in South East Queensland, Australia.

    Lai, Foon Yin; O'Brien, Jake W; Thai, Phong K; Hall, Wayne; Chan, Gary; Bruno, Raimondo; Ort, Christoph; Prichard, Jeremy; Carter, Steve; Anuj, Shalona; Kirkbride, K Paul; Gartner, Coral; Humphries, Melissa; Mueller, Jochen F


    Wastewater analysis, or wastewater-based epidemiology, has become a common tool to monitor trends of illicit drug consumption around the world. In this study, we examined trends in cocaine, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine consumption by measuring their residues in wastewater from two wastewater treatment plants in Australia (specifically, an urban and a rural catchment, both in South East Queensland) between 2009 and 2015. With direct injection of the samples, target analytes were identified and quantified using liquid chromatography-mass spectrometry. Cocaine and MDMA residues and metabolites were mainly quantifiable in the urban catchment while methamphetamine residues were consistently detected in both urban and rural catchments. There was no consistent trend in the population normalised mass loads observed for cocaine and MDMA at the urban site between 2009 and 2015. In contrast, there was a five-fold increase in methamphetamine consumption over this period in this catchment. For methamphetamine consumption, the rural area showed a very similar trend as the urban catchment starting at a lower baseline. The observed increase in per capita loads of methamphetamine via wastewater analysis over the past six years in South East Queensland provides objective evidence for increased methamphetamine consumption in the Australian population while the use of other illicit stimulants remained relatively stable.

  19. Stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solution.

    Maskell, Peter D; Seetohul, L Nitin; Livingstone, Alison C; Cockburn, Alexandra K; Preece, Jamie; Pounder, Derrick J


    Occasionally, the only postmortem samples available for analysis are contaminated with formaldehyde, either due to embalming prior to sampling or because analysis is carried out only when formalin-fixed tissues retained for histological study are available. Formaldehyde reacts with several drugs of forensic interest that contain either a primary or a secondary amine group to form their N-methyl derivatives. We investigated the stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solutions using three different formaldehyde concentrations (5, 10 and 20%) and three different pHs (3.0, 7.0 and 9.5). Analysis was performed using high-performance liquid chromatography with diode array detection to determine the percentage degradation of each drug over time, up to 60 days. MDMA, mephedrone and 3-TFMPP are unstable in formalin solutions, with the degradation rate increasing with increasing pH. After 28 days in 20% formalin, pH 9.5, there remained 57% of the initial 3-TFMPP concentration, 11% of the initial MDMA concentration and 4% of the initial mephedrone concentration. Forensic toxicologists should be aware that, when analyzing for these drugs in an embalmed body or in tissues stored in formalin solutions, the methylated form of the secondary amine-containing drug could be a more useful analyte than the parent drug.

  20. Forensic Identification of Ecstasy(MDMA) by Pattern Recognition%亚甲二氧基甲基苯丙胺法庭鉴定的化学模式识别研究

    吴国萍; 蔡锡兰; 相秉仁



  1. Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells.

    Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Rice, Kenner C; Gannon, Brenda M; Fantegrossi, William E; Gonzalez, Carmen; Paule, Merle G; Ali, Syed F


    Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5mM, with similar effects observed after MDPV exposures starting at 1mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced disruption of the endothelial monolayer from 1mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥0.5mM without vacuole formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic. Published by Elsevier Ireland Ltd.

  2. Visione, possessione, estasi: sulla teoria della trance rituale - Vision, possession, ecstasy: on the theory of ritual trance

    Antonio Luigi Palmisano


    Full Text Available The ritual trances are the expression of the institutionalization of modified states of consciousness. This essay identifies and proposes three major paradigms of institutionalization – vision, possession and ecstasy – and proceeds then to the analysis of the modes and modalities of ritualization and institutionalization of modified states of consciousness – initiation, therapy, liturgy and divination – which lead to a thematization of the structure of trance. Beginning with the discussion of the preceding ethnographies which contribute to the elaboration of a new general theory of trance and are at the same time the result of this same theory of trance – certainly not wholly formulated although much has been done – the author examines the ethnographic material on the zar cults of Ethiopia on the basis of his many years fieldwork in Ethiopia and in other ethnic, social, political and cultural contexts, always concentrated on ritual trances of vision, possession and ecstasy.

  3. Regular Bisimple ω2-semigroups

    汪立民; 商宇


    @@ The regular semigroups S with an idempotent set Es = {e0,e1,…,en,…} such that e0 > e1 >…> en >… is called a regular ω-semigroup. In [5] Reilly determined the structure of a regular bisimple ω-semigroup as BR(G,θ),which is the classical Bruck-Reilly extension of a group G.

  4. Completely regular fuzzifying topological spaces

    A. K. Katsaras


    Full Text Available Some of the properties of the completely regular fuzzifying topological spaces are investigated. It is shown that a fuzzifying topology τ is completely regular if and only if it is induced by some fuzzy uniformity or equivalently by some fuzzifying proximity. Also, τ is completely regular if and only if it is generated by a family of probabilistic pseudometrics.

  5. On regular rotating black holes

    Torres, R.; Fayos, F.


