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General Discourse | Thread: Previous Forum index Next | |
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All 24 posts | Subject: 2 articles on MDMA pharmacology | Please login to post | Down | |
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pHarmacist (Hive Addict) 02-25-03 22:29 No 411595 
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2 articles on MDMA pharmacology (Rated as: excellent) |
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Synthesis and Neurotoxicological Evaluation of Putative Metabolites of the Serotonergic Neurotoxin 2-(Methylamino)-l-[3,4-(methylenedioxy)phenyl]propane [MDMA] Full-text: http://www.maps.org/publications/1992_zhao_1.pdf _________ ______ _____ ____ __ _ Are The "Entactogens" a Distinct Psychoactive Substance Class? The Contribution of Human Experimental Studies to the Classification of MDMA and Other Chemically Related Methylenedioxyamphetamine Derivatives Full-text: http://www.heffter.org/review/chapter6.pdf _________ ______ _____ ____ __ _ Accept No Imitations, There Can Only Bee One; www.the-hive.ws |
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pHarmacist (Hive Addict) 02-26-03 02:06 No 411709
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Scanned | ||||||
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I'm sorry for the bad layout of the first article due to the fact that it was scanned badly. I hope it's not a big problem.... Accept No Imitations, There Can Only Bee One; www.the-hive.ws |
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becomezen (Newbee) 02-26-03 19:04 No 411996 |
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great article ! | ||||||
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Pharm - great article , swim finds all that stuff interesting ,especially regarding metabolites and the clinical sessions of MDE that took place in switzerland (90% success rate , in a one year follow up study). I would like to request that you post links similar to this , if you were to have/find more . my guru once told me to "just be" , now I realize he meant "just bee" :) |
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Antoncho (Official Hive Translator) 02-27-03 05:30 No 412163 |
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Yes, i really enjoy that! | ||||||
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Dear pHarmacist, let me also thank you very much for this! It is a true pleasure. Things like that - where else you could've find them outside of obscure libraries? "...there can bee only one www.the-hive.ws"  Antoncho |
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pHarmacist (Hive Addict) 02-27-03 16:27 No 412278
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Another two, since the feedback was positive ;) | ||||||
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I'm very sorry if this has already been posted: Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Full-text: http://biology.uky.edu/Cooper/Class%20PDFs/parrott2.pdf _________ ______ _____ ____ __ _ And: _________ ______ _____ ____ __ _ Full-text: http://www.maps.org/dea-mdma/pdf/0008.PDF There can only bee one! Enjoy! Accept No Imitations, There Can Only Bee One; www.the-hive.ws |
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pHarmacist (Hive Addict) 03-01-03 02:22 No 412685
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MDMA/Booze (Alcohol) Combo Investigated: | ||||||
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3,4-Methylenedioxymethamphetamine (Ecstasy) and Alcohol Interactions in Humans: Psychomotor Performance, Subjective Effects, and Pharmacokinetics Full-Text: http://www.maps.org/publications/2002_hernandez-lopez_1.pdf Accept No Imitations, There Can Only Bee One; www.the-hive.ws |
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epistemologicide (Hive Addict) 03-01-03 02:55 No 412691 |
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great resource mate, im sending that stuff to... | ||||||
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great resource mate, im sending that stuff to my girl friend before its tool late for her, its too late for some, all those doing too much e should read this. FEAR MY GEAR i cook to save the planet!! http://www.counterorder.com/nihilism.html |
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pHarmacist (Hive Addict) 03-16-03 15:25 No 417592
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MDMA not as neurotoxic when administrated I.V? | ||||||
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Chem. Res. Toxicol., 14 (7), 863-870, 2001 Fengju Bai, Douglas C. Jones, Serrine S. Lau, and Terrence J. Monks* Center for Cellular and Molecular Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712-1074 Received January 16, 2001 Abstract: Reactive metabolites play an important role in 3,4-(±)-methylenedioxyamphetamine (MDA) and 3,4-(±)-methylenedioxymethamphetamine (MDMA; ecstasy)-mediated serotonergic neurotoxicity, although the specific identity of such metabolites remains unclear. 