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MDMA
Terms modified by MDMA Selected AbstractsLegal piperazine-containing party pills-a new trend in substance misuseDRUG AND ALCOHOL REVIEW, Issue 3 2007JANIE SHERIDAN In this Harm Reduction Digest Sheridan, Butler, Wilkins and Russell address the emergent phenomenon of so-called ,legal party pills' which have become a significant drug issue in New Zealand and elsewhere. Although banned in a number of countries, they are currently legally available in New Zealand where they are marketed as ,safe' alternatives' to ,illicit' drugs often used in the dance scene such as MDMA and amphetamines. The authors describe the availability and use of these substances in New Zealand, summarize what is known about their effects, and speculate on harm reduction interventions and mechanisms of control and their possible sequelae. The paper provides a timely account of an emerging drug issue of relevance to harm reduction internationally. [source] MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical researchDRUG AND ALCOHOL REVIEW, Issue 1 2007KELLY J. CLEMENS Abstract The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') and methamphetamine (METH, ,ice', ,speed') are increasingly popular drugs amongst party-drug users. Studies with humans have investigated the acute and possible long-term adverse effects of these drugs, yet outcomes of such studies are often ambiguous due to a variety of confounding factors. Studies employing animal models have value in determining the acute and long-term effects of MDMA and METH on brain and behaviour. Self-administration studies show that intravenous METH is a particularly potent reinforcer in rats and other species. In contrast, MDMA appears to have powerful effects in enhancing social behaviour in laboratory animals. Brief exposure to MDMA or METH may produce long-term reductions in dopamine, serotonin and noradrenaline in the brain and alterations in the density of various receptor and transporter proteins. However it is still unclear, particularly in the case of MDMA, whether this reflects a ,neurotoxic' effect of the drug. Lasting alterations in social behaviour, anxiety, depressive symptoms and memory have been demonstrated in laboratory rats given MDMA or METH and this matches long-term changes reported in some human studies. Recent laboratory studies suggest that MDMA/METH combinations may produce greater adverse neurochemical and behavioural effects than either drug alone. This is of some concern given recent evidence that party drug users may be frequently exposed to this combination of drugs. [source] Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issuesDRUG AND ALCOHOL REVIEW, Issue 3 2006MICHAEL LYVERS Abstract The controversy over possible MDMA-induced serotonergic neurotoxicity in human recreational ecstasy users is examined critically in light of recent research findings. Although the designs of such studies have improved considerably since the 1990s, the evidence to date remains equivocal for a number of reasons, including (1) inconsistent findings on the existence and reversibility of persistent ecstasy-related serotonergic and cognitive deficits; (2) lack of clear association between changes in brain imaging measures and functional deficits attributed to MDMA-induced neurotoxicity; (3) the contribution of concomitant cannabis or other drug use to both brain imaging abnormalities and cognitive deficits; (4) methodological shortcomings such as failure to adequately match samples of ecstasy users and controls; (5) the questionable relevance of animal models of MDMA-induced neurotoxicity to typical human patterns of ecstasy use; and (6) the potential role of inherent pre-drug deficits in serotonergic systems, impulse control and executive cognitive function that may predispose to excessive use of drugs including ecstasy. Given the retrospective nature of nearly all studies of ecstasy users to date, the controversy over whether MDMA has ever caused neurotoxicity or cognitive deficit in human ecstasy users is likely to continue for some time without resolution. [source] Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. ShulginADDICTION, Issue 8 2010Udo Benzenhöfer ABSTRACT Aims Alexander T. Shulgin is widely thought of as the ,father' of +/,3,4-methylenedioxymethamphetamine (MDMA). This paper re-assesses his role in the modern history of this drug. Methods We analysed systematically Shulgin's original publications on MDMA, his publications on the history of MDMA and his laboratory notebook. Results According to Shulgin's book PIHKAL (1991), he synthesized MDMA in 1965, but did not try it. In the 1960s Shulgin also synthesized MDMA-related compounds such as 3,4-methylenedioxyamphetamine (MDA), 3-methoxy-4,5-methylenedioxyamphetamine (MMDA) and 3,4-methylenedioxyethylamphetamine (MDE), but this had no impact on his rediscovery of MDMA. In the mid-1970s Shulgin learned of a ,special effect' caused by MDMA, whereupon he re-synthesized it and tried it himself in September 1976, as confirmed by his laboratory notebook. In 1977 he gave MDMA to Leo Zeff PhD, who used it as an adjunct to psychotherapy and introduced it to other psychotherapists. Conclusion Shulgin was not the first to synthesize MDMA, but he played an important role in its history. It seems plausible that he was so