    Different proposals for regular rotating black hole spacetimes have appeared recently in the literature. However, a rigorous analysis and proof of the regularity of this kind of spacetimes is still lacking. In this note we analyze rotating Kerr-like black hole spacetimes and find the necessary and sufficient conditions for the regularity of all their second order scalar invariants polynomial in the Riemann tensor. We also show that the regularity is linked to a violation of the weak energy conditions around the core of the rotating black hole.

  6. Constrained and regularized system identification

    Tor A. Johansen


    Full Text Available Prior knowledge can be introduced into system identification problems in terms of constraints on the parameter space, or regularizing penalty functions in a prediction error criterion. The contribution of this work is mainly an extension of the well known FPE (Final Production Error statistic to the case when the system identification problem is constrained and contains a regularization penalty. The FPECR statistic (Final Production Error with Constraints and Regularization is of potential interest as a criterion for selection of both regularization parameters and structural parameters such as order.

  7. On regular rotating black holes

    Torres, Ramon


    Different proposals for regular rotating black hole spacetimes have appeared recently in the literature. However, a rigorous analysis and proof of the regularity of this kind of spacetimes is still lacking. In this note we analyze rotating Kerr-like black hole spacetimes and find the necessary and sufficient conditions for the regularity of all their second order scalar invariants polynomial in the Riemann tensor. We also show that the regularity is linked to a violation of the weak energy conditions around the core of the rotating black hole.

  8. On Ideals of Regular Rings

    CHEN Huan Yin; LI Fu An


    In this paper, we investigate ideals of regular rings and give several characterizations for an ideal to satisfy the comparability. In addition, it is shown that, if Ⅰ is a minimal two-sided ideal of a regular ring R, then Ⅰ satisfies the comparability if and only if Ⅰ is separative. Furthermore, we prove that, for ideals with stable range one, Roth's problem has an affirmative solution. These extend the corresponding results on unit-regularity and one-sided unit-regularity.

  9. Visione, possessione, estasi: sulla teoria della trance rituale - Vision, possession, ecstasy: on the theory of ritual trance

    Antonio Luigi Palmisano


    The ritual trances are the expression of the institutionalization of modified states of consciousness. This essay identifies and proposes three major paradigms of institutionalization – vision, possession and ecstasy – and proceeds then to the analysis of the modes and modalities of ritualization and institutionalization of modified states of consciousness – initiation, therapy, liturgy and divination – which lead to a thematization of the structure of trance. Beginning with the d...

  10. Using Cluster Analysis and ICP-MS to Identify Groups of Ecstasy Tablets in Sao Paulo State, Brazil.

    Maione, Camila; de Oliveira Souza, Vanessa Cristina; Togni, Loraine Rezende; da Costa, José Luiz; Campiglia, Andres Dobal; Barbosa, Fernando; Barbosa, Rommel Melgaço


    The variations found in the elemental composition in ecstasy samples result in spectral profiles with useful information for data analysis, and cluster analysis of these profiles can help uncover different categories of the drug. We provide a cluster analysis of ecstasy tablets based on their elemental composition. Twenty-five elements were determined by ICP-MS in tablets apprehended by Sao Paulo's State Police, Brazil. We employ the K-means clustering algorithm along with C4.5 decision tree to help us interpret the clustering results. We found a better number of two clusters within the data, which can refer to the approximated number of sources of the drug which supply the cities of seizures. The C4.5 model was capable of differentiating the ecstasy samples from the two clusters with high prediction accuracy using the leave-one-out cross-validation. The model used only Nd, Ni, and Pb concentration values in the classification of the samples. © 2017 American Academy of Forensic Sciences.

  11. The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    Goudie, Andrew J; Sumnall, Harry R; Field, Matt; Clayton, Hannah; Cole, Jon C


    Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

  12. Regularly timed events amid chaos

    Blakely, Jonathan N.; Cooper, Roy M.; Corron, Ned J.


    We show rigorously that the solutions of a class of chaotic oscillators are characterized by regularly timed events in which the derivative of the solution is instantaneously zero. The perfect regularity of these events is in stark contrast with the well-known unpredictability of chaos. We explore some consequences of these regularly timed events through experiments using chaotic electronic circuits. First, we show that a feedback loop can be implemented to phase lock the regularly timed events to a periodic external signal. In this arrangement the external signal regulates the timing of the chaotic signal but does not strictly lock its phase. That is, phase slips of the chaotic oscillation persist without disturbing timing of the regular events. Second, we couple the regularly timed events of one chaotic oscillator to those of another. A state of synchronization is observed where the oscillators exhibit synchronized regular events while their chaotic amplitudes and phases evolve independently. Finally, we add additional coupling to synchronize the amplitudes, as well, however in the opposite direction illustrating the independence of the amplitudes from the regularly timed events.

  13. Online co-regularized algorithms

    Ruijter, T. de; Tsivtsivadze, E.; Heskes, T.


    We propose an online co-regularized learning algorithm for classification and regression tasks. We demonstrate that by sequentially co-regularizing prediction functions on unlabeled data points, our algorithm provides improved performance in comparison to supervised methods on several UCI benchmarks

  14. Online co-regularized algorithms

    Ruijter, T. de; Tsivtsivadze, E.; Heskes, T.


