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Memory function loss http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids =12404540&dopt=Abstract Prospective memory, everyday cognitive failure and central executive function in recreational users of Ecstasy. Heffernan TM, Jarvis H, Rodgers J, Scholey AB, Ling J. Human Cognitive Neuroscience Unit, University of Northumbria, Newcastle upon Tyne NE1 8ST, UK. Chronic use of MDMA (3,4-methylenedioxymethamphetamine), or Ecstasy, is believed to lead to impaired psychological performance, including well-documented decrements in laboratory and field tests of retrospective memory. Less is known about the impact of Ecstasy on aspects of 'everyday' memory, despite obvious concerns about such effects. The three studies reported here focused on the impact of chronic Ecstasy use on prospective memory (PM), associated central executive function and other aspects of day-to-day cognition. In study 1 46 regular Ecstasy users were compared with 46 Ecstasy-free controls using the Prospective Memory Questionnaire (PMQ). Ecstasy users reported significantly more errors in PM (remembering to do something in the future); these findings persisted after controlling for other drug use and the number of strategies used to aid memory. No difference was found between representative subgroups on the Lies Scale of the Eysenck Personality Questionnaire. In study 2 a different group of 30 regular Ecstasy users and 37 Ecstasy-free controls was assessed on the PMQ and on a central executive task comprising verbal fluency measures. The results confirmed the significant impairments in long- and short-term PM and revealed corresponding impairments in verbal fluency. In study 3 15 Ecstasy users, 15 cannabis users and 15 non-drug users were assessed using the Cognitive Failures Questionnaire, which requires participants to provide ratings of the frequency of various day-to-day cognitive slips. The results indicate that the Ecstasy users did not perceive their general cognitive performance to be worse than that of controls. Taken together, these results suggest that Ecstasy users have impaired PM that cannot be explained by an increased propensity to exaggerate cognitive failures. These may be attributable, in part, to central executive deficits that are due to frontal lobe damage associated with Ecstasy use. Copyright 2001 John Wiley & Sons, Ltd. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve& db=PubMed&list_uids=12379310&dopt=Abstract : Biochim Biophys Acta 2002 Oct 9;1588(1):26-32 Related Articles, Links 3,4-Methylenedioxymethamphetamine ("Ecstasy") induces apoptosis of cultured rat liver cells. Montiel-Duarte C, Varela-Rey M, Oses-Prieto JA, LopezZabalza MJ, Beitia G, Cenarruzabeitia E, Iraburu MJ. Department of Biochemistry, University of Navarra, Navarra, Pamplona, Spain. "Ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) has been shown to be hepatotoxic for human users, but molecular mechanisms involved in this effect remained poorly understood. MDMA-induced cell damage is related to programmed cell death in serotonergic and dopaminergic neurons. However, until now there has been no evidence of apoptosis induced by MDMA in liver cells. Here we demonstrate that exposure to MDMA caused apoptosis of freshly isolated rat hepatocytes and of a cell line of hepatic stellate cells (HSC), as shown by chromatin condensation of the nuclei and accumulation of oligonucleosomal fragments in the cytoplasm. In both cell types, apoptosis correlated with decreased levels of bcl-x(L), release of cytochrome c from the mitochondria and activation of caspase 3. In HSC, but not in hepatocytes, MDMA induced poly(ADP-ribose)polymerase (PARP) proteolysis. These results suggest that apoptosis of liver cells could be involved in the hepatotoxicity of MDMA. Hum Psychopharmacol 2001 Dec;16(8):557-577 Related Articles, Links http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd= Retrieve&db=PubMed&list_uids=12404536&dopt=Abs tract Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research. Parrott AC. Department of Psychology, University of East London, UK. MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' was scheduled as an illegal drug in 1986, but since then its recreational use has increased dramatically. This review covers 15 years of research into patterns of use, its acute psychological and physiological effects, and the long-term consequences of repeated use. MDMA is an indirect monoaminergic agonist, stimulating the release and inhibiting the reuptake of serotonin (5-HT) and, to a lesser extent, other neurotransmitters. Single doses of MDMA have been administered to human volunteers in double-blind placebocontrolled trials, although most findings are based upon recreational MDMA users. The 'massive' boost in neurotransmitter activity can generate intense feelings of elation and pleasure, also hyperactivity and hyperthermia. This psychophysiological arousal may be exacerbated by high ambient temperatures, overcrowding, prolonged dancing and other stimulant drugs. Occasionally the 'serotonin syndrome' reactions may prove fatal. In the days after Ecstasy use, around 80% of users report rebound depression and lethargy, due probably to monoaminergic depletion. Dosage escalation and chronic pharmacodynamic tolerance typically occur in regular users. Repeated doses of MDMA cause