5-(Glutathion-S-yl)--methyldopamine (5-GSyl--MeDA) is a serotonergic neurotoxicant found in the bile of MDA-treated rats. The brain uptake of 5-GSyl--MeDA is decreased by glutathione (GSH), but sharply increases in animals pretreated with acivicin, an inhibitor of -glutamyl transpeptidase (-GT) suggesting competition between intact 5-GSyl--MeDA and GSH for the putative GSH transporter. -GT is enriched in blood-brain barrier endothelial cells and is the only enzyme known to cleave the -glutamyl bond of GSH. We now show that pretreatment of rats with acivicin (18 mg/kg, ip) inhibits brain microvessel endothelial -GT activity by 60%, and potentiates MDA- and MDMA-mediated depletions in serotonin (5-HT) and 5-hydroxylindole acidic acid (5-HIAA) concentrations in brain regions enriched in 5-HT nerve terminal axons (striatum, cortex, hippocampus, and hypothalamus). In addition, glial fibrillary acidic protein (GFAP) expression increases in the striatum of acivicin and MDA (10 mg/kg) treated rats, but remains unchanged in animals treated with just MDA (10 mg/kg). Inhibition of endothelial cell -GT at the blood-brain barrier likely enhances the uptake into brain of thioether metabolites of MDA and MDMA, such as 5-(glutathion-S-yl)--MeDA and 2,5-bis-(glutathion-S-yl)--MeDA, by increasing the pool of thioether conjugates available for uptake via the intact GSH transporter. The data indicate that thioether metabolites of MDA and MDMA contribute to the serotonergic neurotoxicity observed following peripheral administration of these drugs. ___________ ________ ____ _____ __ _ Full-text: http://pharmacist8.tripod.com/MDMA-tox.pdf Accept No Imitations, There Can Only Bee One; www.the-hive.ws |
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pHarmacist (Hive Addict) 03-23-03 13:44 No 420417
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Psychiatric disorders in Ecstasy (MDMA) users; (Rated as: good read) |
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...a literature review focusing on personal predisposition and drug history Human Psychopharmacology: Clinical and Experimental Volume: 16, Issue: 8, Date: December 2001, Pages: 641-645 K. Soar *, J. J. D. Turner, A. C. Parrott Department of Psychology, University of East London, London, UK Abstract: 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) has been implicated in the onset of a number of psychological disorders and associated with a number of psychiatric symptoms that have persisted after cessation of the drug. This paper is a review of the published psychiatric case studies from the last 10 years involving MDMA. Only 24% of patients had a previous psychiatric history and 34% had a psychiatric illness amongst first degree relatives. The percentage of patients not having had a personal or family history of psychiatric illness and the temporal relationship between MDMA ingestion and the experience of recurring symptoms strongly suggest a causal relationship between the drug and neuropsychiatric manifestations. Further supporting evidence comes from several studies using non-clinical samples. Ecstasy users that don't present themselves in healthcare settings as having clinical symptoms have significantly higher scores on certain subscales of the SCL-90 compared with Ecstasy-naive controls, with higher pathology scores in heavier Ecstasy users. The full-blown psychiatric cases may represent the broad end of this problematic spectrum. Copyright © 2001 John Wiley & Sons, Ltd. Full-text: http://pharmacist8.tripod.com/psych-dis-MDMA.pdf Accept No Imitations, There Can Only Bee One; www.the-hive.ws |
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Lego (Hive Bee) 11-04-03 14:29 No 468691 
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Ph.D. Thesis on MDMA&neurotoxicity (german) (Rated as: good read) |
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http://w210.ub.uni-tuebingen.de/dbt/volltexte/2002/605 Andreas Mayerhofer Acute and long-term effects of 3,4-methylendioxymethamphetamine (MDMA, 'ecstasy') on addiction and neurotoxicity in animal models Abstract: In this work, mechanisms of neurotoxicity and addiction of the designer drug MDMA ('Ecstasy') shall be further assessed by means of immunohistochemical, neurochemical and behavioural pharmacology methods in animal model of the rat. Acutely, MDMA leads to strong hyperactivity and stereotypies. Furthermore, MDMA reduced haloperidol-induced catalepsy. On cellular level, the hyperactivity correlated with strong overexpression of the inducible transcription factor c-Fos and of apoptosis-related proteins of the Bcl-family. In some brainareas a decreased number of Fos-positive nuclei was visible in the long term, which implicates a lower activity of mostly non-serotonergic neurons. Repeated treatment with MDMA lead to a serotonergic depletion, which was NA-independent. Temporarily, catecholaminergic neurons were also affected. The development of behavioural sensitization could also be shown. One important result of this work shows that an intact innervation of the forebrain by the locus coeruleus (LC) is essential for the development of behavioural sensitization. In the place-conditioning animal model could be shown that social isolation leads to a reinforcement of craving, robustness against extinction effects, and to increased relapse behaviour. Transferred to human, this means that the social environment gains much greater importance for the individual 'career of addiction'. In summary, MDMA may possess therapeutic potential for important medical indications, but at the same time it also shows a serious neurotoxic spectrum. Further intensive research on the mechanisms of MDMA action is necessary not only for the isolation of the therapeutically active components of the MDMA action, but also for the development of new strategies for prevention and therapy of MDMA-induced long term psychiatric damage. The candle that burns twice as bright burns half as long |
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Lego (Hive Bee) 05-01-04 21:10 No 504234
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Some more articles on MDMA (Rated as: excellent) |