    We propose an online co-regularized learning algorithm for classification and regression tasks. We demonstrate that by sequentially co-regularizing prediction functions on unlabeled data points, our algorithm provides improved performance in comparison to supervised methods on several UCI benchmarks

  15. The synthesis and characterisation of MDMA derived from a catalytic oxidation of material isolated from black pepper reveals potential route specific impurities.

    Plummer, Christopher M; Breadon, Thomas W; Pearson, James R; Jones, Oliver A H


    This work examines the chemical synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA) from piperonal prepared via a catalytic ruthenium tetroxide oxidation of piperine extracted from black pepper. A variety of oxidation conditions were experimented with including different solvent systems and co-oxidants. A sample of prepared piperonal was successfully converted into MDMA via 3,4-methylenedioxyphenyl-2-nitropropene (MDP2NP) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) and the impurities within each product characterised by GC-MS to give a contaminant profile of the synthetic pathway. Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation process by an as yet unknown mechanism. This impurity reacted alongside piperonal to give chlorinated analogues of each precursor, ultimately yielding 2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA) as an impurity within the MDMA sample. The methodology developed is a simple way to synthesise a substantial amount of precursor material with easy to obtain reagents. The results also show that chlorinated MDMA analogues, previously thought to be deliberately included adulterants, may in fact be route specific impurities with potential application in determining the origin and synthesis method of seized illicit drugs.

  16. Nonconvex Regularization in Remote Sensing

    Tuia, Devis; Flamary, Remi; Barlaud, Michel


    In this paper, we study the effect of different regularizers and their implications in high dimensional image classification and sparse linear unmixing. Although kernelization or sparse methods are globally accepted solutions for processing data in high dimensions, we present here a study on the impact of the form of regularization used and its parametrization. We consider regularization via traditional squared (2) and sparsity-promoting (1) norms, as well as more unconventional nonconvex regularizers (p and Log Sum Penalty). We compare their properties and advantages on several classification and linear unmixing tasks and provide advices on the choice of the best regularizer for the problem at hand. Finally, we also provide a fully functional toolbox for the community.

  17. Conservative regularization of compressible flow

    Krishnaswami, Govind S; Thyagaraja, Anantanarayanan


    Ideal Eulerian flow may develop singularities in vorticity w. Navier-Stokes viscosity provides a dissipative regularization. We find a local, conservative regularization - lambda^2 w times curl(w) of compressible flow and compressible MHD: a three dimensional analogue of the KdV regularization of the one dimensional kinematic wave equation. The regulator lambda is a field subject to the constitutive relation lambda^2 rho = constant. Lambda is like a position-dependent mean-free path. Our regularization preserves Galilean, parity and time-reversal symmetries. We identify locally conserved energy, helicity, linear and angular momenta and boundary conditions ensuring their global conservation. Enstrophy is shown to remain bounded. A swirl velocity field is identified, which transports w/rho and B/rho generalizing the Kelvin-Helmholtz and Alfven theorems. A Hamiltonian and Poisson bracket formulation is given. The regularized equations are used to model a rotating vortex, channel flow, plane flow, a plane vortex ...

  18. Approximate Sparse Regularized Hyperspectral Unmixing

    Chengzhi Deng


    Full Text Available Sparse regression based unmixing has been recently proposed to estimate the abundance of materials present in hyperspectral image pixel. In this paper, a novel sparse unmixing optimization model based on approximate sparsity, namely, approximate sparse unmixing (ASU, is firstly proposed to perform the unmixing task for hyperspectral remote sensing imagery. And then, a variable splitting and augmented Lagrangian algorithm is introduced to tackle the optimization problem. In ASU, approximate sparsity is used as a regularizer for sparse unmixing, which is sparser than l1 regularizer and much easier to be solved than l0 regularizer. Three simulated and one real hyperspectral images were used to evaluate the performance of the proposed algorithm in comparison to l1 regularizer. Experimental results demonstrate that the proposed algorithm is more effective and accurate for hyperspectral unmixing than state-of-the-art l1 regularizer.

  19. Regular Small-World Network

    ZOU Zhi-Yun; MAO Bao-Hua; HAO Hai-Ming; GAO Jian-Zhi; YANG Jie-Jiao


    According to the deficiencies in Watts and Strogatz's small-world network model, we present a new regular model to establish the small-world network. Besides the property of the small-world, this model has other properties such as accuracy in controlling the average shortest path length L, and the average clustering coefficient C, also regular network topology as well as enhanced network robustness. This method improves the construction of the small-world network essentially, so that the regular small-world network closely resembles the actual network. We also present studies on the relationships among the quantities of a variety of edges, L and C in regular small-world network in detail. This research lays the foundation for the establishment of the regular small-world network and acts as a good guidance for further research of this model and its applications.