serotonergic neurotoxicity in laboratory animals, and there is extensive evidence for long-term neuropsychopharmacological damage in humans. Abstinent regular Ecstasy users often display reduced levels of 5-HT, 5-HIAA, tryptophan hydroxylase and serotonin transporter density; functional deficits in learning/memory, higher cognitive processing, sleep, appetite and psychiatric well-being, and, most paradoxically, 'loss of sexual interest/pleasure'. These psychobiological deficits are greatest in heavy Ecstasy users and may reflect serotonergic axonal loss in the higher brain regions, especially the frontal lobes, temporal lobes and hippocampus. These problems seem to remain long after the recreational use of Ecstasy has ceased, suggesting that the neuropharmacological damage may be permament. Copyright 2001 John Wiley & Sons, Ltd. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve& db=PubMed&list_uids=9039956&dopt=Abstract FASEB J 1997 Feb;11(2):141-6 Related Articles, Links The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells. Simantov R, Tauber M. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. The widely abused amphetamine analog 3,4methylenedioxymethamphetamine (MDMA, also called "ecstasy") induces hallucination and psychostimulation, as well as long-term neuropsychiatric behaviors such as panic and psychosis. In rodents and monkeys, MDMA is cytotoxic to serotonergic neurons, but this is less clear with humans. Herein, MDMA was cytotoxic to human serotonergic JAR cells; it altered the cell cycle, increased G2/M phase arrest, and induced DNA fragmentation in a cycloheximide-sensitive way. This apoptosis was not observed in nonserotonergic human NMB cells. The stereospecific effect of amphetamines in JAR cells, and the key role of NO and dopamine in MDMA-induced apoptosis were determined. The relevancy of MDMA-induced cell death to drug users is discussed. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve& db=PubMed&list_uids=12325046&dopt=Abstract 1: Synapse 2002 Dec;46(3):199-205 Related Articles, Links Validity of [123I]beta-CIT SPECT in detecting MDMAinduced serotonergic neurotoxicity. Reneman L, Booij J, Habraken JB, De Bruin K, Hatzidimitriou G, Den Heeten GJ, Ricaurte GA. Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. Recent [(123)I]beta-CIT single-photon emission computed tomography (SPECT) studies revealed decreased serotonin transporters (SERT) density in the brain of humans with a history of MDMA ("Ecstasy") use. However, [(123)I]beta-CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [(123)I]beta-CIT SPECT scans, a rhesus monkey was treated with MDMA (5 mg/kg, s.c. twice daily for 4 consecutive days). SPECT studies 4, 10, and 31 days after MDMA treatment revealed decreases in [(123)I]beta-CIT binding ratios in the SERT-rich brain region studied (hypothalamic/midbrain region), with SERT density reduced by 39% in this brain region 31 days after treatment. Data obtained with SPECT studies correlated well with SERT density determined with autoradiography after sacrifice of the animal (-34%). In addition, ex vivo [(123)I]betaCIT binding studies in rats 1 week after treatment with neurotoxic doses of MDMA (20 mg/kg s.c. twice daily for 4 consecutive days) revealed significant reductions in [(123)I]beta-CIT binding in SERT-rich regions (including the hypothalamus) when compared to saline-treated rats. The combined results of these studies indicate that SPECT imaging of SERT with [(123)I]beta-CIT can detect changes in SERT density secondary to MDMA-induced neurotoxicity in the hypothalamic/midbrain region, and possibly other brain http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve& db=PubMed&list_uids=12351788&dopt=Abstract Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ("Ecstasy") George A. Ricaurte,1* Jie Yuan,1 George Hatzidimitriou,1 Branden J. Cord,2 Una D. McCann3 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 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve& db=PubMed&list_uids=1347426&dopt=Abstract 1: Proc Natl Acad Sci U S A 1992 Mar 1;89(5):1817-21Related Articles, Links The molecular mechanism of "ecstasy" [3,4methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Rudnick G, Wall SC. Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510. MDMA ("ecstasy") has been widely reported as a drug of abuse and as a neurotoxin. This report describes the mechanism of MDMA action at serotonin transporters from plasma membranes and secretory vesicles. MDMA stimulates serotonin efflux from both types of membrane vesicle. In plasma membrane vesicles isolated from human platelets, MDMA inhibits serotonin transport and [3H]imipramine binding by direct interaction with the Na(+)dependent serotonin transporter. MDMA stimulates radiolabel efflux from plasma membrane vesicles preloaded with [3H]serotonin in a stereo-specific, Na(+)-dependent, and imipramine-sensitive manner characteristic of transporter-mediated exchange. In membrane vesicles isolated from bovine adrenal chromaffin granules, which contain the vesicular biogenic amine transporter, MDMA inhibits ATP-dependent [3H]serotonin accumulation and stimulates efflux of previously accumulated [3H]serotonin. Stimulation of vesicular [3H]serotonin efflux is due to dissipation of the transmembrane pH difference generated by ATP hydrolysis and to direct interaction with the vesicular amine transporter.