impressed by its effects that he introduced it to psychotherapist Zeff in 1977. This, and the fact that in 1978 he published with David Nichols the first paper on the pharmacological action of MDMA in humans, explains why Shulgin is sometimes (erroneously) called the ,father' of MDMA. [source] Content of ecstasy in the Netherlands: 1993,2008ADDICTION, Issue 12 2009Neeltje Vogels ABSTRACT Aims The present paper outlines the results of analyses carried out on the content of tablets sold as ecstasy, collected in the Netherlands by the Drugs Information Monitoring System (DIMS) from January 1993 to December 2008. Methods During a period of 16 years, the DIMS analysed the content of 33 006 tablets sold as ecstasy that were handed in by numerous individual (potential) substance users. The DIMS results were compared with the results from various seized tablets to determine whether the DIMS is a monitor of the ecstasy consumer market. Results The DIMS system appears to be a market monitor that gives an accurate reflection of what is actually available on the hidden Dutch ecstasy market. During 16 years of monitoring, the purity [tablets containing only 3,4-methylenedioxymethamphetamine (MDMA)] was lowest around 1997. During this time-period many tablets contained other substances in addition to or instead of MDMA [e.g. 3,4-methylene-dioxyamphetamine (MDA), 3,4-methylene-dioxyethylamphetamine (MDEA) and N-methyl-a-(1,3-benzodixol-5-yl)-2-butamine (MBDB), amphetamine and caffeine]. From 1998 to 2008, the number of high-dose tablets (,106 mg MDMA per tablet) gradually increased. The same holds true for the proportion of tablets that contained only MDMA, reaching the highest levels in 2000 and 2004. After 2004, the purity of ecstasy tablets decreased again, caused mainly by a growing proportion of tablets containing meta-chlorophenylpiperazine (mCPP). Conclusions The DIMS results provide valuable qualitative information on the content of ecstasy tablets in the Netherlands, and its changes throughout the years. Moreover, the results were used for national and international risk assessments and important warning and prevention activities. [source] The Effects of Ecstasy (MDMA) on Rat Liver BioenergeticsACADEMIC EMERGENCY MEDICINE, Issue 7 2004Daniel E. Rusyniak MD Abstract Objectives: Use of the drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) can result in life-threatening hyperthermia. Agents that uncouple mitochondrial oxidative phosphorylation are known to cause severe hyperthermia. In the present study, the authors tested the hypothesis that MDMA directly uncouples oxidative phosphorylation in rat liver mitochondria. Methods: Effects on mitochondrial bioenergetics were assessed both in vitro and ex vivo. In vitro studies consisted of measuring the effects of MDMA (0.1,5.0 mmol/L) on states of respiration in isolated rat liver mitochondria and on mitochondrial membrane potential in a rat liver cell line. In ex vivo studies, mitochondrial rates of respiration were measured in the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously). Results: With the in vitro mitochondrial preparations, only concentrations of 5 mmol/L MDMA showed evidence of uncoupling with a slight increase in state 4 respiration and a corresponding decrease in the respiratory control index. MDMA (0.1,5.0 mmol/L) failed to decrease the mitochondrial membrane potential in 3,3-dihexyloxacarbocyanide iodide,stained WB-344 cells after either one or 24 hours of incubation. Ex vivo rates of respiration obtained from the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously) showed no evidence of mitochondrial uncoupling. Conclusions: These data suggest that while high concentrations of MDMA have some mild uncoupling effects in isolated mitochondria, these effects do not translate to cell culture or ex vivo studies in treated animals. These data do not support the view that the hyperthermia induced by MDMA is from a direct effect on mitochondrial oxidative phosphorylation. [source] The spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewaterADDICTION, Issue 11 2009Caleb J. Banta-Green ABSTRACT Aims To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse. Design and participants Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon. Measurements Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported. Findings The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas. Conclusion This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures. [source] Test,re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national studyADDICTION, Issue 10 2009Linda B. Cottler ABSTRACT Aims This study evaluated the prevalence and reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence with a purpose to determine whether it is best conceptualized within the category of hallucinogens, amphetamines or its own category. Design Test,re-test study. Participants MDMA users (life-time use >5 times) were recruited in St Louis, Miami and Sydney (n = 593). The median life-time MDMA consumption was 50 pills at the baseline. Measurements The computerized Substance Abuse Module for Club Drug (CD-SAM) was used to assess MDMA abuse and dependence. The Discrepancy Interview Protocol (DIP) was used to determine the reasons for the discrepant responses between the two interviews. Reliability of diagnoses, individual diagnostic