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

    Silvio Fernandes Lapachinske


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

  1. Recent updates on drug abuse analyzed by neuroproteomics studies: Cocaine, Methamphetamine and MDMA

    Firas Kobeissy


    Full Text Available Currently, drug abuse and addiction represent a global public health concern with about 13.6 million people using illicit drugs in the USA alone. Substance abuse intervenes in normal brain functioning, causing alterations in memory, behavior and neuronal physiology. Although many studies have been conducted to elucidate the mode of action of different drugs, the heterogeneous modes of drug intake led to a complicated profile of drug-induced brain changes involving neurotoxicity and addiction. Given the complex interplay of genes and proteins in mediating these effects, neuroproteomics analysis has been considered among the methods of choice to complement what has already been discovered and to create targeted therapies. In this review, we will focus on three drugs, namely cocaine, methamphetamine (METH and 3,4-methylenedioxy-N-methylamphetamine (MDMA. In the context of neuroproteomics, these drugs have been extensively studied by utilizing different experimental models, including primate and non-primate animals along with postmortem human samples. Even though there are many variations in the results, these drugs were shown to employ common pathways in eliciting their effects. Neuroproteomics analysis of these drugs has led to the identification of differentially expressed proteins involved in metabolism, oxidative stress, cell signaling, cytoskeleton, cell death and synaptic plasticity. Finally, this work will discuss recent findings from our laboratory by looking at a model of chronic methamphetamine abuse and its effect on different brain regions.

  2. A long hangover from party drugs: residual proteomic changes in the hippocampus of rats 8 weeks after γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination.

    van Nieuwenhuijzen, Petra S; Kashem, Mohammed A; Matsumoto, Izuru; Hunt, Glenn E; McGregor, Iain S


    3,4-Methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate (GHB) are popular party drugs that are used for their euphoric and prosocial effects, and sometimes in combination. Both drugs increase markers of oxidative stress in the hippocampus and can cause lasting impairments in hippocampal-dependent forms of memory. To gain further information on the biochemical mechanisms underlying these effects, the current study examined residual changes in hippocampal protein expression measured 8 weeks after chronic administration of GHB (500mg/kg), MDMA (5mg/kg) or their combination (GHB/MDMA). The drugs were administered once a day for 10 days in an environment with an elevated ambient temperature of 28 degrees C. Results showed significant changes in protein expression, relative to controls, in all three groups: MDMA and GHB given alone caused residual changes in 8 and 5 proteins respectively, while the GHB/MDMA combination significantly changed 6 proteins. The altered proteins had roles in neuroplasticity, neuroprotection, intracellular signalling and cytoskeletal function. The largest change (-4.3-fold) was seen in the MDMA group with the protein C-crk: a protein implicated in learning-related neuroplasticity. The second largest change (3.0-fold) was seen in the GHB group in Glutathione-S-transferase (GST), a protein that protects against oxidative stress. Two cytoskeletal proteins (Tubulin Folding Cofactor B and Tropomyosin-alpha-3 chain) and one plasticity related protein (Neuronal Pentraxin-1 NP1) were similarly changed in both the MDMA and the GHB groups, while two intracellular signalling proteins (alpha-soluble NSF-attachment protein and subunits of the V-type proton ATPase) were changed in both the MDMA/GHB and the MDMA groups. These results provide some insight into the molecular pathways possibly underlying the lasting cognitive deficits arising from GHB and/or MDMA use.

  3. A Criterion for Regular Sequences

    D P Patil; U Storch; J Stückrad


    Let be a commutative noetherian ring and $f_1,\\ldots,f_r \\in R$. In this article we give (cf. the Theorem in $\\mathcal{x}$2) a criterion for $f_1,\\ldots,f_r$ to be regular sequence for a finitely generated module over which strengthens and generalises a result in [2]. As an immediate consequence we deduce that if $V(g_1,\\ldots,g_r) \\subseteq V(f_1,\\ldots,f_r)$ in Spec and if $f_1,\\ldots,f_r$ is a regular sequence in , then $g_1,\\ldots,g_r$ is also a regular sequence in .

  4. On Regular Power-Substitution

    Huanyin CHEN


    The necessary and sufficient conditions under which a ring satisfies regular power-substitution are investigated. It is shown that a ring R satisfies regular power-substitution if and only if a(-~)b in R implies that there exist n ∈ N and a U ∈ GLn(R) such that aU =Ub if and only if for any regular x ∈ R there exist m,n ∈ N and U ∈ GLn(R) such that xmIn = xmUxm, where a(-~)b means that there exists x, y, z ∈ R such that a = ybx, b = xaz and x = xyx = xzx. It is proved that every directly finite simple ring satisfies regular power-substitution. Some applications for stably free R-modules are also obtained.


    CHARTRAND, RICK [Los Alamos National Laboratory


    The authors show that using a nonconvex penalty term to regularize image reconstruction can substantially improve the preservation of object shapes. The commonly-used total-variation regularization, {integral}|{del}u|, penalizes the length of the object edges. They show that {integral}|{del}u|{sup p}, 0 < p < 1, only penalizes edges of dimension at least 2-p, and thus finite-length edges not at all. We give numerical examples showing the resulting improvement in shape preservation.

  6. Regularization with a pruning prior

    Goutte, Cyril; Hansen, Lars Kai


    We investigate the use of a regularization priorthat we show has pruning properties. Analyses areconducted both using a Bayesian framework and withthe generalization method, on a simple toyproblem. Results are thoroughly compared withthose obtained with a traditional weight decay.......We investigate the use of a regularization priorthat we show has pruning properties. Analyses areconducted both using a Bayesian framework and withthe generalization method, on a simple toyproblem. Results are thoroughly compared withthose obtained with a traditional weight decay....