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Altered states: the clinical effects of Ecstasy J.C. Cole, H.R. Sumnall Pharmacology & Therapeutics, 2003, 98, 35-58 DOI:10.1016/S0163-7258(03)00003-2 Abstract Ecstasy is the second most widely abused illegal drug in Europe. Ecstasy is the colloquial name for 3,4-methylenedioxymethamphetamine (MDMA), but not all Ecstasy tablets contain MDMA. When taken in hot, crowded environments, Ecstasy/MDMA users have developed acute complications that have had fatal consequences. Epidemiological evidence indicates that adverse reactions to Ecstasy/MDMA intoxication are rare and idiosyncratic. Potential mechanisms of action are reviewed. In animal studies, MDMA damages serotonergic fibres and reduces the number of serotonin transporter sites within the CNS. Demonstration of neurotoxicity in human users of Ecstasy is hampered by a number of confounds that the majority of published studies have failed to address. These confounds are reviewed and their impact is discussed. How strong is the evidence that brain serotonin neurons are damaged in human users of ecstasy? Stephen J. Kish Pharmacology, Biochemistry and Behavior, 2002, 71, 845-855 DOI:10.1016/S0091-3057(01)00708-0 Abstract Understanding the diverse functions of serotonin in the human brain can be obtained through examination of subjects having a lower than normal number of brain serotonin neurons. Behavioral abnormalities consistent with brain serotonergic damage have been reported in some polydrug users who also use the neurotoxin ecstasy (methylenedioxymethamphetamine, MDMA). This review evaluates the evidence from neuroimaging studies that brain serotonergic damage is a feature of human users of ecstasy. To date, neuroimaging studies designed to establish whether levels of brain serotonin neurons are lower than normal in ecstasy users have employed radioligands that bind to one component of the serotonin neuron, the serotonin transporter (SERT). Because these studies are methodologically flawed in terms of reliability or validity of the SERT measurement and appear to have employed polydrug users, no definitive information is yet available on the question of ecstasy toxicity to human brain serotonin neurons. Until these issue are resolved, it cannot be assumed that ecstasy exposure represents a chronic serotonin deficiency condition. Multiple molecular and neuropharmacological effects of MDMA (Ecstasy) Rabi Simantov Life Sciences, 2004, 74, 803-814 DOI:10.1016/j.lfs.2003.08.002 Abstract 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. The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) A. Richard Green, Annis O. Mechan, J. Martin Elliott, Esther O'Shea, M. Isabel Coldao Pharm. Rev., 2003, 55(3), 463-508 DOI:10.1124/pr.55.3.3. Abstract The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in priunaffected. In contrast, MDMA produces a selective longterm loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users. The tendency is to push it as far as you can |
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methyl_ethyl (Guardian) 05-02-04 01:00 No 504266 
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Full Text of Lego's Last Citation: | ||||||
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EDIT Oooops: I did not realize Lego posted the link for the full text, probably due to the recent search engine issues. I guess you can disregard the following text..... m_e Full Text of Lego's last citation available @ Post 459064 (methyl_ethyl: "The Pharmacology and Clinical Pharmacology of MDMA", General Discourse) This full text journal article is one of my top five entries regarding MDMA. It is quite comprehensive, and offers a wide spectra of information that can be utilized by almost anyone that has an interest in the pharmcology of MDMA. In short, there is something for everybody, MD's, PhD's, rPH's, PharmD's, Psychologists, Mental Health Clinicians, Ravers, Drug Addicts, E-Tards, Drug professionals, "NORML" civilians, club-goers, synthetic chemists, dj's, hive members, hive moderators, and even you....... great work y'all much_love methyl_ethyl Unipolar Mania, It's good for life... 
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methyl_ethyl (Guardian) 06-02-04 02:48 No 510822
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Chronic MDMA (ecstasy) use, cognition and mood (Rated as: excellent) |
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Chronic MDMA (ecstasy) use, cognition and mood K. McCardle, S. Luebbers, J. D. Carter, R. J. Croft, C. Stough Psychopharmacology (2004) 173: 434–439 DOI:10.1007/s00213-004-1791-0 Abstract Rationale: It has been suggested that 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) causes damage to the serotonergic system, and that this damage results in cognitive and mood impairments. Objectives: To examine the effect of chronic MDMA usage on a wide battery of cognitive tests and psychological abilities and processes. Methods: In the present study, the performance of 17 participants with a history of MDMA use was compared to the performance of 15 control subjects on a battery of neuropsychological tests. This battery included tests for depression, immediate word recall, delayed recall, attention and working memory. Results: Results indicated that the MDMA group had significantly higher scores for depression than the control group, and displayed poorer delayed recall and verbal learning than controls after accounting statistically for the effects of cannabis and depression. Conclusions: These results suggest that MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. Unipolar Mania, It's good for life...