criteria and withdrawal symptoms was examined using the kappa coefficient (,). Findings For baseline data, 15% and 59% met MDMA abuse and dependence, respectively. Substantial test,re-test reliability of the diagnoses was observed consistently across cities (, = 0.69). ,Continued use despite knowledge of physical/psychological problems' (87%) and ,withdrawal' (68%) were the two most prevalent dependence criteria. ,Physically hazardous use' was the most prevalent abuse criterion. Six dependence criteria and all abuse criteria were reported reliably across cities (,: 0.53,0.77). Seventeen of 19 withdrawal symptoms showed consistency in the reliability across cities. The most commonly reported reason for discrepant responses was ,interpretation of question changed'. Only a small proportion of the total discrepancies were attributed to lying or social desirability. Conclusion The adopted DSM-IV diagnostic classification for MDMA abuse and dependence was moderately reliable across cities. Findings on MDMA withdrawal support the argument that MDMA should be separated from other hallucinogens in DSM. [source] Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage?ADDICTION, Issue 3 2006E. Gouzoulis-Mayfrank ABSTRACT Background The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine: MDMA and some analogues) causes selective and persistent neurotoxic damage of central serotonergic neurones in laboratory animals. Serotonin plays a role in numerous functional systems in the central nervous system (CNS). Consequently, various abnormalities including psychiatric, vegetative, neuroendocrine and cognitive disorders could be expected in humans following MDMA-induced neurotoxic brain damage. Aims In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies with drug users. The aim of this paper was to review this literature and weigh the strength of the evidence for persistent brain damage in ecstasy users. Methods We used Medline to view all available publications on ,ecstasy' or ,MDMA'. All available studies dealing with ecstasy users entered this analysis. Findings and conclusions Despite large methodological problems the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial restitution 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, particularly memory, impairments with heavy ecstasy use. However, the evidence cannot be considered definite and the issues of possible pre-existing traits or the effects of polydrug use are not resolved. Recommendations Questions about the neurotoxic effects of ecstasy on the brain remain highly topical in light of its popularity among young people. More longitudinal and prospective studies are clearly needed in order to obtain a better understanding of the possible long-term sequelae of ecstasy use in humans. [source] PRECLINICAL STUDY: FULL ARTICLE: Tolerance to 3,4-methylenedioxymethamphetamine is associated with impaired serotonin releaseADDICTION BIOLOGY, Issue 3 2010Karen Jones ABSTRACT Tolerance to the behavioural effects of 3,4-methylenedioxymethamphetamine (MDMA) following high dose exposure has been attributed to alterations in serotonergic systems. The present study aimed to determine whether decreased 5-HT release and/or 5-HT2A/C receptor desensitization might play a role in tolerance by measuring the response to selective ligands following MDMA exposure. To this end, the latency to nose poke and emerge from a hide box to an open field arena following administration of various ligands to MDMA pre-treated and control rats was measured. Acute exposure to MDMA (0.0,3.3 mg/kg), the 5-HT releasing stimulant fenfluramine (0.0,2.0 mg/kg) and the 5-HT2 receptor agonist m-CPP (0.0,1.25 mg/kg) increased nose poke and emergence latency. Following administration of doses that produce 5-HT2A receptor-mediated behaviours, the 5-HT2 receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane failed to alter nose poke and emergence latency, suggesting a limited role of this receptor subtype in these behaviours. Activation of 5-HT2C receptors was implicated in the behavioural response to both MDMA and m-CPP since the increased emergence latency was dose-dependently attenuated by pre-treatment with the selective 5-HT2C receptor antagonist RS102221 (0.0,1.0 mg/kg). Tolerance to the behavioural effect of MDMA and fenfluramine but not m-CPP was produced by prior exposure to MDMA (10 mg/kg administered at two-hour intervals, total 40 mg/kg), and tissue levels of 5-HT and 5-HIAA were decreased. These findings suggest that tolerance to the increased nose poke and emergence latency produced by MDMA is due to impaired 5-HT release. [source] CLINICAL STUDY: BRIEF REPORT: Ecstasy (MDMA)-addicted subjects show increased serum levels of brain-derived neurotrophic factor, independently from a rise of drug-induced psychotic symptomsADDICTION BIOLOGY, Issue 3 2010Francesco Angelucci ABSTRACT The recreational drug ,ecstasy'[3,4-methylenedioxymethamphetamine (MDMA)] exerts a potent action on central serotonergic and dopaminergic neurons. These neurons utilize neurotrophins for their survival and function. In order to explore MDMA effects on neurotrophins, we measured by enzyme-linked immunosorbent assay the serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in ,ecstasy-addicted', ,ecstasy-addicted with signs of psychosis' and ,healthy' subjects. We found that BDNF