  7. Regular and Periodic Tachyon Kinks

    Bazeia, D.; Menezes, R.; Ramos, J. G.


    We search for regular tachyon kinks in an extended model, which includes the tachyon action recently proposed to describe the tachyon field. The extended model that we propose adds a new contribution to the tachyon action, and seems to enrich the present scenario for the tachyon field. We have found stable tachyon kinks of regular profile, which may appropriately lead to the singular kink found by Sen sometime ago. Also, under specific conditions we may find periodic array of kink-antikink co...

  8. Commuting Π-regular rings

    Shervin Sahebi


    Full Text Available ‎$R$ is called commuting regular ring (resp‎. ‎semigroupif‎ for each $x,y\\in R$ there exists $a\\in R$‎ such that$xy=yxayx$‎. ‎In this paper‎, ‎we introduce the concept of‎‎commuting $\\pi$-regular rings (resp‎. ‎semigroups and‎‎study various properties of them.

  9. Condition Number Regularized Covariance Estimation.

    Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala


    Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the "large p small n" setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required.

  10. Condition Number Regularized Covariance Estimation*

    Won, Joong-Ho; Lim, Johan; Kim, Seung-Jean; Rajaratnam, Bala


    Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the “large p small n” setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required. PMID:23730197

  11. The Study of MDMA Toxicity%3,4亚甲二氧基甲基苯丙胺的机体毒性研究

    王雪; 彭祖贵; 况伟宏; 王康林; 陈勇军; 黄明生; 孙学礼



  12. Sex-dependent effects of early maternal deprivation on MDMA-induced conditioned place preference in adolescent rats: possible neurochemical correlates.

    Llorente-Berzal, Alvaro; Manzanedo, Carmen; Daza-Losada, Manuel; Valero, Manuel; López-Gallardo, Meritxell; Aguilar, María A; Rodríguez-Arias, Marta; Miñarro, José; Viveros, Maria-Paz


    The early neonatal stage constitutes a sensitive period during which exposure to adverse events can increase the risk of neuropsychiatric disorders. Maternal deprivation (MD) is a model of early life stress that induces long-term behavioural and physiological alterations, including susceptibility to different drugs of abuse. In the present study we have used the conditioned place preference (CPP) paradigm to address the influence of MD on the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in adolescent animals of both sexes. We have previously observed in adolescent rats that MD induces modifications in the serotonergic and endocannabinoid systems, which play a role in the rewarding effects of MDMA. In light of this evidence, we hypothesized that MD would alter the psychobiological consequences of exposure to MDMA. Neonatal Wistar rats underwent MD (24h, on PND 9) or were left undisturbed (controls). The animals were conditioned with 2.5mg/kg MDMA during the periadolescent period (PND 34-PND 43) and were tested in the open-field test at the end of adolescence (PND 60). Animals were sacrificed on PND 68-75 and levels of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid were measured in the striatum, hippocampus and cortex, while the expression of hippocampal CB1 cannabinoid receptor (CB1R) and circulating levels of corticosterone and leptin were also measured. Control males showed CPP after administration of MDMA. However, no MDMA-induced CPP was detected in control females or MD males, and MD had no effect on open field activity in any group. A reduction in striatal and cortical 5-HT levels, increased expression of hippocampal CB1R and a marked trend towards higher circulating leptin levels were observed in MDMA-treated MD males. Our results demonstrate for the first time that MD reduces the rewarding effects of MDMA in a sex-dependent manner. We propose that this effect is related, at least in part, with alterations of the serotonergic

  13. 固相微萃取与气质联用法检测尿中MDMA

    厉开平; 周欣; 赵志新; 朱昱



  14. Quotient Complexity of Regular Languages

    Janusz Brzozowski


    Full Text Available The past research on the state complexity of operations on regular languages is examined, and a new approach based on an old method (derivatives of regular expressions is presented. Since state complexity is a property of a language, it is appropriate to define it in formal-language terms as the number of distinct quotients of the language, and to call it "quotient complexity". The problem of finding the quotient complexity of a language f(K,L is considered, where K and L are regular languages and f is a regular operation, for example, union or concatenation. Since quotients can be represented by derivatives, one can find a formula for the typical quotient of f(K,L in terms of the quotients of K and L. To obtain an upper bound on the number of quotients of f(K,L all one has to do is count how many such quotients are possible, and this makes automaton constructions unnecessary. The advantages of this point of view are illustrated by many examples. Moreover, new general observations are presented to help in the estimation of the upper bounds on quotient complexity of regular operations.

  15. Regular

    Ratanpal B S; Sharma Jaita


    The charged anisotropic star on paraboloidal space-time is reported by choosing a particular form of radial pressure and electric field intensity. The non-singular solution of Einstein–Maxwell system of equation has been derived and it is shown that the model satisfies all the physical plausibility conditions. It is observed that in the absence of electric field intensity, the model reducesto a particular case of uncharged Sharma and Ratanpal model. It is also observed that the parameter used in the electric field intensity directly affects mass of the star.

  16. Comparing probability and non-probability sampling methods in Ecstasy research: implications for the internet as a research tool.

