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

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Meyer, Jerrold S

2013-01-01

Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA). Most ecstasy users consume other substances as well, which complicates the interpretation of research in this field. The positively rated effects of MDMA consumption include euphoria, arousal, enhanced mood, increased sociability, and heightened perceptions; some common adverse reactions are nausea, headache, tachycardia, bruxism, and trismus. Lowering of mood is an aftereffect that is sometimes reported from 2 to 5 days after a session of ecstasy use. The acute effects of MDMA in ecstasy users have been attributed primarily to increased release and inhibited reuptake of serotonin (5-HT) and norepinephrine, along with possible release of the neuropeptide oxytocin. Repeated or high-dose MDMA/ecstasy use has been associated with tolerance, depressive symptomatology, and persisting cognitive deficits, particularly in memory tests. Animal studies have demonstrated that high doses of MDMA can lead to long-term decreases in forebrain 5-HT concentrations, tryptophan hydroxylase activity, serotonin transporter (SERT) expression, and visualization of axons immunoreactive for 5-HT or SERT. These neurotoxic effects may reflect either a drug-induced degeneration of serotonergic fibers or a long-lasting downregulation in 5-HT and SERT biosynthesis. Possible neurotoxicity in heavy ecstasy users has been revealed by neuroimaging studies showing reduced SERT binding and increased 5-HT2A receptor binding in several cortical and/or subcortical areas. MDMA overdose or use with certain other drugs can also cause severe morbidity and even death. Repeated use of MDMA may lead to dose escalation and the development of dependence, although such dependence is usually not as profound as is seen with many other drugs of abuse. MDMA/ecstasy-dependent patients are treated with standard addiction programs, since there are no specific programs for this substance and no proven

THC Prevents MDMA Neurotoxicity in Mice.

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Clara Touriño

2010-02-01

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

Ecstasy (MDMA) dependence.

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Jansen, K L

1999-01-07

Methylenedioxymethamphetamine (MDMA) is generally described as non-addictive. However, this report describes three cases in which criteria for dependence were met. A wider understanding that MDMA can be addictive in rare cases is important as very heavy use may cause lasting neuronal changes. This risk could be reduced with effective identification and treatment of dependent persons. In one case dependence was linked with self-medication of post-traumatic stress disorder (PTSD).

MDMA: interactions with other psychoactive drugs.

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Mohamed, Wael M Y; Ben Hamida, Sami; Cassel, Jean-Christophe; de Vasconcelos, Anne Pereira; Jones, Byron C

2011-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most widely abused illegal drugs. Some users self-report euphoria and an increased perception and feeling of closeness to others. When taken in warm environments, MDMA users may develop acute complications with potential fatal consequences. In rodents, MDMA increases locomotor activity and, depending on ambient temperature, may produce a dose-dependent, potentially lethal hyperthermia. Like most other recreational drugs, MDMA is frequently taken in combination with other substances including tobacco, EtOH, marijuana, amphetamines, cocaine and, caffeine. Although polydrug use is very common, the understanding of the effects of this multiple substance use, as well as the analysis of consequences of different drug-drug associations, received rather little attention. The purpose of this review is to summarize our current knowledge about the changes on MDMA-related behavior, pharmacology, and neurotoxicity associated with co-consumption of other drugs of abuse and psychoactive agents. Copyright © 2011 Elsevier B.V. All rights reserved.

Prosocial effects of MDMA: A measure of generosity.

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Kirkpatrick, Matthew; Delton, Andrew W; Robertson, Theresa E; de Wit, Harriet

2015-06-01

3,4-methylenedioxymethamphetamine (MDMA) produces "prosocial" effects that contribute to its recreational use. Few studies have examined the cognitive and behavioral mechanisms by which MDMA produces these effects. Here we examined the effect of MDMA on a specific prosocial effect, i.e. generosity, using a task in which participants make decisions about whether they or another person will receive money (Welfare Trade-Off Task; WTT). The project included one study without drug administration and one with MDMA. In Study 1, we administered the WTT to healthy adults (N = 361) and examined their performance in relation to measures of personality and socioeconomic status. In Study 2, healthy volunteers with MDMA experience (N = 32) completed the WTT after MDMA administration (0, 0.5, or 1.0 mg/kg). As expected, in both studies participants were more generous with a close friend than an acquaintance or stranger. In Study 1, WTT generosity was related to household income and trait Agreeableness. In Study 2, MDMA (1.0 mg/kg) increased generosity toward a friend but not a stranger, whereas MDMA (0.5 mg/kg) slightly increased generosity toward a stranger, especially among female participants. These data indicate that the WTT is a valuable, novel tool to assess a component of prosocial behavior, i.e. generosity to others. The findings support growing evidence that MDMA produces prosocial effects, but, as with oxytocin, these appear to depend on the social proximity of the relationships. The brain mechanisms underlying the construct of generosity, or the effects of MDMA on this measure, remain to be determined. © The Author(s) 2015.

Effects of stress and MDMA on hippocampal gene expression.

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Weber, Georg F; Johnson, Bethann N; Yamamoto, Bryan K; Gudelsky, Gary A

2014-01-01

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

Safety pharmacology of acute MDMA administration in healthy subjects.

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Vizeli, Patrick; Liechti, Matthias E

2017-05-01

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA-assisted psychotherapy. The present study characterized the safety pharmacology of single-dose administrations of MDMA (75 or 125 mg) using data from nine double-blind, placebo-controlled, crossover studies performed in the same laboratory in a total of 166 healthy subjects. The duration of the subjective effects was 4.2 ± 1.3 h (range: 1.4-8.2 h). The 125 mg dose of MDMA produced greater 'good drug effect' ratings than 75 mg. MDMA produced moderate and transient 'bad drug effect' ratings, which were greater in women than in men. MDMA increased systolic blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38°C in 33%, 29% and 19% of the subjects, respectively. These proportions of subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38°C were all significantly greater after 125 mg MDMA compared with the 75 mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of Complaints were dose-dependent and more frequent in females. MDMA did not affect liver or kidney function at EOS 29 ± 22 days after use. No serious adverse events occurred. In conclusion, MDMA produced predominantly acute positive subjective drug effects. Bad subjective drug effects and other adverse effects were significantly more common in women. MDMA administration was overall safe in physically and psychiatrically healthy subjects and in a medical setting. However, the risks of MDMA are likely higher in patients with cardiovascular disease and remain to be investigated in patients with psychiatric disorders.

The potential dangers of using MDMA for psychotherapy.

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Parrott, Andrew C

2014-01-01

MDMA has properties that may make it attractive for psychotherapy, although many of its effects are potentially problematic. These contrasting effects will be critically reviewed in order to assess whether MDMA could be safe for clinical usage. Early studies from the 1980s noted that MDMA was an entactogen, engendering feelings of love and warmth. However, negative experiences can also occur with MDMA since it is not selective in the thoughts or emotions it releases. This unpredictability in the psychological material released is similar to another serotonergic drug, LSD. Acute MDMA has powerful neurohormonal effects, increasing cortisol, oxytocin, testosterone, and other hormone levels. The release of oxytocin may facilitate psychotherapy, whereas cortisol may increase stress and be counterproductive. MDMA administration is followed by a period of neurochemical recovery, when low serotonin levels are often accompanied by lethargy and depression. Regular usage can also lead to serotonergic neurotoxicity, memory problems, and other psychobiological problems. Proponents of MDMA-assisted therapy state that it should only be used for reactive disorders (such as PTSD) since it can exacerbate distress in those with a prior psychiatric history. Overall, many issues need to be considered when debating the relative benefits and dangers of using MDMA for psychotherapy.

MDMA reinstates cocaine-seeking behaviour in mice.

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

2009-06-01

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

Effects of Stress and MDMA on Hippocampal Gene Expression

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Georg F. Weber

2014-01-01

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

Methylenedioxymethamphetamine (MDMA, 'Ecstasy': Neurodegeneration versus Neuromodulation

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Elena Puerta

2011-07-01

Full Text Available The amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’ is widely abused as a recreational drug due to its unique psychological effects. Of interest, MDMA causes long-lasting deficits in neurochemical and histological markers of the serotonergic neurons in the brain of different animal species. Such deficits include the decline in the activity of tryptophan hydroxylase in parallel with the loss of 5-HT and its main metabolite 5-hydoxyindoleacetic acid (5-HIAA along with a lower binding of specific ligands to the 5-HT transporters (SERT. Of concern, reduced 5-HIAA levels in the CSF and SERT density have also been reported in human ecstasy users, what has been interpreted to reflect the loss of serotonergic fibers and terminals. The neurotoxic potential of MDMA has been questioned in recent years based on studies that failed to show the loss of the SERT protein by western blot or the lack of reactive astrogliosis after MDMA exposure. In addition, MDMA produces a long-lasting down-regulation of SERT gene expression; which, on the whole, has been used to invoke neuromodulatory mechanisms as an explanation to MDMA-induced 5-HT deficits. While decreased protein levels do not necessarily reflect neurodegeneration, the opposite is also true, that is, neuroregulatory mechanisms do not preclude the existence of 5-HT terminal degeneration.

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

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

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Maternal MDMA administration in mice leads to neonatal growth delay.

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Kaizaki, Asuka; Tanaka, Sachiko; Yoshida, Takemi; Numazawa, Satoshi

2014-02-01

The psychoactive recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is widely abused. The fact that MDMA induces neurotoxic damage in serotonergic nerve endings is well known. However, the effects of MDMA on pregnant and neonatal animals remain unknown. Therefore, we studied the effects of gestational exposure to MDMA on birth, growth, and behavior of pups. Female BALB/c mice were orally administered either water (10 ml/kg) or MDMA (20 mg/10 ml/kg) from gestational day 1 to postnatal day (P) 21. MDMA did not affect the birth rate, but the survival rate of the pups significantly decreased. A significant reduction in body weight gain was observed in pups from MDMA-administered dams during P3-P21. Maternal MDMA treatment caused an attenuated cliff avoidance reaction and decreased motor function in the pups, as determined by the wire hanging test. These results suggest that MDMA treatment during pregnancy and lactation causes growth retardation and dysfunction of motor neurons in mouse pups.

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

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Harvey, Eric L; Baker, Lisa E

2016-02-01

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

Crime and Violence among MDMA Users in the United States

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Michael G. Vaughn

2015-03-01

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

NEURAL AND CARDIAC TOXICITIES ASSOCIATED WITH 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA)

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Baumann, Michael H.; Rothman, Richard B.

2009-01-01

(±)-3,4-Methylenedioxymethamphetamine (MDMA) is a commonly abused illicit drug which affects multiple organ systems. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been viewed as neurotoxicity. Recent data implicate MDMA in the development of valvular heart disease (VHD). The present paper reviews several issues related to MDMA-associated neural and cardiac toxicities. The hypothesis of MDMA neurotoxicit...

Sex differences in MDMA-induced toxicity in Sprague-Dawley rats

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Asl, Sara Soleimani; Mehdizadeh, Mehdi; Shahraki, Soudabeh Hamedi; Artimani, Tayebeh; Joghataei, Mohammad Taghi

2015-01-01

Summary Recent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to up-regulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones. PMID:26415786

Effects of MDMA on body temperature in humans

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Liechti, Matthias E

2014-01-01

Hyperthermia is a severe complication associated with the recreational use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). In this review, the clinical laboratory studies that tested the effects of MDMA on body temperature are summarized. The mechanisms that underlie the hyperthermic effects of MDMA in humans and treatment of severe hyperthermia are presented. The data show that MDMA produces an acute and dose-dependent rise in core body temperature in healthy subjects. The increase in body temperature is in the range of 0.2-0.8°C and does not result in hyperpyrexia (>40°C) in a controlled laboratory setting. However, moderately hyperthermic body temperatures >38.0°C occur frequently at higher doses, even in the absence of physical activity and at room temperature. MDMA primarily releases serotonin and norepinephrine. Mechanistic clinical studies indicate that the MDMA-induced elevations in body temperature in humans partially depend on the MDMA-induced release of norepinephrine and involve enhanced metabolic heat generation and cutaneous vasoconstriction, resulting in impaired heat dissipation. The mediating role of serotonin is unclear. The management of sympathomimetic toxicity and associated hyperthermia mainly includes sedation with benzodiazepines and intravenous fluid replacement. Severe hyperthermia should primarily be treated with additional cooling and mechanical ventilation. PMID:27626046

Oxytocin receptor gene variation predicts subjective responses to MDMA.

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Bershad, Anya K; Weafer, Jessica J; Kirkpatrick, Matthew G; Wardle, Margaret C; Miller, Melissa A; de Wit, Harriet

2016-12-01

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here, we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this three-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg, and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.

MDMA and the "ecstasy paradigm".

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Cole, Jon C

2014-01-01

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

Serotonin antagonists fail to alter MDMA self-administration in rats.

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Schenk, Susan; Foote, Jason; Aronsen, Dane; Bukholt, Natasha; Highgate, Quenten; Van de Wetering, Ross; Webster, Jeremy

2016-09-01

Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use. Copyright © 2016 Elsevier Inc. All rights reserved.

Potential Psychiatric Uses for MDMA

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Yazar?Klosinski, BB; Mithoefer, MC

2017-01-01

Phase II trials of 3,4?methylenedioxymethamphetamine (MDMA)?assisted psychotherapy have demonstrated initial safety and efficacy for treatment of posttraumatic stress disorder (PTSD), with potential for expansion to depression and anxiety disorders. In these trials, single doses of MDMA are administered in a model of medication?assisted psychotherapy, differing from trials involving daily drug administration without psychotherapy. This model presents an opportunity to utilize accelerated regu...

Neuroimaging in human MDMA (Ecstasy) users: A cortical model

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Cowan, Ronald L; Roberts, Deanne M; Joers, James M

2009-01-01

MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. MDMA and Ecstasy are often used synonymously but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and non-human primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long-lasting reductions in markers of brain serotonin (5-HT) that appear specific to fine diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long-lasting or permanent 5-HT axon damage or loss, and the widespread role of 5-HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long-lasting changes in brain function consistent with 5-HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research. PMID:18991874

Tolerance to the locomotor-activating effects of 3,4-methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking in rats

OpenAIRE

Ball, Kevin T.; Slane, Mylissa

2014-01-01

Pre-clinical studies of individual differences in addiction vulnerability have been increasing over recent years, but the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little attention in this regard. Previously, we reported large individual differences both in rats' initial behavioral response to experimenter-administered MDMA and their degree of behavioral sensitization to repeated administration. To determine whether these differences coul...

Discrete memory impairments in largely pure chronic users of MDMA.

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Wunderli, Michael D; Vonmoos, Matthias; Fürst, Marina; Schädelin, Katrin; Kraemer, Thomas; Baumgartner, Markus R; Seifritz, Erich; Quednow, Boris B

2017-10-01

Chronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulant-naïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (d primary =.90, d polydrug =1.21), followed by working memory (d primary =.52, d polydrug =.96), executive functions (d primary =.46, d polydrug =.86), and attention (d primary =.23, d polydrug =.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans

Science.gov (United States)

Hysek, CM; Schmid, Y; Rickli, A; Simmler, LD; Donzelli, M; Grouzmann, E; Liechti, ME

2012-01-01

BACKGROUND AND PURPOSE The use of ±3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is associated with cardiovascular complications and hyperthermia. EXPERIMENTAL APPROACH We assessed the effects of the α1- and β-adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, four-period crossover design. KEY RESULTS Carvedilol reduced MDMA-induced elevations in blood pressure, heart rate and body temperature. Carvedilol did not affect the subjective effects of MDMA including MDMA-induced good drug effects, drug high, drug liking, stimulation or adverse effects. Carvedilol did not alter the plasma exposure to MDMA. CONCLUSIONS AND IMPLICATIONS α1- and β-Adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychotropic effects. Carvedilol could be useful in the treatment of cardiovascular and hyperthermic complications associated with ecstasy use. PMID:22404145

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

Science.gov (United States)

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

2014-09-01

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

Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

Science.gov (United States)

Hysek, Cédric M; Simmler, Linda D; Schillinger, Nathalie; Meyer, Nicole; Schmid, Yasmin; Donzelli, Massimiliano; Grouzmann, Eric; Liechti, Matthias E

2014-03-01

Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).

Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.

Science.gov (United States)

Aguilar, M A; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J

2015-04-01

Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence. Copyright © 2015 Elsevier Inc. All rights reserved.

Stereoselective effects of MDMA on inhibition of monoamine uptake

International Nuclear Information System (INIS)

Steele, T.D.; Nichols, D.E.; Yim, G.K.W.

1986-01-01

The R(-)-isomers of hallucinogenic phenylisopropylamines are most active, whereas the S(+)-enantiomers of amphetamine (AMPH) and methylenedioxymethamphetamine (MDMA) are more potent centrally. To determine if MDMA exhibits stereoselective effects at the biochemical level that resemble either those of amphetamine or the potent hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM), the ability of the isomers of MDMA, AMPH and DOM to inhibit uptake of radiolabelled monoamines into synaptosomes was measured. AMPH was more potent than MDMA in inhibiting uptake of 3 H-norepinephrine (NE) into hypothalamic synaptosomes and 3 H-dopamine (DA) into striatal synaptosomes. The S(+)-isomer was more active in each case. MDMA was more potent than AMPH in inhibiting uptake of 3 H-serotonin (5-HT) into hippocampal synaptosomes and exhibited a high degree of stereoselectivity, in favor of the S(+)-isomer. DOM showed only minimal activity in inhibiting uptake of any monoamine (IC 50 > 10 -5 M). These results suggest that MDMA exhibits stereoselective effects similar to those of amphetamine on monoamine uptake inhibition, a parameter that is unrelated to the mechanism of action of the hallucinogen DOM

Human Pharmacology of Mephedrone in Comparison with MDMA.