serum levels were significantly increased in both groups of ,ecstasy-addicted' as compared with ,healthy subjects', supporting the hypothesis that BDNF is involved in MDMA action. [source] PRECLINICAL STUDY: Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chiralityADDICTION BIOLOGY, Issue 1 2010Nora Von Ameln ABSTRACT Despite the great popularity of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, not much is known about the detailed mechanisms of the acute and subchronic effects of the drug. There is especially a lack of information about the distinct behavioural effects of its optical isomers (enantiomers) R- and S-MDMA compared with the racemic RS-MDMA. For this purpose, adolescent rats were repetitively treated during two treatment stages (stage 1: days 1,10; stage 2: days 15, 17, 19) with RS-MDMA (5 or 10 mg/kg) or each of the respective enantiomers (5 mg/kg). The repeated treatment started on postnatal day (PND) 32 and locomotor activity was measured on each day by means of a photobeam-equipped activity box system. RS-MDMA or S-MDMA administration led acutely to massive hyperlocomotion and subchronically, to the development of behavioural sensitization after a short habituation period. R-MDMA was free of hyperactivating effects and even decreased locomotor behaviour upon repeated treatment. Nevertheless, co-administration of R-MDMA increased the hyperactivity of S-MDMA and made the S-MDMA induced behavioural sensitization state-dependent. The animals pre-treated with R-MDMA showed a sensitized response in adulthood when tested with RS-MDMA. Our results indicated that even in the absence of substantial neurotoxicity, both MDMA enantiomers can lead to long-term changes in brain circuitry and concomitant behavioural changes when repeatedly administered in adolescence. The sensitization development was most pronounced in the animals treated with S- and RS-MDMA; the animals with R-MDMA did not develop sensitization under repeated treatment but expressed a sensitized response when challenged with RS-MDMA. [source] BRIEF REPORT: Single exposure to cocaine or ecstasy induces DNA damage in brain and other organs of miceADDICTION BIOLOGY, Issue 1 2010Tathiana A. Alvarenga ABSTRACT We evaluated the overall genetic damage induced by different doses of cocaine and MDMA (3,4-Methylenedioxymethamphetamine) in several organs. One hour after intraperitoneal drug administration, mice were euthanized; peripheral blood, liver and brain were collected, and the cellular suspensions were used for the single cell gel (comet) assay. We determined that all doses of cocaine and MDMA tested were able to induce DNA damage in blood cells. Extensive genotoxic damage was induced by cocaine or MDMA at the highest doses used in liver cells. Brain cells were affected by all doses administrated. These findings demonstrate that cocaine and MDMA are potent genotoxins. [source] PRECLINICAL STUDY: Acquisition and reinstatement of MDMA-induced conditioned place preference in mice pre-treated with MDMA or cocaine during adolescenceADDICTION BIOLOGY, Issue 4 2009Manuel Daza-Losada ABSTRACT Those who take ecstasy are more likely to consume other drugs than non-users with cocaine abuse being reported by 75.5% of high school student MDMA (± 3,4-methylenedioxymetamphetamine hydrochloride) users. The aim of this work was to evaluate the effects of exposure during adolescence to MDMA, cocaine or to both drugs on the MDMA-induced conditioned place preference (CPP) in adult mice. Animals received two daily administrations of saline, 10 mg/kg of MDMA, 25 mg/kg of cocaine or 10 mg/kg of MDMA plus 25 mg/kg of cocaine over 3 days (from PD28 to 30). Three weeks after pre-treatment, the MDMA-induced CPP procedure was initiated (PD52). Acquisition of CPP was induced with a sub-threshold dose of MDMA (1.25 mg/kg) only in animals treated during adolescence with MDMA alone. Preference was established in all the groups after conditioning with 10 mg/kg of MDMA, while the time required to achieve extinction was longer in those pre-treated with cocaine or MDMA alone (46 and 28 sessions, respectively). Moreover, preference was reinstated with progressively lower priming doses of MDMA in mice pre-treated with MDMA or cocaine alone. These results demonstrate that early exposure to MDMA or cocaine induces long-lasting changes that last until adulthood and modify the response of animals to MDMA. [source] PRECLINICAL STUDY: Modulation of MDMA-induced behavioral and transcriptional effects by the delta opioid antagonist naltrindole in miceADDICTION BIOLOGY, Issue 3 2009Emilie Belkaï ABSTRACT The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only a few studies have focused on the possible interactions between the opioid system and the effects of 3,4-methylenedioxymethamphetamine (MDMA). In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference (CPP) were investigated in the presence of naltrindole (NTI), a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on pro-enkephalin (Penk) and pro-opiomelanocortin (Pomc) gene expression were assessed by real-time quantitative polymerase chain reaction (QPCR). The results showed that, after acute MDMA administration (9 mg/kg; i.p.), NTI (5 mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk gene expression was not modulated by acute MDMA, but a decrease of Pomc gene expression