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Rhodium (Chief Bee) 06-02-04 13:23 No 510942 
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Still no revelation | ||||||
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The study finds a correlation between MDMA use and lower scores on their test, but it fails to display any causality. It is not shown whether a depressive mood is a predictor of MDMA use or a result of it. The Hive - Clandestine Chemists Without Borders |
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7is (Hive Bee) 06-10-04 11:52 No 512572 
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More Psychopharmacology(Berl.) (Rated as: excellent) |
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New issue of Psychopharmacology(Berl.) was devoted to MDMA, methyl_ethyl already posted one article, I think these are the other interesting ones. MDMA: fact and fallacy, and the need to increase knowledge in both the scientific and popular press. Richard Green A. Psychopharmacology (Berl). 2004 May;173(3-4):231-3. Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice. Fantegrossi WE, Kiessel CL, Leach PT, Martin CV, Karabenick RL, Chen X, Ohizumi Y, Ullrich T, Rice KC, Woods JH. Psychopharmacology (Berl). 2004 May;173(3-4):270-7. RATIONALE. No selective antagonists for the effects of MDMA have yet been identified. The structurally-similar, naturally-occurring plant alkaloid nantenine (9,10-methylenedioxy-1,2 dimethoxyaporphine) may represent such a compound. OBJECTIVES. To investigate the capacity of nantenine to block and/or reverse MDMA-induced hyperthermia, lethality, locomotor stimulation, and head twitches in mice, and to compare these actions with those of the selective alpha(1) antagonist prazosin and the selective 5-HT(2A) antagonist M100907. METHODS. Pretreatments of either 10 mg/kg nantenine or 1 mg/kg prazosin were administered 15 min before 32 mg/kg MDMA; core temperature and locomotor stimulation were then monitored via radiotelemetry for at least 3 h. In further hyperthermia studies, 32 mg/kg MDMA was administered first and temperature was allowed to rise for 30 min; 10 mg/kg nantenine, 1 mg/kg prazosin, or 1 mg/kg M100907 was then administered in an attempt to reverse MDMA-induced hyperthermia. In lethality assays, percent lethality was quantified 2 h after MDMA injection in two distinct housing conditions, one or 12 mice per cage, with or without 15 min pretreatments of 10 mg/kg nantenine or 1 mg/kg prazosin. Drug elicited head twitches were quantified for 10 min following administration of either MDMA enantiomer, with and without pretreatments of 1 mg/kg nantenine, 0.1 mg/kg prazosin, or 0.001 mg/kg M100907. RESULTS. Nantenine blocked and rapidly reversed MDMA-induced hyperthermia, attenuated lethality in both housing conditions, and reduced MDMA-induced locomotor stimulation and head twitches in mice. Prazosin blocked, but did not reverse, MDMA-induced hyperthermia, attenuated lethality (more effectively in singly-housed animals), and reduced MDMA-induced locomotor stimulation and head twitches. M100907 did not reverse MDMA-induced hyperthermia, but effectively blocked drug-elicited head twitches. CONCLUSIONS. Nantenine functions as an effective antagonist against a wide range of MDMA-induced effects in mice. The antagonist actions of this compound at serotonin and adrenergic receptors may be differentially implicated across endpoints. Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics. Farre M, De La Torre R, O Mathuna B, Roset PN, Peiro AM, Torrens M, Ortuno J, Pujadas M, Cami J. Psychopharmacology (Berl). 2004 May;173(3-4):364-75. RATIONALE. 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is increasingly used by young people for its euphoric and empathic effects. MDMA presents non-linear pharmacokinetics, probably by inhibition of cytochrome P450 isoform 2D6. Users are known to often take more than one dose per session. This practice could have serious implications for the toxicity of MDMA. OBJECTIVE. To evaluate the pharmacological effects and pharmacokinetics of MDMA following the administration of two repeated doses of MDMA (24 h apart). METHODS. A randomised, double-blind, cross-over, placebo controlled trial was conducted in nine healthy male subjects. Variables included physiological, psychomotor performance, subjective effects, endocrine response and pharmacokinetics. MDMA 100 mg or placebo was administered in two successive doses separated by an interval of 24 h. RESULTS. MDMA produced the prototypical effects of the drug. Following a second dose, plasma concentrations of MDMA increased (AUC 77% and C(max) 29%) in comparison with the first. The increase is greater than those expected by simple accumulation and indicates metabolic inhibition. The pharmacological effects after the second dose were slightly higher than those observed after the first in the majority of variables including blood pressure, heart rate, most subjective effects and cortisol concentrations. The effects were similar in the case of pupil diameter, esophoria and prolactin. CONCLUSIONS. Pharmacological effects after the second administration were higher than those following the first but lower than expected. A disproportionate increase in plasma concentrations in MDMA and MDA was observed most likely due to metabolic inhibition. This inhibition lasts at least 24 h. Further experiments need to be conducted to evaluate its duration. Self-reported psychopathological symptoms in recreational ecstasy (MDMA) users are mainly associated with regular cannabis use: further evidence from a combined cross-sectional/longitudinal investigation. Daumann J, Hensen G, Thimm B, Rezk M, Till B, Gouzoulis-Mayfrank E. Psychopharmacology (Berl). 