Science.gov (United States)

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

2016-10-01

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

MDMA alters emotional processing and facilitates positive social interaction.

Science.gov (United States)

Wardle, Margaret C; de Wit, Harriet

2014-10-01

±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") produces "prosocial" effects, such as feelings of empathy and closeness, thought to be important to its abuse and its value in psychotherapy. However, it is not fully understood how MDMA alters basic emotional processes to produce these effects, or whether it produces corresponding changes in actual social behavior. Here, we examined how MDMA affects perceptions of and responses to emotional expressions, and tested its effects on behavior during a social interaction. We also examined whether MDMA's prosocial effects related to a measure of abuse liability. Over three sessions, 36 healthy volunteers with previous ecstasy use received MDMA (0.75, 1.5 mg/kg) and placebo under double-blind conditions. We measured (i) mood and cardiovascular effects, (ii) perception of and psychophysiological responses to emotional expressions, (iii) use of positive and negative words in a social interaction, and (iv) perceptions of an interaction partner. We then tested whether these effects predicted desire to take the drug again. MDMA slowed perception of angry expressions, increased psychophysiological responses to happy expressions, and increased positive word use and perceptions of partner empathy and regard in a social interaction. These effects were not strongly related to desire to take the drug again. MDMA alters basic emotional processes by slowing identification of negative emotions and increasing responses to positive emotions in others. Further, it positively affects behavior and perceptions during actual social interaction. These effects may contribute to the efficacy of MDMA in psychotherapy, but appear less closely related to its abuse potential.

A mechanistic insight into MDMA-mediated hepatotoxicity

NARCIS (Netherlands)

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

2011-01-01

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

Investigating the potential neurotoxicity of Ecstasy (MDMA): an imaging approach

NARCIS (Netherlands)

Reneman, Liesbeth; Booij, Jan; Majoie, Charles B. L. M.; van den Brink, Wim; den Heeten, Gerard J.

2001-01-01

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

Differential effects of MDMA and methylphenidate on social cognition.

Science.gov (United States)

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

2014-09-01

Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective 'empathogenic' effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug. © The Author(s) 2014.

Progress and promise for the MDMA drug development program.

Science.gov (United States)

Feduccia, Allison A; Holland, Julie; Mithoefer, Michael C

2018-02-01

Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug "Ecstasy." MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.

Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin.

Science.gov (United States)

Benzenhöfer, Udo; Passie, Torsten

2010-08-01

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. We analysed systematically Shulgin's original publications on MDMA, his publications on the history of MDMA and his laboratory notebook. 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. 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.

Occipital cortical proton MRS at 4 Tesla in human moderate MDMA polydrug users.

Science.gov (United States)

Cowan, Ronald L; Bolo, Nicolas R; Dietrich, Mary; Haga, Erica; Lukas, Scott E; Renshaw, Perry F

2007-08-15

The recreational drug MDMA (3,4, methylenedioxymethamphetamine; sold under the street name of Ecstasy) is toxic to serotonergic axons in some animal models of MDMA administration. In humans, MDMA use is associated with alterations in markers of brain function that are pronounced in occipital cortex. Among neuroimaging methods, magnetic resonance spectroscopy (MRS) studies of brain metabolites N-acetylaspartate (NAA) and myoinositol (MI) at a field strength of 1.5 Tesla (T) reveal inconsistent results in MDMA users. Because higher field strength proton MRS has theoretical advantages over lower field strengths, we used proton MRS at 4.0 T to study absolute concentrations of occipital cortical NAA and MI in a cohort of moderate MDMA users (n=9) versus non-MDMA using (n=7) controls. Mean NAA in non-MDMA users was 10.47 mM (+/-2.51), versus 9.83 mM (+/-1.94) in MDMA users. Mean MI in non-MDMA users was 7.43 mM (+/-.68), versus 6.57 mM (+/-1.59) in MDMA users. There were no statistical differences in absolute metabolite levels for NAA and MI in occipital cortex of MDMA users and controls. These findings are not supportive of MDMA-induced alterations in NAA or MI levels in this small sample of moderate MDMA users. Limitations to this study suggest caution in the interpretation of these results.

Proton magnetic resonance spectroscopy in ecstasy (MDMA) users.

Science.gov (United States)

Daumann, Jörg; Fischermann, Thomas; Pilatus, Ulrich; Thron, Armin; Moeller-Hartmann, Walter; Gouzoulis-Mayfrank, Euphrosyne

2004-05-20

The popular recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has well-recognized neurotoxic effects upon central serotonergic systems in animal studies. In humans, the use of MDMA has been linked to cognitive problems, particularly to deficits in long-term memory and learning. Recent studies with proton magnetic resonance spectroscopy (1H MRS) have reported relatively low levels of the neuronal marker N-acetylaspartate (NAA) in MDMA users, however, these results have been ambiguous. Moreover, the only available 1H MRS study of the hippocampus reported normal findings in a small sample of five MDMA users. In the present study, we compared 13 polyvalent ecstasy users with 13 matched controls. We found no differences between the NAA/creatine/phosphocreatine (Cr) ratios of users and controls in neocortical regions, and only a tendency towards lower NAA/Cr ratios in the left hippocampus of MDMA users. Thus, compared with cognitive deficits, 1H MRS appears to be a less sensitive marker of potential neurotoxic damage in ecstasy users. Copyright 2004 Elsevier Ireland Ltd.

Designer Drug Confusion: A Focus on MDMA.

Science.gov (United States)

Beck, Jerome; Morgan, Patricia A.

1986-01-01

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

From ecstasy to MDMA: Recreational drug use, symbolic boundaries, and drug trends.

Science.gov (United States)

Edland-Gryt, Marit; Sandberg, Sveinung; Pedersen, Willy

2017-12-01

Ecstasy pills with MDMA as the main ingredient were introduced in many European countries in the 1980s, and were often linked to the rave and club scenes. However, use gradually levelled off, in part as a response to increased concerns about possible mental health consequences and fatalities. Extensive use of MDMA now seems to be re-emerging in many countries. In this study, we investigated the cultural and social meaning associated with MDMA use in Oslo, Norway, with an emphasis on how users distinguish MDMA crystals and powder from "old ecstasy pills". Qualitative in-depth interviews (n=31, 61,3% males) were conducted with young adult party-goers and recreational MDMA/ecstasy users (20-34 years old, mean age 26.2 years). Research participants emphasised three important perceived differences between the MDMA crystals and ecstasy pills: (i) The effects of MDMA were described as better than ecstasy; (ii) MDMA was regarded as a safer drug; (iii) Users of MDMA crystals were described as more distinct from and less anchored in out-of-fashion rave culture than those using ecstasy. These differences were an important part of the symbolic boundary work MDMA users engaged in when justifying their drug use. MDMA has re-emerged as an important psychoactive substance in Oslo's club scene. One important reason for this re-emergence seems to be its perceived differentiation from ecstasy pills, even though the active ingredient in both drugs is MDMA. This perceived distinction between MDMA and ecstasy reveals the importance of social and symbolic meanings in relation to psychoactive substance use. Insights from this study can be important in terms of understanding how trends in drug use develop and how certain drugs gain or lose popularity. Copyright © 2017 Elsevier B.V. All rights reserved.

3,4-methylenedioxymethamphetamine (MDMA): current perspectives

OpenAIRE

Meyer, Jerry

2013-01-01

Jerrold S Meyer Department of Psychology, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA, USA Abstract: Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA). Most ecstasy users consume other substances as well, which complicates the interpretation of research in this field. The positively rated effects of MDMA consumption include euphoria, arousal, enhanced mood, increased sociability, and heighten...

A Cross-Reactivity of Fenofibric Acid With MDMA DRI Assay.

Science.gov (United States)

Bugier, Sarah; Garcia-Hejl, Carine; Vest, Philippe; Plantamura, Julie; Chianea, Denis; Renard, Christophe

2016-09-01

Within the framework of routine fitness examinations, French Air Force military crew underwent urine testing for 3,4 methylenedioxymetamphetamine (MDMA [ecstasy]). The cross-reactivity of a dyslipidemic drug, fenofibrate, with an MDMA immunoassay was studied and confirmed on a large population sample. A 3-year retrospective study was performed on the MDMA DRI Ecstasy Assay on the Unicel DXC 600. In the event of positive test result, a confirmatory testing was carried out by gas chromatography/mass spectrometry (GC/MS) to establish the presence of MDMA. When analysis by GC/MS did not confirm the presence of MDMA, a false-positive result was suspected and the samples were analyzed by high-performance liquid chromatography-mass spectrometry to identify a potential interfering substance. A total of 15,169 urine samples, from 7,803 patients, were tested for 3 years. Of the tested samples, 22 (0.15%) were positive by DRI Ecstasy Assay. None of them were positive by GC/MS. A cross-reactivity of fenofibrate's metabolite with MDMA using this assay was systematically found. Fenofibrate's interference with MDMA immunoassay was confirmed. Fenofibrate being widely prescribed, physicians had to be alerted that this treatment could lead to false-positive results. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

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

Science.gov (United States)

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

2014-12-01

Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning Task. Profile of Mood State and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigour, arousal, elation) and negative mood effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of salicylate on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats.

Science.gov (United States)

Yeh, S Y

1997-11-01

The drug 3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that causes hyperthermia and depletion of serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation of neurotoxic metabolites of MDMA, e.g., 2,4,5-trihydroxy-methamphetamine and 2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals. The present study was designed to determine whether the hydroxyl free-radical-trapping agent salicylate could provide protection against MDMA neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg, calculated as free acid) was injected interperitoneally (i.p.) 1 h before subcutaneous (s.c.) injections of MDMA (20 mg/kg as base). In the chronic studies, sodium salicylate (3.1-100 mg/kg) was injected i.p. 1 h before repeated s.c. injections of MDMA (10 mg/kg as base, twice daily, at 0830 and 1730 h for 4 consecutive days). Repeated MDMA administration depleted contents of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum. Coadministration of salicylate plus MDMA did not significantly alter MDMA-induced depletion of 5-HT and 5-HIAA in these tissues. Thus, salicylate, a hydroxyl free-radical-trapping agent, does not protect against MDMA-induced hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that MDMA-induced neurotoxicity may occur mainly through the production of superoxide or other radicals rather than hydroxyl free radicals. Salicylate actually potentiated MDMA-induced hyperthermia and lethality, findings that might be of clinical relevance.

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

Science.gov (United States)

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

2015-03-01

This work examines the organic impurity profile of 3,4-methylenedioxymethamphetamine (MDMA) that has been synthesised from catechol (1,2-dihydroxybenzene), a common chemical reagent available in industrial quantities. The synthesis of MDMA from catechol proceeded via the common MDMA precursor safrole. Methylenation of catechol yielded 1,3-benzodioxole, which was brominated and then reacted with magnesium allyl bromide to form safrole. Eight organic impurities were identified in the synthetic safrole. Safrole was then converted to 3,4-methylenedioxyphenyl-2-propanone (MDP2P) using two synthetic methods: Wacker oxidation (Route 1) and an isomerisation/peracid oxidation/acid dehydration method (Route 2). MDMA was then synthesised by reductive amination of MDP2P. Thirteen organic impurities were identified in MDMA synthesised via Route 1 and eleven organic impurities were identified in MDMA synthesised via Route 2. Overall, organic impurities in MDMA prepared from catechol indicated that synthetic safrole was used in the synthesis. The impurities also indicated which of the two synthetic routes was utilised. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Social Cognition and Interaction in Chronic Users of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy").

Science.gov (United States)

Wunderli, Michael D; Vonmoos, Matthias; Treichler, Lorena; Zeller, Carmen; Dziobek, Isabel; Kraemer, Thomas; Baumgartner, Markus R; Seifritz, Erich; Quednow, Boris B

2018-04-01

The empathogen 3,4-methylenedioxymethamphetamine (MDMA) is the prototypical prosocial club drug inducing emotional openness to others. It has recently been shown that acutely applied 3,4-MDMA in fact enhances emotional empathy and prosocial behavior, while it simultaneously decreases cognitive empathy. However, the long-term effects of 3,4-MDMA use on socio-cognitive functions and social interactions have not been investigated yet. Therefore, we examined emotional and cognitive empathy, social decision-making, and oxytocin plasma levels in chronic 3,4-MDMA users. We tested 38 regular but recently abstinent 3,4-MDMA users and 56 3,4-MDMA-naïve controls with the Movie for the Assessment of Social Cognition, the Multifaceted Empathy Test, and the Distribution Game and the Dictator Game. Drug use was objectively quantified by 6-month hair analyses. Furthermore, oxytocin plasma levels were determined in smaller subgroups (24 3,4-MDMA users, 9 controls). 3,4-MDMA users showed superior cognitive empathy compared with controls in the Multifaceted Empathy Test (Cohen's d=.39) and in the Movie for the Assessment of Social Cognition (d=.50), but they did not differ from controls in emotional empathy. Moreover, 3,4-MDMA users acted less self-serving in the Distribution Game. However, within 3,4-MDMA users, multiple regression analyses showed that higher 3,4-MDMA concentrations in hair were associated with lower cognitive empathy (βMDMA=-.34, t=-2.12, P<.05). Oxytocin plasma concentrations did not significantly differ between both groups. We conclude that people with high cognitive empathy abilities and pronounced social motivations might be more prone to 3,4-MDMA consumption. In contrast, long-term 3,4-MDMA use might nevertheless have a detrimental effect on cognitive empathy capacity.

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

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

2014-03-01

Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; pEcstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed. © 2013 Published by Elsevier B.V. and ECNP.

Effects of Stress and MDMA on Hippocampal Gene Expression

OpenAIRE

Weber, Georg F.; Johnson, Bethann N.; Yamamoto, Bryan K.; Gudelsky, Gary A.

2014-01-01

MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neuro...

3,4-Methylenedioxymethamphetamine's (MDMA's) Impact on Posttraumatic Stress Disorder.

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White, C Michael

2014-07-01

Review the current literature assessing the role of 3,4-methylenedioxymethamphetamine (MDMA) on posttraumatic stress disorder (PTSD). OVID MEDLINE search (1960-February 2014) using the terms MDMA, 3,4-methylenedioxymethamphetamine, Molly, and Ecstasy crossed with posttraumatic stress disorder with backwards citation tracking using references from procured articles. English language studies assessing MDMA in patients with PTSD. Three randomized controlled trials (RCTs) were conducted along with follow-up open-label and extension evaluations. In the 3 RCTs, therapy with MDMA-assisted psychotherapy is promising, with reductions in PTSD rating scale scores (Clinician-Administered PTSD Scale, Severity of Symptoms Scale for PTSD Scale), although 2 of 3 trials did not show significant results, and all three had methodological limitations. The direction of effect for all trials was toward benefit in patients who were refractory to other PTSD therapies; the percentage reductions on rating scores ranged from 23% to 68%; and in 1 trial, the effect was sustained over a long period of time. MDMA ingestion without sustained psychotherapy over a 6- to 8-hour period is unlikely to be beneficial; trying to prolong the duration of effect with supplemental dosing is unlikely to provide additional benefits; and there are adverse effects on blood pressure and heart rate that should be appreciated. These studies used unadulterated MDMA with known and reproducible potency, which may not happen with street purchase of the product. MDMA-assisted psychotherapy may be an effective therapy in refractory PTSD but needs further evaluation to determine its place in contemporary therapy. © The Author(s) 2014.

Intimate insight: MDMA changes how people talk about significant others

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

2015-01-01

Rationale ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions. Method 35 healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a 5-min standardized talking task during which they discussed a close personal relationship (e.g., a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g., words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker’s Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers. Results Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions. Conclusions These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction. PMID:25922420

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

NARCIS (Netherlands)

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

2009-01-01

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

Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction.

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Quednow, Boris B; Jessen, Frank; Kuhn, Kai-Uwe; Maier, Wolfgang; Daum, Irene; Wagner, Michael

2006-05-01

Chronic administration of the common club drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is associated with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains of rodents and non-human primates, and evidence suggests that recreational MDMA consumption may also affect the human serotonergic system. Moreover, it was consistently shown that abstinent MDMA users have memory deficits. Recently, it was supposed that these deficits are an expression of a temporal or rather hippocampal dysfunction caused by the serotonergic neurotoxicity of MDMA. The aim of this study is to examine the memory deficits of MDMA users neuropsychologically in order to evaluate the role of different brain regions. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users and 19 male drug-naive control subjects were examined with a German version of the Rey Auditory Verbal Learning Test (RAVLT). MDMA users showed widespread and marked verbal memory deficits, compared to drug-naive controls as well as compared to cannabis users, whereas cannabis users did not differ from control subjects in their memory performance. MDMA users revealed impairments in learning, consolidation, recall and recognition. In addition, they also showed a worse recall consistency and strong retroactive interference whereby both measures were previously associated with frontal lobe function. There was a significant correlation between memory performance and the amount of MDMA taken. These results suggest that the memory deficits of MDMA users are not only the result of a temporal or hippocampal dysfunction, but also of a dysfunction of regions within the frontal cortex.