was observed, which was not antagonized by NTI. Administration of the antagonist prevented the acquisition of MDMA-induced CPP, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment, only the level of Pomc was modulated. The observed increase was totally blocked by NTI pre-treatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA. [source] PRECLINICAL STUDY: Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type AADDICTION BIOLOGY, Issue 2 2009Ema Alves ABSTRACT The administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ,ecstasy') to the rat results in mitochondrial oxidative damage in the central nervous system, namely lipid and protein oxidation and mitochondrial DNA deletions with subsequent impairment of the correspondent protein expression. Although these toxic effects were shown to be prevented by monoamine oxidase B inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated mitochondrial damage remains to be evaluated. Thus, the aim of the present study was to clarify the potential interference of a specific inhibition of MAO-A by clorgyline, on the deleterious effects produced by a binge administration of a neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations) to an adolescent rat model. The parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation and expression of the respiratory chain protein subunits II of reduced nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome oxidase (COXI). Considering that hyperthermia has been shown to contribute to the neurotoxic effects of MDMA, another objective of the present study was to evaluate the body temperature changes mediated by MDMA with a MAO-A selective inhibition by clorgyline. The obtained results demonstrated that the administration of a neurotoxic binge dose of MDMA to an adolescent rat model previously treated with the specific MAO-A inhibitor, clorgyline, resulted in synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, provoking high mortality. Inhibition of MAO-A by clorgyline administration had no protective effect on MDMA-induced alterations on brain mitochondria (increased lipid peroxidation, protein carbonylation and decrease in the expression of the respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced decrease in the expression of COXI. These results reinforce the notion that the concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the resulting severe synergic toxicity. [source] PRECLINICAL STUDY: Changes in leptin, ghrelin, growth hormone and neuropeptide-Y after an acute model of MDMA and methamphetamine exposure in ratsADDICTION BIOLOGY, Issue 1 2008Firas H. Kobeissy ABSTRACT Club drug abuse is a growing problem in the United States. Beyond addiction and toxicity are endocrine effects which are not well characterized. Specifically, the changes in appetite following exposure to drugs of abuse are an interesting but poorly understood phenomenon. Serum hormones such as leptin, ghrelin, growth hormone (GH), and neuropeptide-Y (NP-Y) are known to affect appetite, but have not been studied extensively with drugs of abuse. In this work, we examine the effects of club drugs 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) and methamphetamine (METH) (doses of 5, 20 and 40 mg/kg) on serum concentrations of these hormones in adult male Sprague-Dawley rats 6, 12, 24 and 48 hours after drug administration. In a dose-dependent manner, MDMA was shown to cause transient significant decreases in serum leptin and GH followed by a base line recovery after 24 hours. Conversely, serum ghrelin increased and normalized after 24 hours. Interestingly, serum NP-Y showed a steady decrease in both treatment of MDMA and METH at different time points and dosages. In humans, abuse of these drugs reduces eating. As evident from these data, acute administration of METH and MDMA had significant effects on different serum hormone levels involved in appetite regulation. Future studies should be performed to see how chronic, low dose drug administration would affect hormone levels and try to answer questions about the physiological mechanisms involved in the anorexic paradigm observed in drug use. [source] Methylone and mCPP, two new drugs of abuse?ADDICTION BIOLOGY, Issue 4 2005M. Bossong Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called ,Explosion'. mCPP (meta-chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded. [source] Effects of MPEP on expression of food-, MDMA- or amphetamine-conditioned place preference in ratsADDICTION BIOLOGY, Issue 3 2005Volker Herzig Recent studies have revealed the effectiveness of 2-methyl-6-(phenylethynyl)pyridine (MPEP), a highly selective antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), in conditioned drug reward. In a previous study we showed that MPEP blocks expression of context-conditioned morphine- but not cocaine reward in the rat. The present study now examines the effectiveness of MPEP in the expression of context-conditioned food, MDMA (,ecstasy?) or amphetamine reward. Therefore, three groups of rats were conditioned either to food, MDMA or amphetamine in the conditioned place preference (CPP) paradigm. After conditioning, CPP expression and locomotion were determined simultaneously in the presence and absence of the respective reward (i.e. food or drug), or after application of 50?mg/kg MPEP (the dose that was most effective