2004 May;173(3-4):398-404. RATIONALE. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) has become a widely used recreational drug among young people. This is of great concern, since MDMA is neurotoxic in animal studies and its use has been associated with psychological distress and a variety of self-reported psychiatric symptoms. However, exploring the origins of psychopathology in ecstasy users is hampered by the frequent polydrug use and by the cross-sectional design of all investigations, so far. OBJECTIVES. The present study combines a cross-sectional with a longitudinal approach to further clarify the impact of the use of other illicit drugs on psychopathological symptoms reported by ecstasy users. METHODS. At baseline, we administered self-rating scales for impulsivity, sensation seeking and general psychological complaints to 60 recreational ecstasy users and 30 matched controls. From the initial sample of ecstasy users, 38 subjects were re-examined 18 months later. RESULTS. At baseline, ecstasy users reported significantly more psychological complaints than controls. However, self-reported psychopathology was mainly associated with regular cannabis use. At follow-up, subjects who had abstained from ecstasy use during the follow-up period did not differ from those reporting continued consumption. In contrast, subjects with regular concomitant cannabis use during the follow-up period reported more anxiety, interpersonal sensitivity and obsessive-compulsive behaviour than cannabis-abstinent users. Finally, higher levels of obsessive-compulsive behaviour, interpersonal sensitivity, depression, anxiety, phobic anxiety and paranoid ideation were significantly correlated with the duration of regular interim cannabis use. CONCLUSIONS. The present findings suggest that self-reported psychopathology in ecstasy users is predominantly attributable to concomitant use of cannabis. Abstinence from cannabis and not ecstasy seems to be a reliable predictor for remission of psychological complaints in ecstasy users. A bitter pill. Overview of ecstasy (MDMA, MDA) related fatalities. Schifano F. Psychopharmacology (Berl). 2004 May;173(3-4):242-8. RATIONALE. The issue of ecstasy-related fatalities has extensively attracted the attention of both the media and the general public, but less so of the scientific literature. OBJECTIVES. The aim of the present review is to focus on the epidemiological, clinical and pharmacological issues related to ecstasy fatalities. RESULTS. Possibly due to a number of different reasons, the rates of ecstasy-related deaths seem to have peaked in recent years. MDMA metabolism is regulated by the levels of CYP2D6 and COMT (both exhibit some genetic polymorphism), and range of activity of these enzymes may account for some inter-individual differences in terms of toxic responses to the drug. A small increase in MDMA dosage can lead to a significant rise in drug plasma concentration. Due to their tolerance to MDMA psychoactive effects, some individuals may binge with dosages that may be the cause of serious concern. In experienced users, a reverse tolerance phenomenon can also be observed. Together with ecstasy, most of the misusers take a number of different compounds and the possible rationale of this style of consumption is commented upon here. Frequently, the lethal complications observed after acute MDMA administration can be the consequence of the occurrence of a serotonin syndrome and/or of sympathomimetic overstimulation (both conditions are exacerbated by environmentally induced overheating). CONCLUSIONS. A number of methodological problems can contribute to making difficult the interpretation of the role played by ecstasy in so-called ecstasy-related deaths, especially so if accurate information is not available. |
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jsorex (Hive Addict) 06-10-04 18:43 No 512615 
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Cannabis for ecstasy heads (Rated as: excellent) |
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Check this out: DOI:10.1016/j.neuropharm.2004.01.002 Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats Neuropharmacology Volume 46, Issue 7 , June 2004, Pages 954-965 Kirsten C. Morley, Kong M. Li, Glenn E. Hunt, Paul E. Mallet and Iain S. McGregor Abstract Cannabinoid¨CMDMA interactions were examined in male Wistar rats. MDMA (4¡Б5 mg/kg or 2¡Б10 mg/kg over 4 h on each of 2 days) was administered with or without ¦¤9-tetrahydrocannabinol (THC) (4¡Б2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2¡Б0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2¡Б5 mg/kg). Co-administered ¦¤9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered ¦¤9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered ¦¤9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered ¦¤9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors. Author Keywords: Author Keywords: MDMA; Ecstasy; Cannabinoid; Hyperthermia; Hypothermia; Neurotoxicity 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 José Francisco Navarroa, Alicia Riverab, Enrique Maldonadoa, María Cavasa and Adelaida de la Calleb Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 28, Issue 2 , March 2004, Pages 249-254 Abstract 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. 