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

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

2009-11-01

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

Oxytocin and MDMA ('Ecstasy') enhance social reward in rats.

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Ramos, Linnet; Hicks, Callum; Caminer, Alex; Goodwin, Jack; McGregor, Iain S

2015-07-01

Oxytocin (OT), vasopressin (AVP) and 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') all increase social interaction in rats, perhaps by enhancing the rewarding value of social encounters. Here, we used the conditioned place preference (CPP) paradigm to assess the intrinsic rewarding effects of OT, AVP and MDMA, and whether these effects are enhanced by the presence of a conspecific, or a dynamic, tactile object (a tennis ball). Adult male rats received conditioning sessions in a CPP apparatus twice a day (vehicle at 10 a.m., drug at 3 p.m.). Experiment 1 involved conditioning with OT (0.5 mg/kg, intraperitoneal (i.p.)), AVP (0.005 mg/kg, i.p.) or MDMA (5 mg/kg, i.p.). Experiments 2 and 3 involved conditioning with the same treatments but in the presence of a conspecific receiving the same treatment (social-CPP) or in the presence of a tennis ball (object-CPP), respectively. Conditioned place preference was assessed 24 h, 2 weeks and 4 weeks later. OT, AVP and MDMA did not produce a conventional CPP. However, when the conditioning environment also contained a conspecific both OT and MDMA induced a significant CPP lasting for at least 4 weeks. Rats given OT and MDMA also developed a more modest yet significant CPP for the environment where they encountered a tennis ball. These results indicate that OT and MDMA can augment the rewarding effects of social interaction, but also interaction with a dynamic and tactile non-social object. AVP does not condition social- or object-CPPs and may promote social proximity by inducing generalized anxiety and defensive aggregation.

Monitoring MDMA metabolites in urban wastewater as novel biomarkers of consumption.

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González-Mariño, Iria; Zuccato, Ettore; Santos, Miquel M; Castiglioni, Sara

2017-05-15

Consumption of 3,4-methylendioxymethamphetamine (MDMA) has been always estimated by measuring the parent substance through chemical analysis of wastewater. However, this may result in an overestimation of the use if the substance is directly disposed in sinks or toilets. Using specific urinary metabolites may overcome this limitation. This study investigated for the first time the suitability of a panel of MDMA metabolites as biomarkers of consumption, considering the specific criteria recently proposed, i.e. being detectable and stable in wastewater, being excreted in a known percentage in urine, and having human excretion as the sole source. A new analytical method was developed and validated for the extraction and analysis of MDMA and three of its main metabolites in wastewater. 24-h composite raw wastewater samples from three European cities were analysed and MDMA use was back-calculated. Results from single MDMA loads, 4-hydroxy-3-methoxymethamphetamine (HMMA) loads and from the sum of MDMA, HMMA and 4-hydroxy-3-methoxyamphetamine (HMA) loads were in line with the well-known recreational use of this drug: consumption was higher during the weekend in all cities. HMMA and HMA turned out to be suitable biomarkers of consumption; however, concentrations measured in wastewater did not resemble the expected pharmacokinetic profiles, quite likely due to the very limited information available on excretion profiles. Different options were tested to back-calculate MDMA use, including the sum of MDMA and its metabolites, to balance the biases associated with each single substance. Nevertheless, additional pharmacokinetic studies are urgently needed in order to get more accurate excretion rates and, therefore, improve the estimates of MDMA use. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

2014-05-01

The substituted β-keto amphetamine mephedrone (4-methylmethcathinone) was banned in the UK in April 2010 but continues to be used recreationally in the UK and elsewhere. Users have compared its psychoactive effects to those of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). This review critically examines the preclinical data on mephedrone that have appeared over the last 2-3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However, both of these responses are of short duration following mephedrone compared with MDMA probably because mephedrone has a short plasma half-life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces a neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. Mephedrone and MDMA both induce release of dopamine and 5-HT in the brain as shown by in vivo and in vitro studies. The effect on 5-HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for the dopamine and 5-HT transporters in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self-administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects, but also differs from other cathinones. © 2014 The British Pharmacological Society.

The History of MDMA as an Underground Drug in the United States, 1960-1979.

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Passie, Torsten; Benzenhöfer, Udo

2016-01-01

MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. "ecstasy") was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA "on the street" was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of "legal alternatives" for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first "hot region" of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major "hot region" of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.

Can MDMA play a role in the treatment of substance abuse?

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Jerome, Lisa; Schuster, Shira; Yazar-Klosinski, B Berra

2013-03-01

A wider array of treatments are needed for people with substance abuse disorders. Some psychedelic compounds have been assessed as potential substance abuse treatments with promising results. MDMA may also help treat substance abuse based on shared features with psychedelic compounds and recent reports indicating that MDMAassisted psychotherapy can reduce symptoms of PTSD. Narrative reports and data from early investigations found that some people reduced or eliminated their substance use after receiving MDMA, especially in a therapeutic setting. MDMA is a potent monoamine releaser with sympathomimetic effects that may indirectly activate 5-HT2A receptors. It increases interpersonal closeness and prosocial feelings, potentially through oxytocin release. Findings suggest that ecstasy, material represented as containing MDMA, is associated with deleterious long-term effects after heavy lifetime use, including fewer serotonin transporter sites and impaired verbal memory. Animal and human studies demonstrate moderate abuse liability for MDMA, and this effect may be of most concern to those treating substance abuse disorders. However, subjects who received MDMA-assisted psychotherapy in two recent clinical studies were not motivated to seek out ecstasy, and tested negative in random drug tests during follow-up in one study. MDMA could either directly treat neuropharmacological abnormalities associated with addiction, or it could indirectly assist with the therapeutic process or reduce symptoms of comorbid psychiatric conditions, providing a greater opportunity to address problematic substance use. Studies directly testing MDMA-assisted psychotherapy in people with active substance abuse disorder may be warranted.

The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure.

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Rodríguez-Arias, Marta; Vaccaro, Sonia; Arenas, M Carmen; Aguilar, María A; Miñarro, José

2015-03-15

Exposure to drugs such as ethanol or cocaine during adolescence induces alterations in the central nervous system that are modulated by the novelty-seeking trait. Our aim was to evaluate the influence of this trait on the long-term effects of MDMA administration during adolescence on spontaneous behavior and conditioned rewarding effects in adulthood. Adolescent mice were classified as high or low novelty seekers (HNS or LNS) according to the hole-board test and received either MDMA (0, 10 or 20mg/kg PND 33-42) or saline. Three weeks later, having entered adulthood (PND>68), one set of mice performed the elevated plus maze and social interaction tests, while another set performed the conditioning place preference (CPP) test induced by cocaine-(1mg/kg) or MDMA-(1mg/kg). Only HNS mice treated with MDMA during adolescence acquired CPP in adulthood with a non-effective dose of cocaine or MDMA. Although it did not produce changes in motor activity, exposure to MDMA during adolescence was associated with more aggressive behaviors (threat and attack) and increased social contacts in HNS mice, while an anxiolytic effect was noted in LNS mice pre-treated with the highest dose of MDMA (20mg/kg). Administration of MDMA (10 or 20mg/kg) induced a decrease in DA levels in the striatum in LNS mice only and lower striatal serotonin levels in mice treated with the highest MDMA dose. Our findings show that adolescent MDMA exposure results in higher sensitivity to the conditioned reinforcing properties of MDMA and cocaine in adult HNS mice, which suggests that the relationship between exposure to MDMA in adolescence and a higher probability of substance is a feature of high novelty seekers only. Copyright © 2015. Published by Elsevier Inc.

Memory performance in abstinent 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") users.

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Groth-Marnat, Gary; Howchar, Hennedy; Marsh, Ali

2007-02-01

Research with animals and humans has suggested that acute and subacute use of 3,4-methylenedioxymethamphetamine (MDMA "ecstasy") may lead to memory impairment. However, research is limited by (1) low power due to small sample sizes, (2) the possible confound of polydrug use, and (3) the failure to consider intelligence as a covariate. The present study compared the memory performance on the Wechsler Memory Scale-III of 26 abstinent (2-wk. minimum) recreational MDMA users with 26 abstinent (2-wk. minimum) recreational polydrug users. Despite significantly greater polydrug use amongst these MDMA users, no significant group differences in memory were observed. Regression of total lifetime amount of MDMA use also did not predict memory performance after accounting for intelligence. In addition, the length of time since abstinence (at least 2 wk.) was not associated with an increase in memory performance. Greater total lifetime cocaine use, rather than total lifetime MDMA use, was significantly associated with greater decrements in General Memory and Delayed Verbal Memory performance.

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

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

2013-06-01

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

Nonlinear pharmacokinetics of (+/-)3,4-methylenedioxymethamphetamine (MDMA) and its pharmacodynamic consequences in the rat.

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Concheiro, Marta; Baumann, Michael H; Scheidweiler, Karl B; Rothman, Richard B; Marrone, Gina F; Huestis, Marilyn A

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA's safety are needed. We evaluated MDMA's pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (±)-3,4-dihydroxymethamphetamine (HHMA), (±)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (±)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography-tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 ± 47.1 ng/ml, HHMA and HMMA were major metabolites, and MDMA was metabolized to MDA. After 5- and 10-mg/kg doses, MDMA areas under the curve (AUCs) were 3- and 10-fold greater than those after 2.5 mg/kg; HHMA and HMMA AUC values were relatively constant across doses; and MDA AUC values were greater than dose-proportional. Our data provide decisive in vivo evidence that MDMA and MDA display nonlinear accumulation via metabolic autoinhibition in the rat. Importantly, 5-HT syndrome severity correlated with MDMA concentrations (r = 0.8083; P MDMA's behavioral and hyperthermic effects may involve distinct mechanisms. Given key similarities between MDMA pharmacokinetics in rats and humans, data from rats can be useful when provided at clinically relevant doses.

Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

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Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

2017-01-01

3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

Potential Psychiatric Uses for MDMA.

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Yazar-Klosinski, B B; Mithoefer, M C

2017-02-01

Phase II trials of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have demonstrated initial safety and efficacy for treatment of posttraumatic stress disorder (PTSD), with potential for expansion to depression and anxiety disorders. In these trials, single doses of MDMA are administered in a model of medication-assisted psychotherapy, differing from trials involving daily drug administration without psychotherapy. This model presents an opportunity to utilize accelerated regulatory pathways, such as the US Food and Drug Administration (FDA) Breakthrough Therapy Designation, to most effectively and expeditiously test such novel approaches. © 2016, The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects

NARCIS (Netherlands)

Reneman, Liesbeth; de Win, Maartje M. L.; van den Brink, Wim; Booij, Jan; den Heeten, Gerard J.

2006-01-01

Users of ecstasy (3,4-methylenedioxymethamphetamine; MDMA) may be at risk of developing MDMA-induced injury to the serotonin (5-HT) system. Previously, there were no methods available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in

Effects of MDMA on olfactory memory and reversal learning in rats.

Science.gov (United States)

Hawkey, Andrew; April, L Brooke; Galizio, Mark

2014-10-01

The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0 mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0 mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Elisabet Cuyàs

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

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.

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Taghizadeh, Ghorban; Pourahmad, Jalal; Mehdizadeh, Hajar; Foroumadi, Alireza; Torkaman-Boutorabi, Anahita; Hassani, Shokoufeh; Naserzadeh, Parvaneh; Shariatmadari, Reyhaneh; Gholami, Mahdi; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2016-10-01

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function. Copyright © 2016 Elsevier Inc. All rights reserved.

MDMA-induced neurotoxicity of serotonin neurons involves autophagy and rilmenidine is protective against its pathobiology.

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Mercer, Linda D; Higgins, Gavin C; Lau, Chew L; Lawrence, Andrew J; Beart, Philip M

2017-05-01

Toxicity of 3,4-methylenedioxymethamphetamine (MDMA) towards biogenic amine neurons is well documented and in primate brain predominantly affects serotonin (5-HT) neurons. MDMA induces damage of 5-HT axons and nerve fibres and intracytoplasmic inclusions. Whilst its pathobiology involves mitochondrially-mediated oxidative stress, we hypothesised MDMA possessed the capacity to activate autophagy, a proteostatic mechanism for degradation of cellular debris. We established a culture of ventral pons from embryonic murine brain enriched in 5-HT neurons to explore mechanisms of MDMA neurotoxicity and recruitment of autophagy, and evaluated possible neuroprotective actions of the clinically approved agent rilmenidine. MDMA (100 μM-1 mM) reduced cell viability, like rapamycin (RM) and hydrogen peroxide (H 2 O 2 ), in a concentration- and time-dependent manner. Immunocytochemistry revealed dieback of 5-HT arbour: MDMA-induced injury was slower than for RM and H 2 O 2 , neuritic blebbing occurred at 48 and 72 h and Hoechst labelling revealed nuclear fragmentation with 100 μM MDMA. MDMA effected concentration-dependent inhibition of [ 3 H]5-HT uptake with 500 μM MDMA totally blocking transport. Western immunoblotting for microtubule associated protein light chain 3 (LC3) revealed autophagosome formation after treatment with MDMA. Confocal analyses and immunocytochemistry for 5-HT, Hoechst and LC3 confirmed MDMA induced autophagy with abundant LC3-positive puncta within 5-HT neurons. Rilmenidine (1 μM) protected against MDMA-induced injury and image analysis showed full preservation of 5-HT arbours. MDMA had no effect on GABA neurons, indicating specificity of action at 5-HT neurons. MDMA-induced neurotoxicity involves autophagy induction in 5-HT neurons, and rilmenidine via beneficial actions against toxic intracellular events represents a potential treatment for its pathobiology in sustained usage. Copyright © 2017 Elsevier Ltd. All rights reserved.

MDMA ("ecstasy") abuse as an example of dopamine neuroplasticity.

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Schenk, Susan

2011-04-01

A number of reviews have focused on the short- and long-term effects of MDMA and, in particular, on the persistent deficits in serotonin neurotransmission that accompany some exposure regimens. The mechanisms underlying the serotonin deficits and their relevance to various behavioral and cognitive consequences of MDMA use are still being debated. It has become clear, however, that some individuals develop compulsive and uncontrolled drug-taking that is consistent with abuse. For other drugs of abuse, this transition has been attributed to neuroadaptations in central dopamine mechanisms that occur as a function of repeated drug exposure. A question remains as to whether similar neuroadaptations occur as a function of exposure to MDMA and the impact of serotonin neurotoxicity in the transition from use to abuse. This review focuses specifically on this issue by first providing an overview of human studies and then reviewing the animal literature with specific emphasis on paradigms that measure subjective effects of drugs and self-administration as indices of abuse liability. It is suggested that serotonin deficits resulting from repeated exposure to MDMA self-administration lead to a sensitized dopaminergic response to the drug and that this sensitized response renders MDMA comparable to other drugs of abuse. Copyright © 2010 Elsevier Ltd. All rights reserved.

The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

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Sandra Montagud-Romero

Full Text Available The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype.

MDMA does not alter responses to the Trier Social Stress Test in humans.

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Bershad, Anya K; Miller, Melissa A; de Wit, Harriet

2017-07-01

±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested. In this study, we sought to test the effects of MDMA on responses to stress in healthy adults using a public speaking task. We hypothesized that the drug would reduce responses to the stressful task. Volunteers (N = 39) were randomly assigned to receive placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a stress and a no-stress session. Dependent measures included subjective reports of drug effects and emotional responses to the task, as well as salivary cortisol, heart rate, and blood pressure. The stress task produced its expected increase in physiological responses (cortisol, heart rate) and subjective ratings of stress in all three groups, and MDMA produced its expected subjective and physiological effects. MDMA alone increased ratings of subjective stress, heart rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did not moderate responses to the Trier Social Stress Test. Despite its efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or objective responses to stress in this controlled study. The conditions under which MDMA relieves responses to negative events or memories remain to be determined.

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

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Drew J. Puxty

2017-07-01

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

Direct and indirect cardiovascular actions of cathinone and MDMA in the anaesthetized rat.

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Alsufyani, Hadeel A; Docherty, James R

2015-07-05

The stimulants cathinone (from Khat leaves) and methylenedioxymeth-amphetamine (MDMA) produce adrenoceptor mediated tachycardia and vasopressor actions that may be the result of direct receptor stimulation, actions on the noradrenaline transporter, and/or displacement of noradrenaline from nerve terminals. Effects of cathinone or MDMA were compared with those of the indirect sympathomimetic tyramine. Male Wistar rats were anaesthetized with pentobarbitone for blood pressure and heart rate recording. Some rats were sympathectomised by treatment with 6-hydroxydopamine. In the anaesthetised rat, cathinone, MDMA and tyramine (all 0.001-1 mg/kg) produced marked tachycardia, tyramine produced marked pressor responses and MDMA produced small pressor responses. The tachycardia to cathinone and MDMA was almost abolished by propranolol (1mg/kg). Pretreatment with cocaine (1mg/kg) did not significantly affect the tachycardia to cathinone or MDMA, but reduced the response to tyramine. However, in sympathectomised rats, the tachycardia to cathinone or MDMA was markedly attenuated, but the tachycardia to tyramine was only partially reduced. Blood pressure effects of tyramine and MDMA were also markedly attenuated by sympathectomy. The results demonstrate firstly that cocaine may not be the most suitable agent for assessing direct versus indirect agonism in cardiovascular studies. Secondly, the use of chemical sympathectomy achieved the desired goal of demonstrating that cardiac β-adrenoceptor mediated actions of cathinone and MDMA are probably largely indirect. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebral (1)H MRS alterations in recreational 3, 4-methylenedioxymethamphetamine (MDMA, "ecstasy") users.