in reducing morphine CPP expression in our previous study). As a result, MPEP reduced locomotion in all groups. Furthermore, only expression of amphetamine CPP was inhibited by MPEP, while expression of food and MDMA CPP was not affected, suggesting that the MPEP-induced inhibition of amphetamine CPP expression was not causally linked to the reduction of locomotion. Overall, we conclude that MPEP reduces expression of context-conditioned amphetamine but not MDMA or food reward. [source] N -methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB): its properties and possible risksADDICTION BIOLOGY, Issue 3 2000L. A. G. J. M. Van Aerts MBDB (N -methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane) is the ,-ethyl homologue of MDMA (3,4-methylenedioxy-N-methylamphetamine). MBDB is metabolized and excreted similarly to MDMA: presumably, the majority of oral MBDB is excreted in urine unmetabolized. The main metabolic routes in man are thought to be O-dealkylation and subsequent methylation, sulphation and glucuronidation of the newly formed hydroxy groups. The major acute neuropharmacological effects of MBDB in the rat are an increase in serotonin release in the brain and an inhibition of serotonin and noradrenaline re-uptake. These effects compare well with those of MDMA, although the latter is more potent. MBDB may also slightly increase dopamine release and inhibit dopamine re-uptake, but to a lesser extent than MDMA. This is important, as dopamine release has been implicated in the reinforcing qualities of substances such as cocaine and amphetamine. The neuroendocrine effects of MBDB resemble those of MDMA. Both substances increase plasma ACTH, corticosterone, prolactin and renin. The neurophysiological effects of MBDB are characterized by a decrease in electrical activity throughout the brain, most notably in the alpha 2 and delta frequency bands. In contrast, hallucinogens increase the activity in the alpha 1 band, especially in the corpus striatum. In drug discrimination tests in the rat, MBDB, like MDMA, can be distinguished clearly from both stimulants and hallucinogens. The class of substances to which MBDB belongs may be named entactogens. MBDB dose-dependently increases locomotor activity and decreases exploratory behaviour in the rat and causes distress vocalization and wing extension in the newly hatched chicken. The rewarding properties of MBDB appear to be smaller than those of MDMA, as suggested by a 2.5 times weaker potency in the conditioned place preference test in rats. The main subjective effects of MBDB in man are a pleasant state of introspection, with greatly facilitated interpersonal communication and a pronounced sense of empathy and compassion between subjects. In this respect, MBDB again resembles MDMA. However, there are also differences. MBDB has a slower and more gentle onset of action than MDMA, produces less euphoria and has less stimulant properties. The few toxicological data available suggest that MBDB may cause serotonergic deficits in the brain, although the potency of MBDB to cause this neurotoxic effect is smaller than that of MDMA. Severe acute reactions in man as have been reported for MDMA have not been published for MBDB. The dependence potential of MBDB appears to be small, probably even smaller than that of MDMA. MBDB has been available at least since 1994 but its position on the synthetic drugs market is marginal. Subjective reports indicate that MBDB is less popular among users than MDMA. The reason may be that MBDB produces less euphoria than MDMA. Another possible explanation is that MBDB largely lacks the stimulant properties of MDMA. We calculated a margin of safety with a method similar to one used in the risk assessment of pharmaceuticals. The results suggest that MBDB is three times less likely to cause serotonergic brain deficits than MDMA. However, it should be noted that for both substances the margin of safety is less than one, indicating that the risk of neurotoxicity is not negligible. In animals, serotonergic brain deficits after exposure to MDMA have been linked to the degeneration of serotonergic nerve terminals. [source] MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter bindingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Susan Schenk Abstract 3,4-Methylenedioxymethamphetamine (MDMA) self-administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug-naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self-administration was measured during daily 6-h sessions. Dose,effect data were obtained for MDMA (0.25,1.0 mg/kg/infusion) self-administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter- or self-administered MDMA on [3H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self-administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self-administration during the 15-day test period. The percentage of rats that acquired MDMA self-administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self-administration, and cocaine self-administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self-administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter-administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long-term self-administration may lead to long-lasting deficits in serotonin neurotransmission. [source] Context-dependent behavioural and neuronal sensitization