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jsorex (Hive Addict) 06-11-04 22:11 No 512862
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Modern ecstasy use in practise (Rated as: excellent) |
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Also, imagine all these ectasy influenced ravers full of love being aproached by some folk asking for an oral fluid sample Estimating the prevalence of Ecstasy use among club rave attendees. Authors: Yacoubian Jr., George S. Deutsch, Julia K. Schumacher, Elizabeth J. Contemporary Drug Problems; Spring2004, Vol. 31 Issue 1, p163, 15p Abstract: The “rave” phenomenon has been a major element in the resurgence of psychedelic drug use in Western society. Purportedly central to raves is the use of “club drugs” such as 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”). To date, however, few studies have examined the prevalence of Ecstasy use and dependence symptoms among rave attendees in the United States. In the current study, self-report drug use information and oral fluid (OF) specimens were collected from a sample of adult “club rave” attendees along the Baltimore-Washington corridor between September and November 2002. Data collection was scheduled between 12 midnight and 5 a.m. Participation rates were high. Of the 192 rave attendees approached, 80% completed the interview. Of those who completed the interview. 82% provided an OF specimen. Twenty-four percent of the respondents with usable specimens (N=103) reported using Ecstasy within the two days preceding the interview, while 30% tested positive for MDMA by OF analysis. Sixteen percent responded affirmatively to at least one of the three dependence symptoms. Self-reported 12-month Ecstasy users were more likely than non-users to be white, and recent users were more likely to have used most other drugs of abuse during the 12 months preceding the interview. ISSN: 0091-4509
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methyl_ethyl (Guardian) 08-23-04 01:55 No 526882
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MDMA mediated production of H2O2 in vitro (Rated as: good read) |
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3,4-Methylenedioxymethamphetamine (MDMA, ecstasy)-mediated production of hydrogen peroxide in an in vitro model: the role of dopamine, the serotonin-reuptake transporter, and monoamine oxidase-B. Hrometz SL, Brown AW, Nichols DE, Sprague JE. Neurosci Lett. 2004 Aug 26;367(1):56-9. Medline (PMID=15308297) Abstract: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) has been shown to induce long-term deficits in serotonergic function in animal models. Several studies have suggested that dopamine (DA) uptake into serotonin (5-HT) terminals by the 5-HT reuptake transporter (SERT) and subsequent deamination by monoamine oxidase-B (MAO-B) leads to the formation of hydrogen peroxide and may be major contributors to this serotonergic toxicity. In the present study, when human choriocarcinoma (JAR) cells were exposed to MDMA (1.2mM) for 6h, followed by treatment with DA (0.1mM), hydrogen peroxide production increased over a 24h period, peaking at 420% over baseline and decreasing cell viability by 30%. DA alone increased hydrogen peroxide production 84% over baseline, but did not significantly decrease cell viability. Incubation of MDMA treated cells with the SERT inhibitor, fluoxetine (500nM) or the MAO-B inhibitor, l-deprenyl (0.1mM) for 30min prior to DA, significantly blocked free radical production and cell death. These findings support the hypothesis that the deamination of DA by MAO-B within the serotonergic cell can lead to hydrogen peroxide formation and ultimately cell death. regards, methyl_ethyl Unipolar Mania, It's good for life...
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merbst (Hive Bee) 08-23-04 19:19 No 526970 |
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Re: Human psychopharmacology of Ecstasy ... | ||||||
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scarmani (Hive Bee) 09-21-04 11:29 No 532483 
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Limitations of Scaling from Animals to Humans (Rated as: good read) |
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Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans. Rafael de la Torre and Magi Farre, Trends in Pharmacological Sciences. 25(10), 505-508 (2004) Abstract: Several studies suggest that MDMA-induced acute toxicity and long-term neurotoxicity is dependent on the metabolic disposition of MDMA. Differences in MDMA metabolism among animal species might therefore account for different sensitivities to its neurotoxic effects. The kinetic parameters of enzymes that regulate the formation of neurotoxic metabolites of MDMA differ among species, as does the ability of MDMA to self-inhibit these enzymes and the degree of genetic polymorphisms exhibited by these enzymes. Such features limit allometric scaling across animal models. boot from the shadow of a broken mirror |
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Rhodium (Chief Bee) 09-30-04 10:49 No 533892
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MDMA-mediated formation of H2O2 by MAO-B/DA (Rated as: good read) |
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3,4-Methylenedioxymethamphetamine (MDMA, ecstasy)-mediated production of hydrogen peroxide in an in vitro model: the role of dopamine, the serotonin-reuptake transporter, and monoamine oxidase-B Sandra L. Hrometz, Andrew W. Brown, David E. Nichols and Jon E. Sprague, Neuroscience Letters 367(1), 56-59 (2004) (Uploaded file not existing) Abstract 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) has been shown to induce long-term deficits in serotonergic function in animal models. Several studies have suggested that dopamine (DA) uptake into serotonin (5-HT) terminals by the 5-HT reuptake transporter (SERT) and subsequent deamination by monoamine oxidase-B (MAO-B) leads to the formation of hydrogen peroxide and may be major contributors to this serotonergic toxicity. In the present study, when human choriocarcinoma (JAR) cells were exposed to MDMA (1.2 mM) for 6 h, followed by treatment with DA (0.1 mM), hydrogen peroxide production increased over a 24 h period, peaking at 420% over baseline and decreasing cell viability by 30%. DA alone increased hydrogen peroxide production 84% over baseline, but did not significantly decrease cell viability. Incubation of MDMA treated cells with the SERT inhibitor, fluoxetine (500 nM) or the MAO-B inhibitor, L-deprenyl (0.1 mM) for 30 min prior to DA, significantly blocked free radical production and cell death. These findings support the hypothesis that the deamination of DA by MAO-B within the serotonergic cell can lead to hydrogen peroxide formation and ultimately cell death. The Hive - Clandestine Chemists Without Borders |