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Chang, L; Ernst, T; Grob, C S; Poland, R E

1999-10-01

3,4-methylenedioxymethamphetamine (MDMA) is an illicit drug that has been associated with serotonergic axonal degeneration in animals. This study evaluates neurochemical abnormalities in recreational MDMA users. Twenty-two MDMA users and 37 normal subjects were evaluated with magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) in the mid-frontal, mid-occipital, and parietal brain regions. (1)H MRS showed normal N-acetyl (NA) compounds in all brain regions. The myo-inositol (MI) concentration (+16.3%, P = 0.04) and the MI to creatine (CR) ratio (+14.1%, P = 0. 01) were increased in the parietal white matter of MDMA users. The cumulative lifetime MDMA dose showed significant effects on [MI] in the parietal white matter and the occipital cortex. The normal NA concentration suggests a lack of significant neuronal injury in recreational MDMA users. However, the usage-related increase in MI suggests that exposure to MDMA, even at recreational doses, may cause increased glial content. J. Magn. Reson. Imaging 1999;10:521-526. Copyright 1999 Wiley-Liss, Inc.

Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes

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Pontes, Helena; Sousa, Carla; Silva, Renata; Fernandes, Eduarda; Carmo, Helena; Remiao, Fernando; Carvalho, Felix; Bastos, Maria Lourdes

2008-01-01

Ethanol is frequently consumed along with 3,4-methylenedioxymethamphetamine (MDMA; ecstasy). Since both compounds are hepatotoxic and are metabolized in the liver, an increased deleterious interaction resulting from the concomitant use of these two drugs seems plausible. Another important feature of MDMA-induced toxicity is hyperthermia, an effect known to be potentiated after continuous exposure to ethanol. Considering the potential deleterious interaction, the aim of the present study was to evaluate the hepatotoxic effects of ethanol and MDMA mixtures to primary cultured rat hepatocytes and to elucidate the mechanism(s) underlying this interaction. For this purpose, the toxicity induced by MDMA to primary cultured rat hepatocytes in absence or in presence of ethanol was evaluated, under normothermic (36.5 deg. C) and hyperthermic (40.5 deg. C) conditions. While MDMA and ethanol, by themselves, had discrete effects on the analysed parameters, which were slightly aggravated under hyperthermia, the simultaneous incubation of MDMA and ethanol for 24 h, resulted in high cell death ratios accompanied by a significant disturbance of cellular redox status and decreased energy levels. Evaluation of apoptotic/necrotic features provided clear evidences that the cell death occurs preferentially through a necrotic pathway. All the evaluated parameters were dramatically aggravated when cells were incubated under hyperthermia. In conclusion, co-exposure of hepatocytes to ethanol and MDMA definitely results in a synergism of the hepatotoxic effects, through a disruption of the cellular redox status and enhanced cell death by a necrotic pathway in a temperature-dependent extent

Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss in rats.

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Durkin, Sarah; Prendergast, Alison; Harkin, Andrew

2008-12-12

Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern associated with recreational use of the substituted amphetamine 3,4 methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic considering that psychiatric disorders such as depression and anxiety and responses to first line treatments for these disorders are associated with 5-HT. In this study the effects of prior exposure to MDMA on behavioural and central neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and antidepressant fluoxetine were examined in rats. Animals were administered MDMA (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine treatment groups received either acute (saline injections for 20 days followed by 3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days) drug administration. Prior exposure to MDMA resulted in an attenuation of fluoxetine-induced swimming behaviour in the modified forced swimming test (FST); a behavioural test of antidepressant action. In parallel MDMA treatment resulted in significant regional depletions of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [3H] paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss was enhanced in animals following chronic fluoxetine administration. Elimination of fluoxetine and its metabolite norfluoxetine from the brain abolished this interaction between MDMA and fluoxetine treatment. Fluoxetine administration reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in animals pre-treated with MDMA. Overall the results show that MDMA induces long-term 5-HT loss in the rodent brain and consequently diminishes behaviour and reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These results have potential clinical relevance

Evidence for chronically altered cortical serotonin function in human female recreational ecstasy (MDMA) polydrug users

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Di Iorio, Christina R; Watkins, Tristan J; Dietrich, Mary S; Cao, Aize; Blackford, Jennifer U; Rogers, Baxter; Ansari, Mohammed S; Baldwin, Ronald M; Li, Rui; Kessler, Robert M; Salomon, Ronald M; Benningfield, Margaret; Cowan, Ronald L

2012-01-01

Context MDMA (ecstasy) is a popular recreational drug that produces loss of serotonin (5-HT) axons in animal models. Whether MDMA produces chronic reductions in 5-HT signaling in humans remains controversial. Objective To determine if MDMA use is associated with chronic reductions in serotonin signaling in female human cerebral cortex as reflected by increased 5-HT2A receptors. Design Cross sectional case-control study comparing 5-HT2A receptor levels in abstinent female MDMA polydrug users to MDMA-naive females; within-group design assessing the association of lifetime MDMA use and 5-HT2A receptors. Subjects had at least 90 days abstinence from MDMA use as verified by hair sampling. Cortical 5-HT2A receptor levels were assayed with the 5HT2A-specific Positron Emission Tomography (PET) radioligand [18F]setoperone. Setting Academic Medical Center Research Laboratory. Participants Volunteer female MDMA users (N=14) and MDMA-naive controls (N=10). Main exclusion criteria were non-drug-related DSM-IV axis I psychiatric disorders and general medical illness. Main Outcome Measure Cortical 5-HT2A receptor non-displaceable binding potential (5-HT2ABPND). Results MDMA users had increased 5-HT2ABPND in occipital-parietal (19.7%), temporal (20.5%), occipito-temporal-parietal (18.3%), frontal (16.6%), and fronto-parietal (18.5%) regions (pMDMA use associated positively with 5-HT2ABPND in fronto-parietal (β=0.665;p=0.007), occipito-temporal (β=0.798;p=0.002), fronto-limbic (β=0.634;p=0.024), and frontal (β=0.691;p=0.008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on 5-HT2ABPND. Conclusions Human recreational MDMA use is associated with long-lasting increases in 5-HT2A receptor density. 5-HT2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA produces

Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

OpenAIRE

Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

2016-01-01

3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

Making a medicine out of MDMA.

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Sessa, Ben; Nutt, David

2015-01-01

From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised as a drug with therapeutic potential. Research on its clinical utility stopped when it entered the recreational drug scene but has slowly resurrected in the past decade. Currently there is enough evidence for MDMA to be removed from its Schedule 1 status of 'no medical use' and moved into Schedule 2 (alongside other misused but useful medicines such as heroin and amphetamine). Such a regulatory move would liberate its use as a medicine for patients experiencing severe mental illnesses such as treatment-resistant post-traumatic stress disorder. Royal College of Psychiatrists.

Strenuous exercise aggravates MDMA-induced skeletal muscle damage in mice

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Duarte, Jose A.; Leao, Anabela; Magalhaes, Jose; Ascensao, Antonio; Bastos, Maria L.; Amado, Francisco L.; Vilarinho, Laura; Quelhas, Dulce; Appell, Hans J.; Carvalho, Felix

2005-01-01

The aim of this study was to investigate the influence of ecstasy (MDMA) administration on body temperature and soleus muscle histology in exercised and non-exercised mice. Charles-River mice were distributed into four groups: Control (C), exercise (EX), MDMA treated (M), and M + EX. The treated animals received an i.p. injection (10 mg/kg) of MDMA (saline for C and EX), and the exercise consisted of a 90 min level run at a velocity of 900 m/h, immediately after the MDMA or saline administration. Body temperature was recorded every 30 min via subcutaneous implanted transponder. Animals were sacrificed 1.5, 25.5, and 49.5 h after i.p. injection and the soleus muscles were removed and processed for light and electron microscopy. The MDMA-treated animals showed a significant increase in body temperature (similar in M and M + EX groups), reaching the peak 90 min after i.p. administration; their temperature remained higher than control for more than 5 h. The EX group evidenced a similar and parallel, yet lower temperature increase during exercise and recovery. Morphological signs of damage were rarely encountered in the EX group; they were more pronounced in M group and even aggravated in M + EX group. In conclusion, MDMA and exercise per se increased body temperature but in conjunction did not have a cumulated effect. However, ecstasy and concomitant physical activity might severely accumulate with regard to skeletal muscle toxicity and may lead to rhabdomyolysis

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

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

2010-01-01

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

Protection against MDMA-induced dopaminergic neurotoxicity in mice by methyllycaconitine: involvement of nicotinic receptors.

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Chipana, C; Camarasa, J; Pubill, D; Escubedo, E

2006-09-01

Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. Previous studies demonstrated the participation of alpha-7 nicotinic receptors (nAChR) in the neurotoxic effect of methamphetamine. The aim of this paper was to study the role of this receptor type in the acute effects and neurotoxicity of MDMA in mice. In vivo, methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at dopaminergic but not at serotonergic level, without affecting MDMA-induced hyperthermia. Glial activation was also fully prevented by MLA. In vitro, MDMA induced intrasynaptosomal reactive oxygen species (ROS) generation, which was calcium-, nitric-oxide synthase-, and protein kinase C-dependent. Also, the increase in ROS was prevented by MLA and alpha-bungarotoxin. Experiments with reserpine point to endogenous dopamine (DA) as the main source of MDMA-induced ROS. MLA also brought the MDMA-induced inhibition of [3H]DA uptake down, from 73% to 11%. We demonstrate that a coordinated activation of alpha-7 nAChR, blockade of DA transporter function and displacement of DA from intracellular stores induced by MDMA produces a neurotoxic effect that can be prevented by MLA, suggesting that alpha-7 nAChR have a key role in the MDMA neurotoxicity in mice; however, the involvement of nicotinic receptors containing the beta2 subunit cannot be conclusively ruled out.

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

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

2016-02-01

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

Release of [3H]-monoamines from superfused rat striatal slices by methylenedioxymethamphetamine (MDMA)

International Nuclear Information System (INIS)

Levin, J.A.; Schmidt, C.J.; Lovenberg, W.

1986-01-01

MDMA is a phenylisopropylamine which is reported to have unique behavioral effects in man. Because of its structural similarities to the amphetamines the authors have compared the effects of MDMA and two related amphetamines on the spontaneous release of tritiated dopamine (DA) and serotonin (5HT) from superfused rat striatal slices. At concentrations of 10 -7 - 10 -5 M MDMA and the serotonergic neurotoxin, p-chloroamphetamine, were equipotent releasers of [ 3 H]5HT being approximately 10x more potent than methamphetamine. However, methamphetamine was the more potent releaser of [ 3 H]DA by a factor of approximately 10x. MDMA-induced release of both [ 5 H]5HT and [ 3 H]DA was Ca 2+ -independent and inhibited by selective monoamine uptake blockers suggesting a carrier-dependent release mechanism. Synaptosomal uptake experiments with (+)[ 3 H]MDMA indicated no specific uptake of the drug further suggesting the effect of uptake blockers may be to inhibit the carrier-mediated export of amines displaced by MDMA

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).

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Young, Matthew B; Norrholm, Seth D; Khoury, Lara M; Jovanovic, Tanja; Rauch, Sheila A M; Reiff, Collin M; Dunlop, Boadie W; Rothbaum, Barbara O; Howell, Leonard L

2017-10-01

3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT 2A -mediated behavior, and 5-HT 2A antagonism disrupted MDMA's effect on extinction. We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT 2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

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

Directory of Open Access Journals (Sweden)

Una D. McCann

2007-01-01

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

Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice.

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Viñals, Xavier; Maldonado, Rafael; Robledo, Patricia

2013-03-01

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non-neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and attentional set-shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5 days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in the saccharin preference test under similar experimental conditions. Correct responding on delayed alternation was increased 1 day after repeated treatment with MDMA (30 mg/kg), probably because of general behavioural quiescence. Notably, the high dose regimen of MDMA impaired attentional set-shifting related to an increase in total perseveration errors. Finally, basal extracellular levels of DA in the striatum were not modified in mice repeatedly treated with MDMA with respect to controls. However, an acute challenge with MDMA (10 mg/kg) failed to increase DA outflow in mice receiving the highest MDMA dose (30 mg/kg), corroborating a decrease in the functionality of DA transporters. Seven days after this treatment, the effects of MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic doses of MDMA produce lasting impairments in recall of alternation behaviour and reduce cognitive flexibility in mice. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

MDMA enhances "mind reading" of positive emotions and impairs "mind reading" of negative emotions.

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Hysek, Cédric M; Domes, Gregor; Liechti, Matthias E

2012-07-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) increases sociability. The prosocial effects of MDMA may result from the release of the "social hormone" oxytocin and associated alterations in the processing of socioemotional stimuli. We investigated the effects of MDMA (125 mg) on the ability to infer the mental states of others from social cues of the eye region in the Reading the Mind in the Eyes Test. The study included 48 healthy volunteers (24 men, 24 women) and used a double-blind, placebo-controlled, within-subjects design. A choice reaction time test was used to exclude impairments in psychomotor function. We also measured circulating oxytocin and cortisol levels and subjective drug effects. MDMA differentially affected mind reading depending on the emotional valence of the stimuli. MDMA enhanced the accuracy of mental state decoding for positive stimuli (e.g., friendly), impaired mind reading for negative stimuli (e.g., hostile), and had no effect on mind reading for neutral stimuli (e.g., reflective). MDMA did not affect psychomotor performance, increased circulating oxytocin and cortisol levels, and produced subjective prosocial effects, including feelings of being more open, talkative, and closer to others. The shift in the ability to correctly read socioemotional information toward stimuli associated with positive emotional valence, together with the prosocial feelings elicited by MDMA, may enhance social approach behavior and sociability when MDMA is used recreationally and facilitate therapeutic relationships in MDMA-assisted psychotherapeutic settings.

MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults.

Science.gov (United States)

Danforth, Alicia L; Struble, Christopher M; Yazar-Klosinski, Berra; Grob, Charles S

2016-01-04

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

2002-09-01

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.

MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?

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Feduccia, Allison A; Mithoefer, Michael C

2018-06-08

MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers. This review explores the potential role of memory reconsolidation and fear extinction during MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin, norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By reducing activation in brain regions implicated in the expression of fear- and anxiety-related behaviors, namely the amygdala and insula, and increasing connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing of traumatic memories and emotional engagement with therapeutic processes. Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

MDMA ("Ecstasy") and its association with cerebrovascular accidents: preliminary findings

NARCIS (Netherlands)

Reneman, L.; Habraken, J. B.; Majoie, C. B.; Booij, J.; den Heeten, G. J.

2000-01-01

BACKGROUND AND PURPOSE: Abuse of the popular recreational drug "Ecstasy" (MDMA) has been linked to the occurrence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT(2) receptors play a role in the regulation of brain

Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.

Science.gov (United States)

Kuypers, Kim Pc; Dolder, Patrick C; Ramaekers, Johannes G; Liechti, Matthias E

2017-05-01

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

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

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Dina Popova

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

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

Science.gov (United States)

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

2016-01-01

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

MDMA (ecstasy/molly) use among African Americans: The perceived influence of hip-hop/rap music.

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Rigg, Khary K; Estreet, Anthony T

2018-02-12

Over the past two decades, the demographic profile of MDMA (ecstasy/molly) users has changed. In particular, African American MDMA use has risen in some cities. One explanation of this new trend is the drug's recent popularity (as molly) in hip-hop/rap (HHR) music. Several top rappers endorse the drug as a way to have fun or get women "loose." There are currently no studies, however, that investigate the extent to which African American MDMA users listen to HHR music or the influence that these pro-MDMA messages have on their use of the drug. To address this gap, the current study used survey data to (a) identify the extent to which HHR music is listened to by African American MDMA users and (b) assess the perceived influence of HHR music on their decision to begin using. Qualitative interview data are also presented to contextualize the influence of these messages on their use of MDMA. The findings of this study suggest that African American MDMA users are high consumers of HHR music and that pro-MDMA messages in HHR music are influencing their expectations of the drug and their decision to initiate use. These findings add to the limited amount of research on African American MDMA use and have the potential to inform future interventions.

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

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Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

2016-01-01

MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

Behavioral Effects and Pharmacokinetics of (±)-3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) after Intragastric Administration to Baboons

OpenAIRE

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

2013-01-01

(±)-3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.32–7.8 mg/kg) were administered via an intragastric catheter to adult male baboons (N = 4). Effects of MDMA on food-maintained responding were assessed over a 20-hour period, whereas untrained behaviors...

Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex.

Science.gov (United States)

Hysek, Cédric M; Liechti, Matthias E

2012-12-01

Pupillometry can be used to characterize autonomic drug effects. This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function. Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo-MDMA (125 mg), placebo-placebo, pretreatment-placebo, or pretreatment-MDMA using a crossover design. MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function. The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration-time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.

Nonlinear Pharmacokinetics of (±)3,4-Methylenedioxymethamphetamine (MDMA) and Its Pharmacodynamic Consequences in the Rat

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Concheiro, Marta; Baumann, Michael H.; Scheidweiler, Karl B.; Rothman, Richard B.; Marrone, Gina F.