    Miller, Peter G; Johnston, Jennifer; Dunn, Matthew; Fry, Craig L; Degenhardt, Louisa


    The usage of Ecstasy and related drug (ERD) has increasingly been the focus of epidemiological and other public health-related research. One of the more promising methods is the use of the Internet as a recruitment and survey tool. However, there remain methodological concerns and questions about representativeness. Three samples of ERD users in Melbourne, Australia surveyed in 2004 are compared in terms of a number of key demographic and drug use variables. The Internet, face-to-face, and probability sampling methods appear to access similar but not identical groups of ERD users. Implications and limitations of the study are noted and future research is recommended.

  17. Preliminary evidence of motor impairment among polysubstance 3,4-methylenedioxymethamphetamine users with intact neuropsychological functioning.

    Bousman, Chad A; Cherner, Mariana; Emory, Kristen T; Barron, Daniel; Grebenstein, Patricia; Atkinson, J Hampton; Heaton, Robert K; Grant, Igor


    Neuropsychological disturbances have been reported in association with use of the recreational drug "ecstasy," or 3,4-methylenedioxymethamphetamine (MDMA), but findings have been inconsistent. We performed comprehensive neuropsychological testing examining seven ability domains in 21 MDMA users (MDMA+) and 21 matched control participants (MDMA-). Among MDMA+ participants, median [interquartile range] lifetime MDMA use was 186 [111, 516] doses, with 120 [35-365] days of abstinence. There were no significant group differences in neuropsychological performance, with the exception of the motor speed/dexterity domain in which 43% of MDMA+ were impaired compared with 5% of MDMA- participants (p = .004). Motor impairment differences were not explained by use of other substances and were unrelated to length of abstinence or lifetime number of MDMA doses. Findings provide limited evidence for neuropsychological differences between MDMA+ and MDMA- participants with the exception of motor impairments observed in the MDMA+ group. However, replication of this finding in a larger sample is warranted.

  18. Efficient Hyperelastic Regularization for Registration

    Darkner, Sune; Hansen, Michael Sass; Larsen, Rasmus;


    For most image registration problems a smooth one-to-one mapping is desirable, a diffeomorphism. This can be obtained using priors such as volume preservation, certain kinds of elasticity or both. The key principle is to regularize the strain of the deformation which can be done through penalizat......For most image registration problems a smooth one-to-one mapping is desirable, a diffeomorphism. This can be obtained using priors such as volume preservation, certain kinds of elasticity or both. The key principle is to regularize the strain of the deformation which can be done through...... penalization of the eigen values of the stress tensor. We present a computational framework for regularization of image registration for isotropic hyper elasticity. We formulate an efficient and parallel scheme for computing the principal stain based for a given parameterization by decomposing the left Cauchy...

  19. Regular algebra and finite machines

    Conway, John Horton


    World-famous mathematician John H. Conway based this classic text on a 1966 course he taught at Cambridge University. Geared toward graduate students of mathematics, it will also prove a valuable guide to researchers and professional mathematicians.His topics cover Moore's theory of experiments, Kleene's theory of regular events and expressions, Kleene algebras, the differential calculus of events, factors and the factor matrix, and the theory of operators. Additional subjects include event classes and operator classes, some regulator algebras, context-free languages, communicative regular alg

  20. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

    Leor eRoseman


    Full Text Available Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC between a standard template of different independent components analysis (ICA-derived resting state networks (RSNs under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.

  1. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers.

    Roseman, Leor; Leech, Robert; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L


    Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.

  2. Relevancia del género y de algunos polimorfismos genéticos en los efectos agudos y la farmacocinética de la ±3,4-metilendioximetanfetamina (mdma, “éxtasis”) en humanos

    Pardo Lozano, Ricardo


    El psicoestimulante sintético “éxtasis” (±3,4-metilendioximetanfetamina, MDMA) es la tercera droga de abuso más consumida en el mundo. La MDMA actúa como agonista indirecto de la serotonina y dopamina al invertir la acción de los transportadores de serotonina (5-HTT) y dopamina, e inhibe el citocromo P450 2D6 (CYP2D6) de forma casi-irreversible. Se ha sugerido que las mujeres son más sensibles que los hombres a los efectos subjetivos de la MDMA, principalmente los negativos. Sin embargo, no h...

  3. Environmental concentrations of 3,4-methylenedioxymethamphetamine (MDMA)-induced cellular stress and modulated antioxidant enzyme activity in the zebra mussel.

    Parolini, Marco; Magni, Stefano; Binelli, Andrea


    Recent monitoring studies showed measurable levels of the 3,4-methylenedioxymethamphetamine (MDMA) in aquatic environments. However, no information is currently available on its potential hazard to aquatic non-target organisms. The aim of this study was to investigate the potential sub-lethal effects induced by 14-day exposures to low MDMA concentrations (0.05 and 0.5 μg/L) to zebra mussel (Dreissena polymorpha) specimens through the application of a biomarker suite. The trypan blue exclusion method and the neutral red retention assay (NRRA) were used to assess MDMA cytotoxicity. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST), as well as the lipid peroxidation (LPO) and protein carbonyl content (PCC), were measured as oxidative stress indexes. The single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay, and the micronucleus test (MN test) were applied to investigate DNA damage, while filtration rate was measured as physiological parameter. Despite significant decrease in lysosome membrane stability, hemocyte viability and imbalances in CAT and GST activities pointed out at the end of the exposure to 0.5 μg/L, no significant variations for the other end points were noticed at both the treatments, suggesting that environmentally relevant MDMA concentrations did not induce deleterious effects to the zebra mussel.