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methyl_ethyl (Guardian) 10-13-04 02:21 No 535601
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Selected Neuropsychobiology Articles (Rated as: excellent) |
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Edit: I had to edit the post in order to get rid of the nonsensical characters that carried over from the "cut and paste" from the online journal.  Is MDMA (Ecstasy) Neurotoxic in Humans? An Overview of Evidence and of Methodological Problems in Research H. Valerie Curran Neuropsychobiology 2000;42:34-41 DOI:10.1159/000026668 Abstract: Evidence from research with a range of animal species, from rodents to non-human primates, has shown that MDMA (3,4-methylenedioxymethamphetamine) is neurotoxic. This article explores the evidence that MDMA may be neurotoxic in humans by briefly overviewing three types of research: (1) neurobiological, (2) psychological/somatic and (3) psychiatric. The first type of evidence derives from neuropharmacological and neuroendocrine studies, the second type focuses on psychological function and somatic symptoms in MDMA users, and the third involves studies of psychiatric cases in people who have taken MDMA. Evidence from these types of studies is indirect and differs in the degree to which any causative links are implied between observed effects, MDMA use and human neurotoxicity. These issues are critically discussed within the context of the wide-ranging methodological problems in human research with MDMA. Is MDMA a Human Neurotoxin?: Diverse Views from the Discussants J.J.D. Turner A.C. Parrott Neuropsychobiology 2000;42:42-48 DOI:10.1159/000026669 Abstract: Every discussant at the Novartis symposium was invited to submit a 250-word abstract, giving their views upon the question: Is MDMA a human neurotoxin?. These abstracts are presented here. They illustrate a wide range of viewpoints and opinions, as might be expected from experts in such diverse fields: animal neuroscience, human cognitive testing, police pathology laboratory, psychotherapeutic institute and psychiatric hospital. Some abstracts emphasized the methodological weaknesses of the human empirical data: the uncertain nature of Ecstasy tablets, the reliance on self-report data, and the contributory factors of heat, dancing/exertion, poor diet and other illicit drugs. These factors may lead to psychobiological changes, which could be misinterpreted as neural damage. The absence of gliosis in animal models was also noted, which led to suggestions that there might be alternative interpretations for the neural changes which have been observed in rats and monkeys. Others noted the absence of neural/behavioural change following a single Ecstasy tablet, or commented upon the therapeutic benefits of MDMA in a quiet supportive environment. Nevertheless, novel studies from England, Germany, Italy, the Netherlands, Scotland and Wales confirmed and extended the range of cognitive, behavioural, EEG and neurological deficits, displayed by drugfree Ecstasy users. Moreover, these deficits often remained when other illicit drug use was statistically controlled. In conclusion: If MDMA neurotoxicity in humans is a myth, then it is a myth with a heavy serotonergic component. Human Research on MDMA (3,4-Methylenedioxymethamphetamine) Neurotoxicity: Cognitive and Behavioural Indices of Change A.C. Parrott Neuropsychobiology 2000;42:17-24 DOI:10.1159/000026666 Abstract: Laboratory animals can develop serotonergic neurotoxicity after repeated doses of 3,4-methylenedioxymethamphetamine (MDMA) or Ecstasy. If similar neural damage occurs in humans, this may be evident in cognitive or behavioural impairments. In a review of the behavioural skills shown by drug-free recreational Ecstasy users, three aspects of cognitive performance are often affected: reduced memory for new information (Rivermead Behavioral Memory, supraspan word recall), impaired higher executive processing (Wisconsin Card Sort, Tower of London), and heightened impulsivity (Impulsiveness, Venturesomeness and Empathy Questionnaire, Matching Familiar Figures test). Performance on other more basic cognitive functions is generally unimpaired (simple reaction time, choice reaction time, number vigilance, Stroop, trail making). Some Ecstasy users also complain of poor memories and/or concentration difficulties, which they attribute to MDMA use. There are many methodological problems and uncertainties with research in this field: non-random allocation of subjects to drug conditions, the deleterious effects of other psychoactive drugs, and the possibility that these adverse profiles reflect pre-existing personality characteristics in Ecstasy users. However, this particular pattern of cognitive decrements in humans, is consistent with the animal data on those brain areas showing serotonergic damage following MDMA: the frontal cortex (impulsivity and higher cognitive impairments), and hippocampus (memory deficits). Finally, this profile of cognitive deficits is also consistent with a hypothetical integrative construct: namely reduced cortical inhibition. (+3,4-Methylenedioxymethamphetamine (Ecstasy')-Induced Serotonin Neurotoxicity: Clinical Studies Una D. McCann, Victoria Eligulashvili, George A. Ricaurte Neuropsychobiology 2000;42:11-16 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a brain serotonergic neurotoxin in experimental animals, including nonhuman primates. It is also an increasingly popular recreational drug of abuse, and doses of MDMA that are used recreationally overlap with those that produce serotonin (5-HT) neurotoxicity in animals. Studies in human MDMA users probing for evidence of brain serotonergic neurotoxicity indicate that some MDMA users may incur MDMA-related 5-HT neural injury and, possibly, functional sequelae. In particular, MDMA users have selective decrements in cerebrospinal fluid 5-hydroxyindoleacetic acid and brain 5-HT transporters, similar to nonhuman primates with documented MDMA-induced neurotoxicity. Functional abnormalities seen in MDMA users that may be related to 5- HT injury include cognitive deficits, altered sleep architecture, altered neuroendocrine function, altered behavioralresponses to 5-HT selective drugs, and increased impulsivity. Additional studies in animals, as well as longitudinal and epidemiological studies in MDMA users, are required to confirm and extend the present data, and to determine whether MDMA users are at increased risk for developing neuropsychiatric illness as they age. I find the information to be slightly dated however informative none the less.... regards, methyl_ethyl Unipolar Mania, It's good for life...