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA’s safety are needed. We evaluated MDMA’s pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (±)-3,4-dihydroxymethamphetamine (HHMA), (±)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (±)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography–tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 ± 47.1 ng/ml, HHMA and HMMA were major metabolites, and MDMA was metabolized to MDA. After 5- and 10-mg/kg doses, MDMA areas under the curve (AUCs) were 3- and 10-fold greater than those after 2.5 mg/kg; HHMA and HMMA AUC values were relatively constant across doses; and MDA AUC values were greater than dose-proportional. Our data provide decisive in vivo evidence that MDMA and MDA display nonlinear accumulation via metabolic autoinhibition in the rat. Importantly, 5-HT syndrome severity correlated with MDMA concentrations (r = 0.8083; P MDMA’s behavioral and hyperthermic effects may involve distinct mechanisms. Given key similarities between MDMA pharmacokinetics in rats and humans, data from rats can be useful when provided at clinically relevant doses. PMID:24141857

Cognitive and behavioural effects induced by social stress plus MDMA administration in mice.

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García-Pardo, M P; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

2017-02-15

Adverse life experiences such as social stress may make an individual more vulnerable to drug addiction and mental disorders associated with drug consumption. The present work aimed to evaluate the effects of stress induced by acute social defeat combined with the administration of 3,4-methylenedioxymethamphetamine (MDMA) on depression-like behaviour, memory function and motor response to drug in late adolescent male mice. Two groups of mice were exposed to social defeat (SD) during four encounters with an aggressive co-specific, which took place on alternate days. Immediately after defeat, animals were treated with saline or MDMA 10mg/kg (SD+SAL and SD+MDMA). In control groups, mice were placed in a neutral cage without an opponent (Control+SAL, Control+MDMA). Corticosterone levels and temperature were measured on the last day of this phase. During the following days, the behaviour of the animals was evaluated in the tail suspension test (an animal model of depression), memory tasks (passive avoidance and object recognition) and, after administration of 5mg/kg of MDMA, in the open-field test. Exposure of adult mice to acute social defeat plus MDMA increased immobility in the tail suspension test (depression-like behaviour), produced cognitive impairment, and reduced the motor response to MDMA. An increase in corticosterone levels and a decrease of temperature were also observed. As hypothesised, a combination of social stress and consumption of MDMA increases the risk of developing mental and cognitive disorders. Our results support the idea that stress is a common contributing factor to the high rate of comorbidity between substance abuse and mental disease. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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

2015-11-01

MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA's acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy. MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10- or 35-day MDMA, or daily 10-day MDMA followed by 25-day saline washout (10 + 25 days). MDMA treatment caused differential gene expression (p 1.5) in 752 genes following 10 days, 558 genes following 35 days, and 113 genes following 10-day MDMA + 25-day saline washout. Changes in MAPK and circadian rhythm gene expression were identified as early as 10 days. After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was found to be 71% at 10 days, 68% at 35 days, and 91% at 10 + 25 days washout. Differential gene expression paralleled DNA methylation in 22% of genes at 10-day treatment, 17% at 35 days, and 48% at 10 + 25 days washout. We show here that MDMA induced cardiac epigenetic changes in DNA methylation where hypermethylation predominated. Moreover, MDMA induced gene expression of key elements of circadian rhythm regulatory genes. This suggests a fundamental organism-level event to explain some of the etiologies of MDMA dysfunction in the heart. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

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Lamers, C T J; Ramaekers, J G; Muntjewerff, N D; Sikkema, K L; Samyn, N; Read, N L; Brookhuis, K A; Riedel, W J

2003-12-01

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

Effects of MDMA on blood glucose levels and brain glucose metabolism

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Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

2007-06-15

This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

Effects of MDMA on blood glucose levels and brain glucose metabolism

International Nuclear Information System (INIS)

Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M.; Arango, C.; Ricaurte, G.

2007-01-01

This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

Role of nitric oxide pathway in the conditioned rewarding effects of MDMA in mice.

Science.gov (United States)

García-Pardo, M P; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

2017-07-14

It is estimated that 2.1 million young adults used MDMA/Ecstasy in the last year in Europe. Vulnerable subjects can develop dependence after MDMA abuse but currently there does not exist an effective treatment for this disorder. The nitric oxide (NO) pathway seems to have an important role on the rewarding effects of different drugs and has been proposed as a new pharmacological treatment for psychostimulant addiction. In the present study, we intend to evaluate whether the blockade of the NO synthesis (NOS) interferes with the rewarding effects of MDMA in the conditioned preference place (CPP) paradigm in young adult male mice. Our results indicated that mice treated with 7-nitroindazole (a NOS inhibitor) did not show CPP after conditioning with MDMA (1.25mg/kg). These results demonstrated the role of the NO pathway in the rewarding effects of MDMA and suggested that the manipulation of this pathway could be a new therapeutic option for MDMA abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

MDMA enhances hippocampal-dependent learning and memory under restrictive conditions, and modifies hippocampal spine density.

Science.gov (United States)

Abad, Sònia; Fole, Alberto; del Olmo, Nuria; Pubill, David; Pallàs, Mercè; Junyent, Fèlix; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena

2014-03-01

Addictive drugs produce forms of structural plasticity in the nucleus accumbens and prefrontal cortex. The aim of this study was to investigate the impact of chronic MDMA exposure on pyramidal neurons in the CA1 region of hippocampus and drug-related spatial learning and memory changes. Adolescent rats were exposed to saline or MDMA in a regime that mimicked chronic administration. One week later, when acquisition or reference memory was evaluated in a standard Morris water maze (MWM), no differences were obtained between groups. However, MDMA-exposed animals performed better when the MWM was implemented under more difficult conditions. Animals of MDMA group were less anxious and were more prepared to take risks, as in the open field test they ventured more frequently into the central area. We have demonstrated that MDMA caused an increase in brain-derived neurotrophic factor (BDNF) expression. When spine density was evaluated, MDMA-treated rats presented a reduced density when compared with saline, but overall, training increased the total number of spines, concluding that in MDMA-group, training prevented a reduction in spine density or induced its recovery. This study provides support for the conclusion that binge administration of MDMA, known to be associated to neurotoxic damage of hippocampal serotonergic terminals, increases BDNF expression and stimulates synaptic plasticity when associated with training. In these conditions, adolescent rats perform better in a more difficult water maze task under restricted conditions of learning and memory. The effect on this task could be modulated by other behavioural changes provoked by MDMA.

The combined effects of 3,4-methylenedioxymethamphetamine (MDMA) and selected substituted methcathinones on measures of neurotoxicity.

Science.gov (United States)

Miner, Nicholas B; O'Callaghan, James P; Phillips, Tamara J; Janowsky, Aaron

2017-05-01

The rise in popularity of substituted methcathinones (aka "bath salts") has increased the focus on their neurotoxic effects. Two commonly abused methcathinones, 3,4-methylenedioxymethcathinone (methylone, MDMC) and 3,4-methylenedioxypyrovalerone (MDPV), are often concomitantly ingested with the illicit drug 3,4-methylenedioxymethamphetamine (MDMA). To examine potential neurotoxic effects of these drug combinations, C57BL/6J mice were administered 4 i.p. injection of the drugs, at 2h intervals, either singularly: MDMA 15 or 30mg/kg, methylone 20mg/kg, MDPV 1mg/kg; or in combination: methylone/MDMA 20/15mg/kg, MDPV/MDMA 1/15mg/kg. Drug effects on thermoregulation were characterized and striatal tissue analyzed after 2 or 7days for dopamine (DA) and tyrosine hydroxylase (TH) levels, as well as glial fibrillary acidic protein (GFAP) expression. Two days following drug administration, DA and TH were decreased only in the MDMA 30mg/kg group, whereas GFAP expression was dose-dependently increased by MDMA alone. While the combination of the methcathinones with the lower MDMA dose did not affect DA or TH levels, both blocked the MDMA-induced increase in GFAP expression. Seven days following drug administration, there were no significant differences in DA, TH, or GFAP for any treatment group, indicating that changes in DA, TH, and GFAP were transient. Five of the six drug groups exhibited acute hypothermia followed by gradually increasing temperatures. Animals treated with MDPV did not exhibit these biphasic temperature changes, and resembled the saline group. These results indicate that specific effects of both methylone and MDPV on DA depletion or astrocyte activation in the striatum are not additive with effects of MDMA, but block astrogliosis caused by MDMA alone. Additionally, MDPV modulates thermoregulation through a different mechanism than methylone or MDMA. Published by Elsevier Inc.

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

NARCIS (Netherlands)

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

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

Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes.

Science.gov (United States)

Madry, Milena M; Steuer, Andrea E; Hysek, Cédric M; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas

2016-01-01

Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9-77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-L-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2-2.4 for MDMA and 0.85-0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044-0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable.

Occipital cortical proton MRS at 4 Tesla in human moderate MDMA polydrug users

OpenAIRE

Cowan, Ronald L.; Bolo, Nicolas R.; Dietrich, Mary; Haga, Erica; Lukas, Scott E.; Renshaw, Perry F.

2007-01-01

The recreational drug MDMA (3,4, methylenedioxymethamphetamine; sold under the street name of Ecstasy) is toxic to serotonergic axons in some animal models of MDMA administration. In humans, MDMA use is associated with alterations in markers of brain function that are pronounced in occipital cortex. Among neuroimaging methods, magnetic resonance spectroscopy (MRS) studies of brain metabolites N-acetylaspartate (NAA) and myoinositol (MI) at a field strength of 1.5 Tesla (T) reveal inconsistent...

Ecstasy (MDMA) and oral health

NARCIS (Netherlands)

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

2008-01-01

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

Motivations for Using MDMA (Ecstasy/Molly) among African Americans: Implications for Prevention and Harm-Reduction Programs.

Science.gov (United States)

Rigg, Khary K

2017-01-01

Despite the growing popularity of MDMA (ecstasy/molly) among African Americans, their motives for using the drug are still largely unknown. The purpose of this study was to identify and describe the most salient motivations for using MDMA among this understudied population. In-depth interviews (n = 15) were conducted with a sample of African American young adults in Southwest Florida between August 2014 and November 2015. The primary motivations for using MDMA included: (1) altering the effects of marijuana and alcohol; (2) lasting longer sexually; (3) enhancing sexual pleasure; and (4) facilitating "freaky" sexual experiences. This is the first study to directly examine MDMA motivations specifically among African American drug users, and findings shed light on why some African Americans use MDMA. A better understanding of why African Americans use this drug should help to inform prevention and harm-reduction efforts. Study findings show the need for health messages that include the potential consequences of mixing MDMA with other drugs, and engaging in high-risk sexual behaviors after taking MDMA. These data contrast with motivations (e.g., introspection, self-enlightenment, getting into the music) commonly reported among groups of largely White MDMA users, suggesting that interventions tailored specifically for African American users are needed.

Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat†

Science.gov (United States)

Perrine, Shane A.; Michaels, Mark S.; Ghoddoussi, Farhad; Hyde, Elisabeth M.; Tancer, Manuel E.; Galloway, Matthew P.

2010-01-01

Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected. High resolution magic angle spinning proton magnetic resonance spectroscopy (1H-MRS) at 11.7 T, a specialized version of MRS aptly suited for analysis of semi-solid materials such as intact tissue samples, was used to measure the cardiac metabolomic profile, including alanine, lactate, succinate, creatine, and carnitine, in heart tissue from rats treated with MDMA. MDMA effects on MR-visible choline, glutamate, glutamine, and taurine were also determined. Body temperature was measured following each MDMA administration and serotonin and norepinephrine (NE) levels were measured by high pressure liquid chromatography (HPLC) in heart tissue from treated animals. MDMA significantly and dose-dependently increased body temperature, a hallmark of amphetamines. Serotonin, but not NE, levels were significantly and dose-dependently decreased by MDMA in the heart wall. MDMA significantly altered the MR-visible profile with an increase in carnitine and no change in other key compounds involved in cardiomyocyte energy metabolomics. Finally, choline levels were significantly decreased by MDMA in heart. The results are consistent with the notion that MDMA has significant effects on cardiovascular serotonergic tone and disrupts the metabolic homeostasis of energy regulation in cardiac tissue, potentially increasing utilization of fatty acid metabolism. The contributions of serotonergic

Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat.

Science.gov (United States)

Perrine, Shane A; Michaels, Mark S; Ghoddoussi, Farhad; Hyde, Elisabeth M; Tancer, Manuel E; Galloway, Matthew P

2009-05-01

Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected. High resolution magic angle spinning proton magnetic resonance spectroscopy ((1)H-MRS) at 11.7 T, a specialized version of MRS aptly suited for analysis of semi-solid materials such as intact tissue samples, was used to measure the cardiac metabolomic profile, including alanine, lactate, succinate, creatine, and carnitine, in heart tissue from rats treated with MDMA. MDMA effects on MR-visible choline, glutamate, glutamine, and taurine were also determined. Body temperature was measured following each MDMA administration and serotonin and norepinephrine (NE) levels were measured by high pressure liquid chromatography (HPLC) in heart tissue from treated animals. MDMA significantly and dose-dependently increased body temperature, a hallmark of amphetamines. Serotonin, but not NE, levels were significantly and dose-dependently decreased by MDMA in the heart wall. MDMA significantly altered the MR-visible profile with an increase in carnitine and no change in other key compounds involved in cardiomyocyte energy metabolomics. Finally, choline levels were significantly decreased by MDMA in heart. The results are consistent with the notion that MDMA has significant effects on cardiovascular serotonergic tone and disrupts the metabolic homeostasis of energy regulation in cardiac tissue, potentially increasing utilization of fatty acid metabolism. The contributions of serotonergic

The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences

International Nuclear Information System (INIS)

Wyeth, Richard P.; Mills, Edward M.; Ullman, Alison; Kenaston, M. Alexander; Burwell, Johanna; Sprague, Jon E.

2009-01-01

Female subjects have been reported to be less sensitive to the hyperthermic effects of 3,4-methylenedioxymethamine (MDMA) than males. Studies were designed to examine the cellular mechanisms involved in these sex sensitive differences. Gonadectomized female and male rats were treated with a 200 μg 100 μL -1 of estrogen or 100 μg 100 μL -1 of testosterone respectively every 5 days for a total of three doses. Rats were then challenged with either saline or MDMA (20 mg kg -1 , sc). Rats were then euthanized and aortas were constricted, in vitro, by serial phenylephrine (Phe) addition with or without the inhibitor of nitric oxide (NO) synthase, g-nitro-L-Arginine-Methyl Ester (L-NAME). Skeletal muscle uncoupling protein-3 (UCP3) expression was measured as well as plasma norepinephrine (NE) levels. All males but no females developed hyperthermia following MDMA treatment. The EC 50 for Phe dose response curves increased only in the females treated with MDMA and T max for Phe increased following L-NAME only in the females. Both males and females demonstrated an increase in plasma NE following MDMA treatment; however, males displayed a significantly greater NE concentration. Skeletal muscle UCP3 expression was 80% less in females than in males. These results suggest that the inability of MDMA to induce a thermogenic response in the female subjects may be due to four sex-specific mechanisms: 1) Female subjects have reduced sympathetic activation following MDMA challenge; 2) Female vasculature is less sensitive to α 1 -AR stimulation following MDMA challenge; 3) Female vasculature has an increased sensitivity to NO; 4) UCP3 expression in skeletal muscle is less in females

Variations in management of mild prenatal hydronephrosis among maternal-fetal medicine obstetricians, and pediatric urologists and radiologists.

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Zanetta, Vitor C; Rosman, Brian M; Bromley, Bryan; Shipp, Thomas D; Chow, Jeanne S; Campbell, Jeffrey B; Herndon, C D Anthony; Passerotti, Carlo C; Cendron, Marc; Retik, Alan B; Nguyen, Hiep T

2012-11-01

There are no current guidelines for diagnosing and managing mild prenatal hydronephrosis. Variations in physician approach make it difficult to analyze outcomes and establish optimal management. We determined the variability of diagnostic approach and management regarding prenatal hydronephrosis among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. Online surveys were sent to mailing lists for national societies for each specialty. Participants were surveyed regarding criteria for diagnosing mild prenatal hydronephrosis and recommendations for postnatal management, including use of antibiotic prophylaxis, followup scheduling and type of followup imaging. A total of 308 maternal-fetal medicine obstetricians, 126 pediatric urologists and 112 pediatric radiologists responded. Pediatric urologists and radiologists were divided between Society for Fetal Urology criteria and use of anteroposterior pelvic diameter for diagnosis, while maternal-fetal medicine obstetricians preferred using the latter. For postnatal evaluation radiologists preferred using personal criteria, while urologists preferred using anteroposterior pelvic diameter or Society for Fetal Urology grading system. There was wide variation in the use of antibiotic prophylaxis among pediatric urologists. Regarding the use of voiding cystourethrography/radionuclide cystography in patients with prenatal hydronephrosis, neither urologists nor radiologists were consistent in their recommendations. Finally, there was no agreement on length of followup for mild prenatal hydronephrosis. We observed a lack of uniformity regarding grading criteria in diagnosing hydronephrosis prenatally and postnatally among maternal-fetal medicine obstetricians, pediatric urologists and pediatric radiologists. There was also a lack of agreement on the management of mild intermittent prenatal hydronephrosis, resulting in these cases being managed inconsistently. A unified set of guidelines for

A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

Science.gov (United States)

Harper, David N; Langen, Anna-Lena; Schenk, Susan

2014-01-01

Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

MDMA Increases Excitability in the Dentate Gyrus: Role of 5HT2A Receptor Induced PGE2 Signaling

Science.gov (United States)

Collins, Stuart A.; Huff, Courtney; Chiaia, Nicolas; Gudelsky, Gary A.; Yamamoto, Bryan K.