in striatum to MDMA (ecstasy) administration in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Kevin T. Ball Abstract To investigate the neuronal mechanisms underlying the behavioural alterations that accompany repeated exposure to MDMA (ecstasy), we recorded the activity of >,200 striatal units in response to multiple, intermittent, locomotor-activating doses (5.0 mg/kg) of MDMA. Rats were treated with once-daily injections of either saline or MDMA for 5 days when housed in their home cage, followed by a challenge injection 3,5 days later when housed in a recording chamber. Because contextual drug associations might be particularly important to the expression of behavioural sensitization to chronic MDMA, a separate group of rats received repeated injections of MDMA alternately in the recording chamber or home cage, according to the above timeline. A sensitized locomotor response was observed only in rats that had previously experienced MDMA in the context of the recording chamber, and only on the challenge day. These sensitized animals also showed a decreased basal firing rate in neurons that were subsequently excited by MDMA when compared with the same category of neurons earlier in the treatment regimen. This resulted in a greater percentage increase from the baseline firing rate on the challenge day compared with the first and fifth days of treatment, even though this trend was not evident with an analysis of absolute firing rate. These results strongly support a role for context in the expression of MDMA-induced locomotor sensitization, and implicate striatal involvement in the neurobehavioural changes associated with the repeated use of MDMA. [source] High-throughput behavioral phenotyping in the expanded panel of BXD recombinant inbred strainsGENES, BRAIN AND BEHAVIOR, Issue 2 2010V. M. Philip Genetic reference populations, particularly the BXD recombinant inbred (BXD RI) strains derived from C57BL/6J and DBA/2J mice, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and covariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict the occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic coregulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium (TMGC) have obtained phenotype data from over 250 measures related to multiple behavioral assays across several batteries: response to, and withdrawal from cocaine, 3,4-methylenedioxymethamphetamine; "ecstasy" (MDMA), morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity and sleep/wake cycles. All traits have been measured in both sexes in approximately 70 strains of the recently expanded panel of BXD RI strains. Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent (N = 37) BXD RI lines was performed. Primary data are publicly available for heritability, sex difference and genetic analyses using the MouseTrack database, and are also available in GeneNetwork.org for quantitative trait locus (QTL) detection and genetic analysis of gene expression. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits. [source] The neuropsychology of ecstasy (MDMA) use: a quantitative reviewHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2007Konstantine K. Zakzanis Abstract A growing number of empirical studies have found varying neuropsychological impairments associated with use of 3,4-methylenedioxymethamphetamine (MDMA) use. We set out to determine to what extent neuropsychological abilities are impaired in MDMA users. To do so, meta-analytical methods were used to determine the magnitude of neuropsychological impairment in MDMA users across pre-specified cognitive domains. We found that cognitive impairment secondary to recreational drug use may result in what might be described as small-to-medium effects across all cognitive domains with learning and memory being most impaired. We also found that total lifetime ingestion of MDMA appears to be negatively associated with performance on tasks ranging from attention and concentration to learning and memory. Implications and limitations of these findings are discussed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Visuo-spatial working memory deficits in current and former users of MDMA (,ecstasy')HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2005Michelle Wareing Abstract Verbal working memory and executive deficits have been observed in ecstasy users. The present study sought to establish whether these also extended to visuo-spatial working memory. Thirty-six current ecstasy users, 12 former users (abstinent for at least 6 months) and 31 individuals that had never used ecstasy were tested on a maintenance plus type visuo-spatial working memory task. The task required participants to recall a sequence of specially marked cells in a four-by-four matrix display while at the same time performing a concurrent visual judgement task. Both the current and former user groups registered impairments relative to nonusers. These remained significant following statistical controls for a range of potentially confounding variables including the use of various other drugs during the 3 months prior to testing. Users were unimpaired on a simple spatial span measure suggesting that the deficits observed reflected the executive aspects of the spatial working memory task. Also consistent with executive involvement, statistical controls for measures of verbal working memory