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methyl_ethyl (Guardian) 10-20-04 01:23 No 536712
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MDMA: Loud Noise: Nigrostriatal Toxicity (Murine) (Rated as: good read) |
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Loud Noise Enhances Nigrostriatal Dopamine Toxicity Induced by MDMA in Mice MARCO GESI, MICHELA FERRUCCI, MARIO GIUSIANI, PAOLA LENZI, GLORIA LAZZERI, MARIA G. ALESSANDRI`, ALESSANDRA SALVADORINI, FEDERICA FULCERI, ANTONIO PELLEGRINI, FRANCESCO FORNAI, AND ANTONIO PAPARELLI. MICROSCOPY RESEARCH AND TECHNIQUE 64:297–303 (2004) DOI:10.1002/jemt.20084 Abstract: The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been intensely investigated due to the widespread abuse of this drug and its neurotoxic effects. In mice, MDMA neurotoxicity has been demonstrated for striatal dopamine (DA) terminals. However, the current literature has reported great variability in the effects induced by MDMA; this is partially due to changes in environmental conditions. For instance, elevated temperature and a crowded noisy environment markedly increase the neurotoxic effects induced by MDMA. The environmental factor loud noise is often present during ecstasy intake; however, only a few studies have analysed the consequence of a concomitant exposure to loud noise and ecstasy intake. In the present experimental work, we investigated whether nigrostriatal DA toxicity occurring after MDMA administration was potentiated in the presence of loud noise (100 dBA). We administered MDMA to C57/Black mice using a binging pattern for two durations of white noise exposure. We found a marked enhancement of MDMA toxicity (7.5 mg/Kg Ч4, 2 hours apart, i.p.) in the presence of white noise exposure lasting for at least 6 hours. The striatal damage was assessed by assaying DA levels as well as the loss of tyrosine hydroxylase (TH) and the increase in striatal glial fibrillary acidic protein (GFAP) immunohistochemistry. Since loud noise often accompanies ecstasy intake, the present findings call for more in-depth studies aimed at disclosing the fine mechanisms underlying this enhancement. Now why did I not think about investigating this  . Of course I would not have used white noise. I think it would be interesting to re-create this investigation using Trance, House, DnB, Dub, Trip-Hop, and some other types of music, perhaps soft rock, industrial, hip-hop etc. etc. The only problem I have with this investigation is that the mice do not actively seek out these types of music, or any music for that matter, nor do they forsee the involuntary use of MDMA whilst exposed to this music. Therfore I think the model is somewhat flawed as there are many factors that could cause potential problems in the basic design of the investigation. Not only are they stressing the mice with MDMA but they are subjecting them to abnormal amounts of noise. I am surprised the whole lot did not just up and die . Well I am being slightly facetious  .regards, m_e Unipolar Mania, It's good for life...
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methyl_ethyl (Guardian) 11-14-04 01:55 No 541464
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MDMA, Neuropsychobiology (Rated as: good read) |
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MDMA (3,4-Methylenedioxymethamphetamine) or Ecstasy: The Neuropsychobiological Implications of Taking It at Dances and Raves A.C. Parrott Neuropsychobiology 2004;50:329-335 DOI:10.1159/000080961 Abstract: MDMA (3,4-methylenedioxymethamphetamine) or 'ecstasy' is a ring-substituted amphetamine derivative, which is widely used as a recreational drug, most particularly at dances and raves. Around 80-95% of dancers/ravers report using ecstasy/MDMA, compared to 5-15% of young people in general. This paper will consider the possible contribution of stimulatory environmental conditions to the neuropsychobiological effects of MDMA. Animal research shows that heat and crowding potentiate the acute effects of MDMA. Social interaction and intravenous drug self-administration in laboratory rats are significantly enhanced when MDMA is given under hot ambient temperatures. Loud noise and physical activity can also contribute to the general overarousal. Furthermore, MDMA impairs homeostatic thermal control in rats, leading them to overheat in hot environments. The human implications of these findings are that the hot, noisy and overcrowded conditions at raves may be providing the ideal environment to heighten the acute drug response. In recreational users, the acute medical dangers of MDMA comprise a constellation of hyperthermia-related abreactions, which generally only occur when it has been taken in hot and crowded environments. MDMA is well established as a serotonergic neurotoxin in laboratory animals, but heat and overcrowding increase the degree of distal axon terminal loss. If this also occurs in humans, then the stimulatory environments of clubs and raves may heighten the likelihood of adverse neuropsychological sequelae in recreational ecstasy users. Consistent with this prediction, the extent of self-reported dancing/exercise when on MDMA has recently been shown to be associated with significantly more psychobiological problems afterwards. Unipolar Mania, It's good for life...
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