2015-01-01

MDMA is a widely abused psychostimulant which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA. Administration of MDMA into the dentate gyrus of rats increased PGE2 concentrations which was prevented by coadministration of MDL100907, a 5HT2A receptor antagonist. MDMA-induced increases in extracellular glutamate were inhibited by local administration of SC-51089, an inhibitor of the EP1 prostaglandin receptor. Systemic administration of SC-51089 during injections of MDMA prevented the decreases in parvalbumin interneurons observed 10 days later. The loss of parvalbumin immunoreactivity after MDMA exposure coincided with a decrease in paired-pulse inhibition and afterdischarge threshold in the dentate gyrus. These changes were prevented by inhibition of EP1 and 5HT2A receptors during MDMA. Additional experiments revealed an increased susceptibility to kainic acid-induced seizures in MDMA treated rats which could be prevented with SC51089 treatments during MDMA exposure. Overall, these findings suggest that 5HT2A receptors mediate MDMA-induced PGE2 signaling and subsequent increases in glutamate. This signaling mediates parvalbumin cell losses as well as physiologic changes in the dentate gyrus, suggesting that the lack of the inhibition provided by these neurons increases the excitability within the dentate gyrus of MDMA treated rats. PMID:26670377

Prevention of drug priming- and cue-induced reinstatement of MDMA-seeking behaviors by the CB1 cannabinoid receptor antagonist AM251.

Science.gov (United States)

Nawata, Yoko; Kitaichi, Kiyoyuki; Yamamoto, Tsuneyuki

2016-03-01

3,4-Methylenedioxymethamphetamine (MDMA), a methamphetamine (METH) derivative, exhibits METH-like actions at monoamine transporters and positive reinforcing effects in rodents and primates. The purposes of the present study were to determine whether cross-reinstatement would be observed between MDMA and METH and if the cannabinoid receptor, a receptor known to play critical roles in the brain reward system, could modulate MDMA craving. Rats were trained to press a lever for intravenous MDMA (0.3mg/infusion) or METH (0.02mg/infusion) infusions under a fixed ratio 1 schedule paired with drug-associated cues (light and tone). Following drug self-administration acquisition training, rats underwent extinction training (an infusion of saline). Reinstatement tests were performed once the extinction criteria were achieved. In MDMA-trained rats, the MDMA-priming injection (3.2mg/kg, i.p.) or re-exposure to MDMA-associated cues reinstated MDMA-seeking behavior. Additionally, a priming injection of METH (1.0mg/kg, i.p.) also reinstated MDMA-seeking behavior. In contrast, none of the MDMA doses reinstated METH-seeking behavior in the METH-trained rats. The CB1 cannabinoid receptor antagonist AM251 markedly attenuated the MDMA-seeking behaviors induced by MDMA-priming injection or re-exposure to MDMA-associated cues in a dose-dependent manner. These findings show that MDMA has obvious addictive potential for reinstating drug-seeking behavior and that METH can be an effective stimulus for reinstating MDMA-seeking behaviors. Furthermore, based on the attenuating effect of AM251 in the reinstatement of MDMA-seeking behaviors, drugs that suppress CB1 receptors may be used in treatment of MDMA dependence. Copyright © 2016. Published by Elsevier Ireland Ltd.

Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories.

Science.gov (United States)

Skrinska, Victor A; Gock, Susan B

2005-01-01

The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported.

Procedural and declarative memory performance, and the memory consolidation function of sleep, in recent and abstinent Ecstasy/MDMA users

Science.gov (United States)

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

2013-01-01

This study assessed the effects of ecstasy/MDMA on declarative memory (Rivermead Behavioral Memory task - RBMT), on procedural learning (Finger Tapping Task - FTT), and on the memory consolidation function of sleep for these two tasks. Testing occurred in 2 afternoon testing sessions, 24 hours apart so that a full period of sleep was allowed between them. Groups were: Non-drug taking Controls (n=24); Recent Ecstasy/MDMA users, who had taken ecstasy and/or MDMA 2–3 days before the first testing session (n=25), and Abstinent Ecstasy/MDMA users, who had not taken ecstasy/MDMA for at least 8 days before the first session (n=17). The recent ecstasy/MDMA users performed significantly worse than controls on the RBMT (mean recall 76.1% of control group recall), but did not differ from controls on FTT performance. Correspondingly there was a significant regression between the continuous variable of recency of ecstasy/MDMA use and RBMT performance. However, there was an interaction between ecstasy/MDMA use and subsequent other drug use. Controls had similar RBMT scores to recent ecstasy/MDMA users who did not take other drugs 48 – 24 hours before testing, but scored significantly better than recent ecstasy/MDMA users who took various other drugs (mainly cannabis) 48 – 24 hours before testing. For both tasks the control, recent ecstasy/MDMA and abstinent ecstasy/MDMA users did not differ in their change of performance across 24 hours; there was thus no evidence that ecstasy/MDMA impairs the memory consolidation function of sleep for either declarative or procedural memory. For participants in the two ecstasy/MDMA groups greater lifetime consumption of ecstasy tablets was associated with significantly more deficits in procedural memory. Furthermore, greater lifetime consumption of ecstasy tablets and of cocaine, were also associated with significantly more deficits in declarative memory. PMID:20615932

Studies of (±)-3,4-methylenedioxymethamphetamine (MDMA) metabolism and disposition in rats and mice: relationship to neuroprotection and neurotoxicity profile.

Science.gov (United States)

Mueller, Melanie; Maldonado-Adrian, Concepcion; Yuan, Jie; McCann, Una D; Ricaurte, George A

2013-02-01

The neurotoxicity of (±)-3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to 1) assess the effect of hypothermia on MDMA metabolism, 2) determine whether the neuroprotective effect of hypothermia is related to inhibition of MDMA metabolism, and 3) determine if different neurotoxicity profiles in mice and rats are related to differences in MDMA metabolism and/or disposition in the two species. Rats and mice received single neurotoxic oral doses of MDMA at 25°C and 4°C, and body temperature, pharmacokinetic parameters, and serotonergic and dopaminergic neuronal markers were measured. Hypothermia did not alter MDMA metabolism in rats and only modestly inhibited MDMA metabolism in mice; however, it afforded complete neuroprotection in both species. Rats and mice metabolized MDMA in a similar pattern, with 3,4-methylenedioxyamphetamine being the major metabolite, followed by 4-hydroxy-3-methoxymethamphetamine and 3,4-dihydroxymethamphetamine, respectively. Differences between MDMA pharmacokinetics in rats and mice, including faster elimination in mice, did not account for the different profile of MDMA neurotoxicity in the two species. Taken together, the results of these studies indicate that inhibition of MDMA metabolism is not responsible for the neuroprotective effect of hypothermia in rodents, and that different neurotoxicity profiles in rats and mice are not readily explained by differences in MDMA metabolism or disposition.

Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

Science.gov (United States)

Bosch, Oliver G.; Wagner, Michael; Jessen, Frank; Kühn, Kai-Uwe; Joe, Alexius; Seifritz, Erich; Maier, Wolfgang; Biersack, Hans-Jürgen; Quednow, Boris B.

2013-01-01

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

Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats.

Science.gov (United States)

Schindler, Charles W; Thorndike, Eric B; Blough, Bruce E; Tella, Srihari R; Goldberg, Steven R; Baumann, Michael H

2014-01-01

The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats. MDMA (1-20 mg·kg(-1)) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10 mg·kg(-1)) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β-adrenoceptor antagonist propranolol. Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users.

Science.gov (United States)

Morefield, Kate M; Keane, Michael; Felgate, Peter; White, Jason M; Irvine, Rodney J

2011-07-01

To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

Science.gov (United States)

Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa

2015-01-01

Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress.

Directory of Open Access Journals (Sweden)

Javier Navarro-Zaragoza

Full Text Available Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA. The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27, after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA. Drinking in the dark (DID procedure was used as a model of binge. Noradrenaline (NA turnover, tyrosine hydroxylase (TH, TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN were determined by high-performance liquid chromatography (HPLC; TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.

Differential response of nNOS knockout mice to MDMA ("ecstasy")- and methamphetamine-induced psychomotor sensitization and neurotoxicity.

Science.gov (United States)

Itzhak, Yossef; Anderson, Karen L; Ali, Syed F

2004-10-01

It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) gene are resistant to cocaine-induced psychomotor sensitization and methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was undertaken to investigate the hypothesis that nNOS has a major role in dopamine (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to the psychomotor-stimulating and neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. Repeated administration of MDMA for 5 days resulted in psychomotor sensitization in both WT and nNOS KO mice, while repeated administration of METH caused psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These findings suggest that the induction of psychomotor sensitization to MDMA and METH is NO independent and NO dependent, respectively, while the persistence of sensitization to both drugs is NO dependent. For the neurochemical studies, a high dose of MDMA caused marked depletion of 5-HT in several brain regions of both WT and KO mice, suggesting that the absence of the nNOS gene did not afford protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic neurotoxicity caused by high doses of MDMA and METH in WT mice was partially prevented in KO mice administered with MDMA, but it was fully precluded in KO mice administered with METH. The differential response of nNOS KO mice to the behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is required for the expression and persistence of DA-mediated effects of METH and MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT depletion) are not dependent on nNOS.

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

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Swann Alan C

2006-01-01

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

MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its stereoisomers: Similarities and differences in behavioral effects in an automated activity apparatus in mice.

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Young, Richard; Glennon, Richard A

2008-01-01

Racemic MDMA (0.3-30 mg/kg), S(+)-MDMA (0.3-30 mg/kg), R(-)-MDMA (0.3-50 mg/kg) and saline vehicle (10 ml/kg) were comprehensively evaluated in fully automated and computer-integrated activity chambers, which were designed for mice, and provided a detailed analysis of the frequency, location, and/or duration of 18 different activities. The results indicated that MDMA and its isomers produced stimulation of motor actions, with S(+)-MDMA and (+/-)-MDMA usually being more potent than R(-)-MDMA in measures such as movement (time, distance, velocity), margin distance, rotation (clockwise and counterclockwise), and retraced activities. Interestingly, racemic MDMA appeared to exert a greater than expected potency and/or an enhanced effect on measures such as movement episodes, center actions (entries and distance), clockwise rotations, and jumps; actions that might be explained by additive or synergistic (i.e. potentiation) effects of the stereoisomers. In other measures, the enantiomers displayed different effects: S(+)-MDMA produced a preference to induce counterclockwise (versus clockwise) rotations, and each isomer exerted a different profile of effect on vertical activities and jumps. Furthermore, each isomer of MDMA appeared to attenuate the effect of its opposite enantiomer on some behaviors; antagonism effects that were surmised from a lack of expected activities by racemic MDMA. S(+)-MDMA (but not R(-)-MDMA), for example, produced an increase in vertical entries (rearing) and a preference to increase counterclockwise (versus clockwise) rotations; (+/-)-MDMA also should have induced such effects but did not. Apparently, R(-)-MDMA, when combined with S(+)-MDMA to form (+/-)-MDMA, prevented the appearance of those increases (from control) in activities. Similarly, R(-)-MDMA (but not S(+)-MDMA) produced increases in episodes (i.e. jumps) and vertical distance that racemic MDMA also should have, but were not, exhibited. Evidently, the presence of S(+)-MDMA in the

Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").

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McNamara, Ruth; Kerans, Aoife; O'Neill, Barry; Harkin, Andrew

2006-01-01

The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of

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

NARCIS (Netherlands)

Reneman, Liesbeth; Schilt, T.; de Win, Maartje M.; Booij, Jan; Schmand, Ben; van den Brink, Wim; Bakker, Onno

2006-01-01

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

MDMA (Ecstacy): Useful Information for Health Professionals Involved in Drug Education Programs.

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Elk, Carrie

1996-01-01

Provides a brief history of 3,4-ethylenedioxymethamphetamine (MDMA). Presents a summation of current findings and implications including MDMA in drug education. Examines typical dosage, effects, user profile, and therapeutic aspects. Calls for increased research to address the lack of formal scientific data regarding the nature and effects of…

Learning, Memory, and Executive Function in New MDMA Users: A Two-Year Follow-up Study

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Daniel eWagner

2015-12-01

Full Text Available 3,4-Methylenedioxymethamphetamine (MDMA is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a two-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. 96 subjects were assessed at the second follow-up assessment: 31 of these were non-users, 55 moderate-users and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns and subjective well-being were assessed.The Repeated measures analysis of variance (rANOVA revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of two years. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, in the recent study, further deterioration in continuing MDMA-users was not observed.

Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis).

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Ballesta, Sébastien; Reymond, Gilles; Pozzobon, Matthieu; Duhamel, Jean-René

2016-01-01

3,4-methylenedioxy-N-methyl amphetamine (MDMA) is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg) to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors.

Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis.

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Sébastien Ballesta

Full Text Available 3,4-methylenedioxy-N-methyl amphetamine (MDMA is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play. In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors.

MDMA induces oxytocin release in humans

NARCIS (Netherlands)

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

2008-01-01

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

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

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Cédric M Hysek

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

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

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

2015-10-01

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

Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

International Nuclear Information System (INIS)

Fonsart, Julien; Menet, Marie-Claude; Decleves, Xavier; Galons, Herve; Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel; Noble, Florence

2008-01-01

The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg -1 sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences

The high prevalence of substance use disorders among recent MDMA users compared with other drug users: implications for intervention

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Wu, Li-Tzy; Parrott, Andy C.; Ringwalt, Christopher L.; Patkar, Ashwin A.; Mannelli, Paolo; Blazer, Dan G.

2009-01-01

Aim In light of the resurgence in MDMA use and its association with polysubstance use, we investigated the 12-month prevalence of substance use disorders (SUDs) among adult MDMA users to determine whether they are at risk of other drug-related problems that would call for targeted interventions. Methods Data were drawn from the 2006 National Survey on Drug Use and Health. Past-year adult drug users were grouped into three mutually exclusive categories: 1) recent MDMA users, who had used the drug within the past year; 2) former MDMA users, who had a history of using this drug but had not done so within the past year; and 3) other drug users, who had never used MDMA. Logistic regression procedures were used to estimate the association between respondents’ SUDs and MDMA use while adjusting for their socioeconomic status, mental health, age of first use, and history of polydrug use. Results Approximately 14% of adults reported drug use in the past year, and 24% of those past-year drug users reported a history of MDMA use. Recent MDMA users exhibited the highest prevalence of disorders related to alcohol (41%), marijuana (30%), cocaine (10%), pain reliever/opioid (8%), and tranquilizer (3%) use. Adjusted logistic regression analyses revealed that, relative to other drug users, those who had recently used MDMA were twice as likely to meet criteria for marijuana and pain reliever/opioid use disorders. They were also about twice as likely as former MDMA users to meet criteria for marijuana, cocaine, and tranquilizer use disorders. Conclusions Seven out of ten recent MDMA users report experiencing an SUD in the past year. Adults who have recently used MDMA should be screened for possible SUDs to ensure early detection and treatment. PMID:19361931

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

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

2015-05-01

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

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

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Parrott, Andrew C

2013-09-01

Serotonergic neurotoxicity following MDMA is well-established in laboratory animals, and neuroimaging studies have found lower serotonin transporter (SERT) binding in abstinent Ecstasy/MDMA users. Serotonin is a modulator for many different psychobiological functions, and this review will summarize the evidence for equivalent functional deficits in recreational users. Declarative memory, prospective memory, and higher cognitive skills are often impaired. Neurocognitive deficits are associated with reduced SERT in the hippocampus, parietal cortex, and prefrontal cortex. EEG and ERP studies have shown localised reductions in brain activity during neurocognitive performance. Deficits in sleep, mood, vision, pain, psychomotor skill, tremor, neurohormonal activity, and psychiatric status, have also been demonstrated. The children of mothers who take Ecstasy/MDMA during pregnancy have developmental problems. These psychobiological deficits are wide-ranging, and occur in functions known to be modulated by serotonin. They are often related to lifetime dosage, with light users showing slight changes, and heavy users displaying more pronounced problems. In summary, abstinent Ecstasy/MDMA users can show deficits in a wide range of biobehavioral functions with a serotonergic component. Copyright © 2013 Elsevier Ltd. All rights reserved.

The identification of a chlorinated MDMA

Czech Academy of Sciences Publication Activity Database

Marešová, V.; Hampl, J.; Chundela, Z.; Zrcek, F.; Polášek, Miroslav; Chadt, J.

2005-01-01

Roč. 29, č. 5 (2005), s. 353-358 ISSN 0146-4760 Institutional research plan: CEZ:AV0Z40400503 Keywords : designer drugs ecstasy * 3,4-methylenedioxymethamphetamine MDMA * psychomot performance * clinical pharmacology Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.785, year: 2005

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy.

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Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick

2017-08-01

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.

Human psychobiology of MDMA or 'Ecstasy': an overview of 25 years of empirical research.