performance (computation span) removed half of the ecstasy-related variance in spatial working memory. The possibility that the pattern of results obtained might reflect some general impairment in information processing efficiency is discussed. Copyright © 2005 John Wiley & Sons, Ltd. [source] Death rates from ecstasy (MDMA, MDA) and polydrug use in England and Wales 1996,2002HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2003F. Schifano Abstract The present study reports on all deaths related to taking ecstasy (alone, or in a polydrug combination) occurring in England and Wales in the time frame August 1996,April 2002. Data presented here are based on all information recorded in the National Programme on Substance Abuse Deaths (np-SAD) database. The np-SAD regularly receives all information on drug related deaths in addicts and non addicts from coroners. A total of 202 ecstasy-related fatalities occurred in the chosen time-frame, showing a steady increase in the number of deaths each year. The ratio male:female was 4:1 and 3 of 4 victims were younger than 29. In 17% of cases ecstasy was the sole drug implicated in death and in the remaining cases a number of other drugs (mostly alcohol, cocaine, amphetamines and opiates) have been found. According to toxicology results, MDMA accounted for 86% of cases and MDA for 13% of cases; single deaths were associated with MDEA and PMA. This is the largest sample of ecstasy related deaths so far; possible explanations are given for the observed steady increase in ecstasy-related deaths and a tentative ,rationale' for this polypharmacy combination is then proposed. Copyright © 2003 John Wiley & Sons, Ltd. [source] Investigating the potential neurotoxicity of Ecstasy (MDMA): an imaging approachHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2001Liesbeth Reneman Abstract Human users of 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') users may be at risk of developing MDMA-induced neuronal injury. Previously, no methods were available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivo neuroimaging tools has begun to provide insights into the effects of MDMA in the human brain. In this review, contributions of brain imaging studies on the potential neurotoxic effects of MDMA and functional consequences are highlighted. An overview is given of PET, SPECT and MR spectroscopy studies, most of which show evidence of neuronal injury in MDMA users. Different neuroimaging tools are discussed that have investigated potential functional consequences of MDMA-induced 5-HT neurotoxic lesions. Finally, the contribution of brain imaging in future studies is discussed, emphasising the crucial role it will play in our understanding of MDMA's short- and long-term effects in the human brain. Copyright © 2001 John Wiley & Sons, Ltd. [source] Which neuroreceptors mediate the subjective effects of MDMA in humans?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2001A summary of mechanistic studies Abstract In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D2 receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd. [source] Methylenedioxymethamphetamine (MDMA, ,Ecstasy'): a stressor on the immune systemIMMUNOLOGY, Issue 4 2004Thomas J. Connor Summary Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ,Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin (IL)-1,, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ,chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed. [source] Evidence for a hallucinogen dependence syndrome developing soon after onset of hallucinogen use during adolescenceINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2006A.L. Stone Abstract This study uses latent class methods and multiple regression to shed light on hypothesized hallucinogen dependence syndromes experienced by young people who have recently initiated hallucinogen use. It explores possible variation in risk. The study sample, identified within public-use data files of the 1999 National Household Survey on Drug Abuse (NHSDA), consists of 1186 recent-onset hallucinogen users, defined as having initiated hallucinogen use within 24 months of assessment (median elapsed time since onset of use ,12 to 13 months). The recent-onset users in this sample were age 12 to 21 at the time of assessment and were between the ages of 10 and 21 at the time of their first hallucinogen use. The NHSDA included items to assess seven clinical features often associated with hallucinogen dependence, which were used in latent class modelling. Latent class analysis, in conjunction with prior theory, supports a three-class solution, with 2% of recent-onset users in a class that resembles a hallucinogen dependence syndrome, whereas 88% expressed few or no clinical features of dependence. The remaining 10% may reflect users who are at risk for dependence or in an early stage of dependence. Results from latent class regressions indicate that susceptibility to rapid transition from first hallucinogen use to onset of this hallucinogen dependence syndrome might be influenced by hallucinogenic compounds taken (for example, estimated relative risk, RR = 2.4, 95% CI = 1.6, 7.6 for users of MDMA versus users of LSD). Excess risk of rapid transition did not appear to depend upon age, sex, or race/ethnicity. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||||||||