  4. Regularized Statistical Analysis of Anatomy

    Sjöstrand, Karl


    This thesis presents the application and development of regularized methods for the statistical analysis of anatomical structures. Focus is on structure-function relationships in the human brain, such as the connection between early onset of Alzheimer’s disease and shape changes of the corpus cal...

  5. Regularization in Matrix Relevance Learning

    Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael


    A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can displa

  6. Singularities of slice regular functions

    Stoppato, Caterina


    Beginning in 2006, G. Gentili and D.C. Struppa developed a theory of regular quaternionic functions with properties that recall classical results in complex analysis. For instance, in each Euclidean ball centered at 0 the set of regular functions coincides with that of quaternionic power series converging in the same ball. In 2009 the author proposed a classification of singularities of regular functions as removable, essential or as poles and studied poles by constructing the ring of quotients. In that article, not only the statements, but also the proving techniques were confined to the special case of balls centered at 0. In a subsequent paper, F. Colombo, G. Gentili, I. Sabadini and D.C. Struppa (2009) identified a larger class of domains, on which the theory of regular functions is natural and not limited to quaternionic power series. The present article studies singularities in this new context, beginning with the construction of the ring of quotients and of Laurent-type expansions at points other than ...

  7. Regular inference as vertex coloring

    Costa Florêncio, C.; Verwer, S.


    This paper is concerned with the problem of supervised learning of deterministic finite state automata, in the technical sense of identification in the limit from complete data, by finding a minimal DFA consistent with the data (regular inference). We solve this problem by translating it in its enti

  8. Regularized Generalized Structured Component Analysis

    Hwang, Heungsun


    Generalized structured component analysis (GSCA) has been proposed as a component-based approach to structural equation modeling. In practice, GSCA may suffer from multi-collinearity, i.e., high correlations among exogenous variables. GSCA has yet no remedy for this problem. Thus, a regularized extension of GSCA is proposed that integrates a ridge…

  9. Regular inference as vertex coloring

    Costa Florêncio, C.; Verwer, S.


    This paper is concerned with the problem of supervised learning of deterministic finite state automata, in the technical sense of identification in the limit from complete data, by finding a minimal DFA consistent with the data (regular inference). We solve this problem by translating it in its

  10. 76 FR 3629 - Regular Meeting


    ... meeting of the Board will be held at the offices of the Farm Credit Administration in McLean, Virginia, on...Lean, Virginia 22102. SUPPLEMENTARY INFORMATION: This meeting of the Board will be open to the ] public... CORPORATION Farm Credit System Insurance Corporation Board Regular Meeting SUMMARY: Notice is hereby given of...

  11. Sean Leneghan, The Varieties of Ecstasy Experience: An Exploration of Person, Mind and Body in Sydney’s Club Culture (Saarbrücken: Lambert Academic Publishing, 2011

    Adam Langridge


    Full Text Available A review of the book: The Varieties of Ecstasy Experience: An Exploration of Person, Mind and Body in Sydney’s Club Culture, by Sean Leneghan. Lambert Academic Publishing: Saarbrücken, Germany, 2011. ISBN: 978-3-8454-1634-2. 286 pp. (Paperback $112 U.S.

  12. Assessment of cognitive brain function in ecstasy users and contributions of other drugs of abuse : Results from an fMRI study

    Jager, Gerry; de Win, Maartje M. L.; van der Tweel, Ingeborg; Schilt, Thelma; Kahn, Rene S.; van den Brink, Wim; van Ree, Jan M.; Ramsey, Nick F.


    Heavy ecstasy use has been associated with neurocognitive deficits in various behavioral and brain imaging studies. However, this association is not conclusive owing to the unavoidable confounding factor of polysubstance use. The present study, as part of the Netherlands XTC Toxicity study, investig

  13. Recursively-regular subdivisions and applications

    Rafel Jaume


    Full Text Available We generalize regular subdivisions (polyhedral complexes resulting from the projection of the lower faces of a polyhedron introducing the class of recursively-regular subdivisions. Informally speaking, a recursively-regular subdivision is a subdivision that can be obtained by splitting some faces of a regular subdivision by other regular subdivisions (and continue recursively. We also define the finest regular coarsening and the regularity tree of a polyhedral complex. We prove that recursively-regular subdivisions are not necessarily connected by flips and that they are acyclic with respect to the in-front relation. We show that the finest regular coarsening of a subdivision can be efficiently computed, and that whether a subdivision is recursively regular can be efficiently decided. As an application, we also extend a theorem known since 1981 on illuminating space by cones and present connections of recursive regularity to tensegrity theory and graph-embedding problems.     

  14. Thermal desorption counter-flow introduction atmospheric pressure chemical ionization for direct mass spectrometry of ecstasy tablets.