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Parrott, Andrew C

2013-07-01

This paper aimed to review how scientific knowledge about the human psychobiology of MDMA has developed over time. In this paper, the empirical findings from earlier and later studies will be reviewed. When MDMA was a 'novel psychoactive substance', it was not seen as a drug of abuse, as it displayed loss of efficacy. However, recreational users display a unique pattern of increasing doses, deteriorating cost-benefit ratios, and voluntary cessation. MDMA increases body temperature and thermal stress, with cortisol levels increased by 800% in dance clubbers. It can be extremely euphoric, although negative moods are also intensified. MDMA causes apoptosis (programmed cell death) and has been investigated for cancer therapy because of its anti-lymphoma properties. Recreational users show deficits in retrospective memory, prospective memory, higher cognition, problem solving, and social intelligence. Basic cognitive skills remain intact. Neuroimaging studies show reduced serotonin transporter levels across the cerebral cortex, which are associated with neurocognitive impairments. Deficits also occur in sleep architecture, sleep apnoea, complex vision, pain, neurohormones, and psychiatric status. Ecstasy/MDMA use during pregnancy leads to psychomotor impairments in the children. The damaging effects of Ecstasy/MDMA are far more widespread than was realized a few years ago, with new neuropsychobiological deficits still emerging. Copyright © 2013 John Wiley & Sons, Ltd.

MDMA ‘ecstasy’ increases cerebral cortical perfusion determined by bolus-tracking arterial spin labelling (btASL) MRI

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Rouine, J; Gobbo, O L; Campbell, M; Gigliucci, V; Ogden, I; McHugh Smith, K; Duffy, P; Behan, B; Byrne, D; Kelly, M E; Blau, C W; Kerskens, C M; Harkin, A

2013-01-01

Background and Purpose The purpose of this study was to assess cerebral perfusion changes following systemic administration of the recreational drug 3,4-methylendioxymethamphetamine (MDMA ‘ecstasy’) to rats. Experimental Approach Cerebral perfusion was quantified using bolus-tracking arterial spin labelling (btASL) MRI. Rats received MDMA (20 mg·kg−1; i.p.) and were assessed 1, 3 or 24 h later. Rats received MDMA (5 or 20 mg·kg−1; i.p.) and were assessed 3 h later. In addition, rats received MDMA (5 or 10 mg·kg−1; i.p.) or saline four times daily over 2 consecutive days and were assessed 8 weeks later. Perfusion-weighted images were generated in a 7 tesla (7T) MRI scanner and experimental data was fitted to a quantitative model of cerebral perfusion to generate mean transit time (MTT), capillary transit time (CTT) and signal amplitude. Key Results MDMA reduces MTT and CTT and increases amplitude in somatosensory and motor cortex 1 and 3 h following administration, indicative of an increase in perfusion. Prior exposure to MDMA provoked a long-term reduction in cortical 5-HT concentration, but did not produce a sustained effect on cerebral cortical perfusion. The response to acute MDMA challenge (20 mg·kg−1; i.p.) was attenuated in these animals indicating adaptation in response to prior MDMA exposure. Conclusions and Implications MDMA provokes changes in cortical perfusion, which are quantifiable by btASL MRI, a neuroimaging tool with translational potential. Future studies are directed towards elucidation of the mechanisms involved and correlating changes in cerebrovascular function with potential behavioural deficits associated with drug use. PMID:23517012

Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

Directory of Open Access Journals (Sweden)

O'Shea Esther

2011-05-01

Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

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

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Spronk, D B; Dumont, G J H; Verkes, R J; De Bruijn, E R A

2014-07-01

Knowing how commonly used drugs affect performance monitoring is of great importance, because drug use is often associated with compromised behavioral control. Two of the most commonly used recreational drugs in the western world, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and ethanol (alcohol), are also often used in combination. The error-related negativity (ERN), correct-related negativity (CRN), and N2 are electrophysiological indices of performance monitoring. The present study aimed to investigate how ethanol, MDMA, and their co-administration affect performance monitoring as indexed by the electrophysiological correlates. Behavioral and EEG data were obtained from 14 healthy volunteers during execution of a speeded choice-reaction-time task after administration of ethanol, MDMA, and combined ethanol and MDMA, in a double-blind, placebo-controlled, randomized crossover design. Ethanol significantly reduced ERN amplitudes, while administration of MDMA did not affect the ERN. Co-administration of MDMA and ethanol did not further impair nor ameliorate the effect of ethanol alone. No drug effects on CRN nor N2 were observed. A decreased ERN following ethanol administration is in line with previous work and offers further support for the impairing effects of alcohol intoxication on performance monitoring. This impairment may underlie maladaptive behavior in people who are under influence. Moreover, these data demonstrate for the first time that MDMA does not affect performance monitoring nor does it interact with ethanol in this process. These findings corroborate the notion that MDMA leaves central executive functions relatively unaffected.

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

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Nicola, Valentina G.; Vischer, Nerina; Donzelli, Massimiliano; Krähenbühl, Stephan; Grouzmann, Eric; Huwyler, Jörg; Hoener, Marius C.; Liechti, Matthias E.

2012-01-01

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence. Trial Registration Clinicaltrials.gov NCT00990067 PMID:22574166

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

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

2015-01-01

(+/−)3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is an abused psychostimulant producing strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCP), primarily a type specific to skeletal muscle (UCP-3) and which is absent in brain, although other UCP types are expressed in brain (e.g., thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights of MDMA action, we measured spatial distributions of systemically-administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation of Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA4−)). The MDMA-induced temperature rise in cortex was greater than in subcortex (1.6±0.4°C vs. 1.3±0.4°C) and occurred more rapidly (2.0±0.2°C/h vs. 1.5±0.2°C/h). MDMA-induced temperature changes and dynamics in cortex and body were correlated, although body temperature exceeded cortex before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in cortex and subcortex (i.e., thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to cortex, a biphasic relationship was seen in subcortex (i.e., thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature >37°C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as

Contribution of Impulsivity and Serotonin Receptor Neuroadaptations to the Development of an MDMA ('Ecstasy') Substance Use Disorder.

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Schenk, Susan; Aronsen, Dane

As is the case with other drugs of abuse, a proportion of ecstasy users develop symptoms consistent with a substance use disorder (SUD). In this paper, we propose that the pharmacology of MDMA, the primary psychoactive component of ecstasy tablets, changes markedly with repeated exposure and that neuroadaptations in dopamine and serotonin brain systems underlie the shift from MDMA use to MDMA misuse in susceptible subjects. Data from both the human and laboratory animal literature are synthesized to support the idea that (1) MDMA becomes a less efficacious serotonin releaser and a more efficacious dopamine releaser with the development of behaviour consistent with an SUD and (2) that upregulated serotonin receptor mechanisms contribute to the development of the MDMA SUD via dysregulated inhibitory control associated with the trait of impulsivity.

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

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Kamilar-Britt, Philip; Bedi, Gillinder

2015-01-01

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

Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat†

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Perrine, Shane A.; Michaels, Mark S.; Ghoddoussi, Farhad; Hyde, Elisabeth M.; Tancer, Manuel E.; Galloway, Matthew P.

2009-01-01

Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection...

The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice.

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Saadat, Kathryn S; Elliott, J Martin; Colado, M Isabel; Green, A Richard

2006-03-01

When mice are exposed to harmless objects such as marbles in their cage they bury them, a behaviour sometimes known as defensive burying. We investigated the effect of an acute dose of MDMA (èecstasy') and other psychoactive drugs on marble burying and also examined the effect of a prior neurotoxic dose of MDMA or p-chloroamphetamine (PCA) on burying. Acute administration of MDMA produced dose-dependent inhibition of marble burying (EC50: 7.6 micro mol/kg). Other drugs that enhance monoamine function also produced dose-dependent inhibition: methamphetamine PCA paroxetine MDMA GBR 12909 methylphenidate. None of these drugs altered locomotor activity at a dose that inhibited burying. A prior neurotoxic dose of MDMA, which decreased striatal dopamine content by 60%, but left striatal 5-HT content unaltered, did not alter spontaneous marble burying 18 or 40 days later. However, a neurotoxic dose of PCA which decreased striatal dopamine by 60% and striatal 5-HT by 70% attenuated marble burying 28 days later. Overall, these data suggest that MDMA, primarily by acutely increasing 5-HT function, acts like several anxiolytic drugs in this behavioural model. Long-term loss of cerebral 5-HT content also produced a similar effect. Since this change was observed only after 28 days, it is probably due to an adaptive response in the brain.

Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain.

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Frau, Lucia; Simola, Nicola; Porceddu, Pier Francesca; Morelli, Micaela

2016-09-01

3,4-methylenedyoxymethamphetamine (MDMA or "ecstasy"), a recreational drug of abuse, can induce glia activation and dopaminergic neurotoxicity. Since MDMA is often consumed in crowded environments featuring high temperatures, we studied how these factors influenced glia activation and dopaminergic neurotoxicity induced by MDMA. C57BL/6J adolescent (4 weeks old) and adult (12 weeks old) mice received MDMA (4×20mg/kg) in different conditions: 1) while kept 1, 5, or 10×cage at room temperature (21°C); 2) while kept 5×cage at either room (21°C) or high (27°C) temperature. After the last MDMA administration, immunohistochemistry was performed in the caudate-putamen for CD11b and GFAP, to mark microglia and astroglia, and in the substantia nigra pars compacta for tyrosine hydroxylase, to mark dopaminergic neurons. MDMA induced glia activation and dopaminergic neurotoxicity, compared with vehicle administration. Crowding (5 or 10 mice×cage) amplified MDMA-induced glia activation (in adult and adolescent mice) and dopaminergic neurotoxicity (in adolescent mice). Conversely, exposure to a high environmental temperature (27°C) potentiated MDMA-induced glia activation in adult and adolescent mice kept 5×cage, but not dopaminergic neurotoxicity. Crowding and exposure to a high environmental temperature amplified MDMA-induced hyperthermia, and a positive correlation between body temperature and activation of either microglia or astroglia was found in adult and adolescent mice. These results provide further evidence that the administration setting influences the noxious effects of MDMA in the mouse brain. However, while crowding amplifies both glia activation and dopaminergic neurotoxicity, a high environmental temperature exacerbates glia activation only. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories.

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Carhart-Harris, R L; Wall, M B; Erritzoe, D; Kaelen, M; Ferguson, B; De Meer, I; Tanner, M; Bloomfield, M; Williams, T M; Bolstridge, M; Stewart, L; Morgan, C J; Newbould, R D; Feilding, A; Curran, H V; Nutt, D J

2014-04-01

3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.

Sex differences in abuse-related neurochemical and behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats.

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Lazenka, M F; Suyama, J A; Bauer, C T; Banks, M L; Negus, S S

2017-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is a substrate for dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse-related MDMA effects, the present study compared MDMA effects on intracranial self-stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague-Dawley rats. For ICSS studies, electrodes were implanted in the medial forebrain bundle and rats trained to press for electrical stimulation over a range of frequencies (56-158Hz, 0.05 log increments) under a fixed-ratio 1 schedule, and the potency (0.32-3.2mg/kg, 10min pretreatment) and time course (3.2. mg/kg, 10-180min pretreatment) of MDMA effects were determined. For in vivo microdialysis, rats were implanted with bilateral guide cannulae targeting the NAc, and the time course of MDMA effects (1.0-3.2mg/kg, 0-180min) on DA and 5HT was determined. MDMA produced qualitatively similar effects in both sexes on ICSS (both increases in low ICSS rates maintained by low brain-stimulation frequencies and decreases in high ICSS rates maintained by high brain-stimulation frequencies) and microdialysis (increases in both DA and 5HT). The duration and peak levels of both abuse-related ICSS facilitation and increases in NAc DA were longer in females. MDMA was also more potent to increase 5HT in females. These results provide evidence for heightened sensitivity of females to abuse-related behavioral and neurochemical effects of MDMA in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its Stereoisomers: Similarities and Differences in Behavioral Effects in an Automated Activity Apparatus in Mice

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Young, Richard; Glennon, Richard A.

2007-01-01

Racemic MDMA (0.3 – 30 mg/kg), S(+)-MDMA (0.3 – 30 mg/kg), R(-)-MDMA (0.3 – 50 mg/kg) and saline vehicle (10 ml/kg) were comprehensively evaluated in fully automated and computer-integrated activity chambers, which were designed for mice, and provided a detailed analysis of the frequency, location, and/or duration of 18 different activities. The results indicated that MDMA and its isomers produced stimulation of motor actions, with S(+)-MDMA and (±)-MDMA usually being more potent than R(-)-MD...

Acute behavioral effects of co-administration of mephedrone and MDMA in mice.

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Budzynska, Barbara; Michalak, Agnieszka; Frankowska, Małgorzata; Kaszubska, Katarzyna; Biała, Grażyna

2017-04-01

Abuse of more than one psychoactive drug is becoming a global problem. Our experiments were designed to examine the effects of a concomitant administration of 3,4-methylenedioxy-methamphetamine (MDMA) and mephedrone on depression- and anxiety-like behaviors and cognitive processes in Swiss mice. In order to investigate the drug interactions the forced swimming test (FST) - an animal model of depression, the passive avoidance (PA) test - a memory and learning paradigm, as well as the elevated plus maze (EPM) test - test for anxiety level were used. The results revealed that a concomitant administration of non-effective doses of mephedrone (1mg/kg) and MDMA (1mg/kg) exerted marked antidepressive effects in the FST. Also a co-administration of mephedrone (2.5mg/kg) and MDMA (1mg/kg) displayed a pro-cognitive action in the PA paradigm. Furthermore, even though mephedrone and MDMA can, in general, exert some anxiogenic effects in mice, the concomitant administration of nonactive doses of both drugs (0.05 and 0.1mg/kg, respectively) in the EPM test, did not show any synergistic effect in our study. The effects of mephedrone and MDMA combination on mammalian organisms were attempted to be evaluated in our study and the results are described in the present report. These results may help explain the reasons for and consequences of a concomitant administration of psychoactive substances with regards to the central nervous system, while being possibly useful in the treatment of polydrug intoxication. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Ghrelin Alleviates MDMA-Induced Disturbance of Serum Glucose and Lipids Levels in the Rat

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Ravieh Golchoobian

2018-01-01

Full Text Available Hepatotoxicity is one of the clinically adverse effects of ecstasy (3, 4-methylenedioxymethamphetamine; MDMA consumption. The detoxification tissue, liver, plays a central role in maintaining circulating levels of glucose and lipid. Hypoglycemia and hypotriglyceridemia have been reported due to ecstasy abuse. Ghrelin is a 28-amino-acid peptide secreted predominantly from the stomach. It has been demonstrated that ghrelin has hepatoprotective effects and is able to increase blood glucose concentration. In the current study, we explored the effect of hepatotoxic dose of MDMA and therapeutic use of exogenous ghrelin on the serum levels of glucose and lipids in four groups of rats. MDMA caused a severe and transient reduction in circulating levels of glucose and triglyceride and increased serum LDL. However, cholesterol and HDL levels remained unchanged. Meanwhile, altered hepatic architecture was observed with intracellular vacuolation that may indicate intracellular accumulation of lipid droplets. In addition, following ghrelin administration, the blood sugar levels improved and LDL levels returned to the baseline value, and ghrelin treatment did not improve triglycerides levels. These results showed that MDMA causes hypoglycemia, hypotriglyceridemia, and hyper LDL-cholesterolemia. To our knowledge, this is the first report showing ghrelin administration could improve hypoglycemia and normalize LDL levels induced by MDMA and partially restore hepatic architecture.

The most frequent psychopathology related to the use of 3,4-methylenedioxymethamphetamine (MDMA of medical help seekers: causality or coincidence?

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Mercedes Lovrečič

2011-11-01

Full Text Available Background: 3,4-methylendioxymethamphetamine (MDMA represents the most popular recreational synthetic drug. The increasing popularity of MDMA, health consequences due to its recreational use and possibility of neurodegeneration of brain serotonin neurons are the reasons for increasing concern. Numerous studies suggest a link between exposure to MDMA and the consequent psychopathology. The literature indicates the incidence of various psychiatric disorders associated with single or multiple use of MDMA. The most frequent psychiatric disorders for which MDMA users search medical assistance are psychotic states, depression and panic attacks. However, it is not easy to conclude that there is a causal link between exposure to MDMA and psychopathology. This paper describes current knowledge of some aspects of this phenomenon, which represents the starting point for further challenges to various researchers and experts.

Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

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Fonsart, Julien; Menet, Marie-Claude; Debray, Marcel; Hirt, Deborah; Noble, Florence; Scherrmann, Jean-Michel; Decleves, Xavier

2009-01-01

The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC last and C max were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C max and AUC last were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC last and t 1/2 were 50% higher in females given MDMA (1 mg/kg iv). MDA C max and AUC last were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC last of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model.

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Jamshidfar, Sanaz; Ardakani, Yalda H; Lavasani, Hoda; Rouini, Mohammadreza

2017-06-28

Nowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound. Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression. MRZ is extensively metabolized in liver by CYP450 isoenzymes. 8-hydroxymirtazapine (8-OH) is mainly produced by CYP2D6. N-desmethylmirtazapine (NDES) is generated by CYP3A4. MDMA is also metabolized by the mentioned isoenzymes and demonstrates mechanism-based inhibition (MBI) in association with CYP2D6. Several studies revealed that MDMA showed inhibitory effects on CYP3A4. In the present study, our aim was to evaluate the impact of MDMA on the metabolism of MRZ in liver. Therefore, isolated perfused rat liver model was applied as our model of choice in this assessment. The subjects of the study were categorized into two experimental groups. Rats in the control group received MRZ-containing Krebs-Henselit buffer (1 μg/ml). Rats in the treatment group received aqueous solution of 1 mg/ml MDMA (3 mg/kg) intraperitoneally 1 hour before receiving MRZ. Perfusate samples were analyzed by HPLC. Analyses of perfusate samples showed 80% increase in the parent drug concentrations and 50% decrease in the concentrations of both metabolites in our treatment group compared to the control group. In the treatment group compared to the control group, AUC (0-120) of the parent drug demonstrated 50% increase and AUC (0-120) of 8-OH and NDES showed 70% and 60% decrease, respectively. Observed decrease in metabolic ratios were 83% and 79% for 8-OH and NDES in treatment group compared to control group, respectively. Hepatic clearance (CL h ) and intrinsic clearance (Cl int ) showed 20% and 60% decrease in treatment group compared to control group. All findings prove the inhibitory effects of ecstasy on both CYP2D6 and CYP3A4 hepatic isoenzymes. In

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

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

2015-01-01

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

Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence.