    Inoue, Hiroyuki; Hashimoto, Hiroaki; Watanabe, Susumu; Iwata, Yuko T; Kanamori, Tatsuyuki; Miyaguchi, Hajime; Tsujikawa, Kenji; Kuwayama, Kenji; Tachi, Noriyuki; Uetake, Naohito


    A novel approach to the analysis of ecstasy tablets by direct mass spectrometry coupled with thermal desorption (TD) and counter-flow introduction atmospheric pressure chemical ionization (CFI-APCI) is described. Analytes were thermally desorbed with a metal block heater and introduced to a CFI-APCI source with ambient air by a diaphragm pump. Water in the air was sufficient to act as the reactive reagent responsible for the generation of ions in the positive corona discharge. TD-CFI-APCI required neither a nebulizing gas nor solvent flow and the accompanying laborious optimizations. Ions generated were sent in the direction opposite to the air flow by an electric field and introduced into an ion trap mass spectrometer. The major ions corresponding to the protonated molecules ([M + H](+)) were observed with several fragment ions in full scan mass spectrometry (MS) mode. Collision-induced dissociation of protonated molecules gave characteristic product-ion mass spectra and provided identification of the analytes within 5 s. The method required neither sample pretreatment nor a chromatographic separation step. The effectiveness of the combination of TD and CFI-APCI was demonstrated by application to the direct mass spectrometric analysis of ecstasy tablets and legal pharmaceutical products.

  15. Long-term neurobiological consequences of ecstasy : A role for pre-existing trait-like differences in brain monoaminergic functioning?

    Wallinga, Alinde E.; de Boer, Sietse F.; Granneman, Ramon A.; Koolhaas, Jaap M.; Buwalda, Bauke


    This study investigated whether trait-like differences in brain monoaminergic functioning relate to differential vulnerability for the long-term neurochemical depletion effects of MDMA. Genetically selected aggressive (SAL) and non-aggressive (LAL) house-mice differing in baseline serotonergic and d

  16. General inverse problems for regular variation

    Damek, Ewa; Mikosch, Thomas Valentin; Rosinski, Jan


    Regular variation of distributional tails is known to be preserved by various linear transformations of some random structures. An inverse problem for regular variation aims at understanding whether the regular variation of a transformed random object is caused by regular variation of components ...

  17. Regular Motions of Resonant Asteroids

    Ferraz-Mello, S.


    RESUMEN. Se revisan resultados analiticos relativos a soluciones regulares del problema asteroidal eliptico promediados en la vecindad de una resonancia con jupiten Mencionamos Ia ley de estructura para libradores de alta excentricidad, la estabilidad de los centros de liberaci6n, las perturbaciones forzadas por la excentricidad de jupiter y las 6rbitas de corotaci6n. ABSTRAC This paper reviews analytical results concerning the regular solutions of the elliptic asteroidal problem averaged in the neighbourhood of a resonance with jupiter. We mention the law of structure for high-eccentricity librators, the stability of the libration centers, the perturbations forced by the eccentricity ofjupiter and the corotation orbits. Key words: ASThROIDS

  18. Energy functions for regularization algorithms

    Delingette, H.; Hebert, M.; Ikeuchi, K.


    Regularization techniques are widely used for inverse problem solving in computer vision such as surface reconstruction, edge detection, or optical flow estimation. Energy functions used for regularization algorithms measure how smooth a curve or surface is, and to render acceptable solutions these energies must verify certain properties such as invariance with Euclidean transformations or invariance with parameterization. The notion of smoothness energy is extended here to the notion of a differential stabilizer, and it is shown that to void the systematic underestimation of undercurvature for planar curve fitting, it is necessary that circles be the curves of maximum smoothness. A set of stabilizers is proposed that meet this condition as well as invariance with rotation and parameterization.

  19. Physical model of dimensional regularization

    Schonfeld, Jonathan F.


    We explicitly construct fractals of dimension 4-ε on which dimensional regularization approximates scalar-field-only quantum-field theory amplitudes. The construction does not require fractals to be Lorentz-invariant in any sense, and we argue that there probably is no Lorentz-invariant fractal of dimension greater than 2. We derive dimensional regularization's power-law screening first for fractals obtained by removing voids from 3-dimensional Euclidean space. The derivation applies techniques from elementary dielectric theory. Surprisingly, fractal geometry by itself does not guarantee the appropriate power-law behavior; boundary conditions at fractal voids also play an important role. We then extend the derivation to 4-dimensional Minkowski space. We comment on generalization to non-scalar fields, and speculate about implications for quantum gravity. (orig.)

  20. Maximum mutual information regularized classification

    Wang, Jim Jing-Yan


    In this paper, a novel pattern classification approach is proposed by regularizing the classifier learning to maximize mutual information between the classification response and the true class label. We argue that, with the learned classifier, the uncertainty of the true class label of a data sample should be reduced by knowing its classification response as much as possible. The reduced uncertainty is measured by the mutual information between the classification response and the true class label. To this end, when learning a linear classifier, we propose to maximize the mutual information between classification responses and true class labels of training samples, besides minimizing the classification error and reducing the classifier complexity. An objective function is constructed by modeling mutual information with entropy estimation, and it is optimized by a gradient descend method in an iterative algorithm. Experiments on two real world pattern classification problems show the significant improvements achieved by maximum mutual information regularization.