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Cadoni, Cristina; Pisanu, Augusta; Simola, Nicola; Frau, Lucia; Porceddu, Pier Francesca; Corongiu, Silvia; Dessì, Christian; Sil, Annesha; Plumitallo, Antonio; Wardas, Jadwiga; Di Chiara, Gaetano

2017-09-01

Although MDMA (3,4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine (Energy Drinks) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-à-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats. MDMA reduced density of tyrosine hydroxylase (TH) positive neurons in the ventral tegmental area and in the substantia nigra pars compacta, and immunoreactivity of TH and DA transporter in the nucleus accumbens (NAc) shell and core, and caudate-putamen. This same treatment caused a reduction of basal dialysate DA in the NAc core. MDMA-pretreated rats also showed behavioral sensitization to a MDMA challenge at adulthood and potentiation of MDMA-induced increase of dialysate DA in the NAc core, but not in the NAc shell. In addition, MDMA-treated rats displayed a deficit in recognition memory. Caffeine co-administration did not affect the above outcomes. Our results show that adolescent exposure of rats to low doses of MDMA induces long-lasting and widespread reduction of DA neurons indicative of a neurotoxic effect on DA neurons and suggestive of a degeneration of the same neurons. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy.

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Amoroso, Timothy; Workman, Michael

2016-07-01

Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD. © The Author(s) 2016.

Why MDMA therapy for alcohol use disorder? And why now?

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Sessa, Ben

2017-11-07

Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were associated with Lysergic acid diethylamide (LSD)-assisted psychotherapy to treat what was then called, alcoholism. But results were varied and psychedelic therapy with LSD and other 'classical' psychedelics fell out of favour in the wake of socio-political pressures and cultural changes. A current revisiting of psychedelic clinical research is now targeting substance use disorders - and particularly alcohol use disorder - again. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has never been formally explored as a treatment for any form of substance use disorder. But in recent years MDMA has risen in prominence as an agent to treat posttraumatic stress disorder (PTSD). With its unique receptor profile and a relatively well-tolerated subjective experience of drug effects when used clinically, MDMA Therapy is ideally suited to allow a patient to explore and address painful memories without being overwhelmed by negative affect. Given that alcohol use disorder is so often associated with early traumatic experiences, the author is proposing in a current on-going UK-based study that patients with alcohol use disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neurochemical and neuroanatomic effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats

International Nuclear Information System (INIS)

Virus, R.; Commins, D.; Vosmer, G.; Woolverton, W.; Schuster, C.; Seiden, L.

1986-01-01

Rats injected s.c. twice daily for 4 consecutive days with 10,20, or 40 mg/kg MDMA or saline and sacrificed 2 weeks after the last injection showed dose-dependent reductions in serotonin (5-HT) concentrations in hypothalamus, hippocampus (HIP), striatum (STR), somatosensory cortex (SC) and other cortical areas (CTX). 5-HT depletion was maximal in HIP (11.5 +/- 1.7%) and SC (15.3 +/- 3.2%, p 3 H)5-HT uptake sites (V/sub max/ 35.2% of control) without affecting the affinity (K/sub m/) in HIP. Fink-Heimer staining showed that rats injected s.c. twice daily for 2 days with 80 mg/kg MDMA had greater degeneration of nerve terminals in STR (p<0.005) and pyramidal cells in Layer III of SC (p<0.01) than did control rats. These results clearly suggest that repeated exposure to MDMA selectively damages serotonergic neurons in the central nervous system of rats

Psychiatric disorders and their correlates among young adult MDMA users in Ohio.

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Falck, Russel S; Carlson, Robert G; Wang, Jichuan; Siegal, Harvey A

2006-03-01

This study describes the lifetime prevalence, correlates, and age of onset of selected psychiatric disorders among a community sample of MDMA users (n = 402), aged 18 to 30, in Ohio. Participants responded to interviewer-administered questionnaires, including sections of the computerized Diagnostic Interview Schedule for DSM-IV. Fifty-five percent of the sample had at least one lifetime disorder, with major depression (35.3%) and antisocial personality disorder (ASPD) (25.4%) the most common. Proportionately more women were diagnosed with depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD), while proportionately more men were diagnosed with ASPD. Proportionately more non-White participants had attention deficit/hyperactivity disorder (AD/HD). Higher levels of education were associated with proportionately less PTSD, ASPD, and AD/HD. Higher frequencies of MDMA use were associated with proportionately more ASPD and AD/HD. Comparing the age of first MDMA use with the age of onset for selected psychiatric disorders revealed that for most participants disorders preceded use. Multivariate analysis revealed participants with more than a high school education were less likely to have experienced a lifetime disorder, while those who had used MDMA more than 50 times were more likely. Variations in the prevalence of psychiatric disorders have practical implications for drug abuse prevention and treatment programs.

MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

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Huff, Courtney L.; Morano, Rachel L.; Herman, James P.; Yamamoto, Bryan K.; Gudelsky, Gary A.

2016-01-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. PMID:27773601

MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

Science.gov (United States)

Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

2016-12-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

Warning against co-administration of 3,4-methylenedioxymethamphetamine (MDMA) with methamphetamine from the perspective of pharmacokinetic and pharmacodynamic evaluations in rat brain.

Science.gov (United States)

Yuki, Fuchigami; Rie, Ikeda; Miki, Kuzushima; Mitsuhiro, Wada; Naotaka, Kuroda; Kenichiro, Nakashima

2013-04-11

3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine often cause serious adverse effects (e.g., rhabdomyolysis, and cardiac disease) following hyperthermia triggered by release of brain monoamines such as dopamine and serotonin. Therefore, evaluation of brain monoamine concentrations is useful to predict these drugs' risks in human. This study aimed to evaluate risks of co-administration of MDMA and methamphetamine, both of which are abused frequently in Japan, based on drug distribution and monoamine level in the rat brain. Rats were allocated to three groups: (1) sole MDMA administration (12 or 25 mg/kg, intraperitoneally), (2) sole methamphetamine administration (10 mg/kg, intraperitoneally) and (3) co-administration of MDMA (12 mg/kg, intraperitoneally) and methamphetamine (10 mg/kg, intraperitoneally). We monitored pharmacokinetic and pharmacodynamic variables for drugs and monoamines in the rat brain. Area under the curve for concentration vs. time until 600 min from drug administration (AUC₀₋₆₀₀) increased from 348.0 to 689.8 μgmin/L for MDMA and from 29.9 to 243.4 μMmin for dopamine in response to co-administration of methamphetamine and MDMA compared to sole MDMA (12 mg/kg) administration. After sole methamphetamine or that with MDMA administration, AUC₀₋₆₀₀ of methamphetamine were 401.8 and 671.1 μgmin/L, and AUC₀₋₆₀₀ of dopamine were 159.9 and 243.4 μMmin. In conclusion, the brain had greater exposure to MDMA, methamphetamine and dopamine after co-administration of MDMA and methamphetamine than when these two drugs were given alone. This suggests co-administration of MDMA with methamphetamine confers greater risk than sole administration, and that adverse events of MDMA ingestion may increase when methamphetamine is co-administered. Copyright © 2013 Elsevier B.V. All rights reserved.

MDMA and heightened cortisol: a neurohormonal perspective on the pregnancy outcomes of mothers used 'Ecstasy' during pregnancy.

Science.gov (United States)

Parrott, Andrew C; Moore, Derek G; Turner, John J D; Goodwin, Julia; Min, Meeyoung O; Singer, Lynn T

2014-01-01

The illicit recreational drug 3,4-methylenedioxymethamphetamine (MDMA) or Ecstasy has strong neurohormonal effects. When taken by recreational users at dance clubs and raves, it can generate an 800% increase in the stress hormone cortisol, whereas drug-free users show chronically raised levels of cortisol. The aim here is to critically debate this neurohormonal influence for the children of pregnant MDMA-using mothers. High levels of cortisol are known to be damaging for neuropsychobiological well-being in adult humans. MDMA can damage foetal development in laboratory animals, and the prospective Drugs and Infancy Study was established to monitor the effects of MDMA taken recreationally by pregnant women. The Drugs and Infancy Study revealed that young mothers, who took MDMA during the first trimester of pregnancy, gave birth to babies with significant gross psychomotor retardation. These mothers would have experienced high levels of cortisol due to Ecstasy/MDMA use, and since cortisol can cross the placenta, this is likely to have also occurred in the foetus. In terms of causation, the developmental problems may reflect a combination of neurotransmitter and neurohormonal effects on the hypothalamic-pituitary-adrenal axis, with serotonergic activity being influenced by the high levels of cortisol. Copyright © 2014 John Wiley & Sons, Ltd.

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

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V. Ferraz-de-Paula

2011-05-01

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

MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.

Science.gov (United States)

Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K

2015-08-15

MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

NARCIS (Netherlands)

Reneman, L.; Booij, J.; de Bruin, K.; Reitsma, J. B.; de Wolff, F. A.; Gunning, W. B.; den Heeten, G. J.; van den Brink, W.

2001-01-01

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA

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

NARCIS (Netherlands)

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

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

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

NARCIS (Netherlands)

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

2003-01-01

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

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

Directory of Open Access Journals (Sweden)

Silvio Fernandes Lapachinske

2004-03-01

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

3,4-Methylenedioxymethamphetamine (MDMA) alters acute gammaherpesvirus burden and limits Interleukin 27 responses in a mouse model of viral infection

Science.gov (United States)

Nelson, Daniel A.; Singh, Sam J.; Young, Amy B.; Tolbert, Melanie D.; Bost, Kenneth L.

2011-01-01

Aims To test whether 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) abuse might increase the susceptibility, or alter the immune response, to murine gammaherpesvirus 68 (HV-68) and/or bacterial lipopolysaccharide. Methods Groups of experimental and control mice were subjected to three day binges of MDMA, and the effect of this drug abuse on acute and latent HV-68 viral burden were assessed. In vitro and in vivo studies were also performed to assess the MDMA effect on IL-27 expression in virally infected or LPS-exposed macrophages and dendritic cells, and latently infected animals, exposed to this drug of abuse. Results Acute viral burden was significantly increased in MDMA-treated mice when compared to controls. However the latent viral burden, and physiological and behavioral responses were not altered in infected mice despite repeated bingeing with MDMA. MDMA could limit the IL-27 response of HV-68 infected or LPS-exposed macrophages and dendritic cells in vitro and in vivo, demonstrating the ability of this drug to alter normal cytokine responses in the context of a viral infection and/or a TLR4 agonist. Conclusion MDMA bingeing could alter the host’s immune response resulting in greater acute viral replication and reductions in the production of the cytokine, IL-27 during immune responses. PMID:21269783

Psychiatric profiles of mothers who take Ecstasy/MDMA during pregnancy: reduced depression 1 year after giving birth and quitting Ecstasy.

Science.gov (United States)

Turner, John J D; Parrott, Andrew C; Goodwin, Julia; Moore, Derek G; Fulton, Sarah; Min, Meeyoung O; Singer, Lynn T

2014-01-01

The recreational drug MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is associated with heightened psychiatric distress and feelings of depression. The Drugs and Infancy Study (DAISY) monitored the psychiatric symptom profiles of mothers who used Ecstasy/MDMA while pregnant, and followed them over the first year post-partum. We compared 28 young women whom took MDMA during their pregnancy with a polydrug control group of 68 women who took other psychoactive drugs while pregnant. The Brief Symptom Inventory (BSI) was completed for several periods: The first trimester of pregnancy; and 1, 4 and 12 months after childbirth. Recreational drug use was monitored at each time point. During the first trimester of pregnancy, MDMA-using mothers reported higher depression scores than the polydrug controls. At 1 year after childbirth, their BSI depression scores were significantly lower, now closer to the control group values. At the same time point, their self-reported use of MDMA became nearly zero, in contrast to their continued use of Cannabis/marijuana, nicotine and alcohol. We found significant symptom reductions in those with BSI obsessive-compulsive and interpersonal sensitivity, following Ecstasy/MDMA cessation. The findings from this unique prospective study of young recreational drug-using mothers are consistent with previous reports of improved psychiatric health after quitting MDMA.

Greater sexual risk-taking in female and male recreational MDMA/ecstasy users compared with alcohol drinkers: a questionnaire study.

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May, Aimee L; Parrott, Andrew C

2015-07-01

Previous studies have shown increased sexual risk-taking in experienced MDMA/ecstasy users. The main objectives of this study were to compare levels of sexual risk-taking between a young student sample of predominantly heterosexual MDMA users and alcohol-drinker controls and investigate potential gender differences. Recreational drug use and sexual risk questionnaires were completed by 20 MDMA users (10 females, 10 males) and 20 non-user controls (10 females, 10 males). They were predominantly university students, aged between 20-22 years, mainly heterosexual (n = 37), with three bisexual participants. MDMA users displayed significantly greater levels of sexual risk-taking than the alcohol-drinker controls. It involved significantly higher rates of casual sex, non-condom use during sex, and penetrative sexual risks. This increase in sexual riskiness occurred to a similar extent in males and females. These findings indicate that both female and male ecstasy/MDMA users reported more risky sexual behaviours, than the non-user controls. Further research into the sexual behaviour and sexual risk-taking of heterosexual MDMA users should be conducted because much of the past literature has focused on homosexual participants. Copyright © 2015 John Wiley & Sons, Ltd.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines

Science.gov (United States)

Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

2009-01-01

Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies. PMID:19877498

Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions

NARCIS (Netherlands)

Rietjens, S.J.; Hondebrink, L.; Westerink, R.H.S.; Meulenbelt, J.

2012-01-01

Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates

Hippocampal nicotinic receptors have a modulatory role for ethanol and MDMA interaction in memory retrieval.

Science.gov (United States)

Rostami, Maryam; Rezayof, Ameneh; Alijanpour, Sakineh; Sharifi, Khadijeh Alsadat

2017-08-15

The aim of the current study was to examine the effect of dorsal hippocampal nicotinic acetylcholine receptors (nAChRs) activation on the functional interaction between ethanol and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) in memory retrieval. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and memory retrieval was measured in a step-down type passive avoidance apparatus. Post-training or pre-test systemic administration of ethanol (1g/kg, i.p.) induced amnesia. Pre-test administration of ethanol reversed pre-training ethanol-induced amnesia, suggesting ethanol state-dependent learning. Pre-test intra-CA1 microinjection of different doses of MDMA (0.25-1µg/mouse) with an ineffective dose of ethanol (0.25g/kg, i.p.) also induced amnesia. Interestingly, pre-test intra-CA1 microinjection of MDMA (0.25-1µg/mouse) potentiated ethanol state-dependent learning. On the other hand, the activation of the dorsal hippocampal nAChRs by pre-test microinjection of nicotine (0.1-1µg/mouse, intra-CA1) improved amnesia induced by the co-administration of MDMD and ethanol. It is important to note that intra-CA1 microinjection of the same doses of MDMA or nicotine could not affect memory formation by itself. Pre-test intra-CA1 microinjection of nicotine (0.3-0.9µg/mouse) could not reverse amnesia induced by pre-training administration of ethanol while this treatment enhanced MDMA response on ethanol state-dependent learning. Thus, it can be concluded that there may be functional interactions among ethanol, MDMA and nicotine via the dorsal hippocampal nicotinic acetylcholine receptor mechanism in memory retrieval and drug state-dependent learning. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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Caroline Addison Carvalho Xavier

2008-01-01

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

Effects of adenosine A2a receptor agonist and antagonist on cerebellar nuclear factor-kB expression preceded by MDMA toxicity.

Science.gov (United States)

Kermanian, Fatemeh; Soleimani, Mansoureh; Pourheydar, Bagher; Samzadeh-Kermani, Alireza; Mohammadzadeh, Farzaneh; Mehdizadeh, Mehdi

2014-01-01

Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliated emotional response. MDMA is a potent monoaminergic neurotoxin with the potential of damage to brain neurons. The NF-kB family of proteins are ubiquitously expressed and are inducible transcription factors that regulate the expression of genes involved in disparate processes such as immunity and ingrowth, development and cell-death regulation. In this study we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Sixty three male Sprague-Dawley rats were injected to MDMA (10 and 20mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03mg/kg) injection. The cerebellum were then removed forcresylviolet staining, western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results showed that MDMA increased the number of cerebellar dark neurons. We observed that administration of CGS following MDMA, significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. These results indicated that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.

Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

Directory of Open Access Journals (Sweden)

Miñarro José

2010-03-01

Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

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

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

2012-12-01

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

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

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

2014-08-01

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

Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice.

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Kuteykin-Teplyakov, Konstantin; Maldonado, Rafael

2014-11-01

Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3,4-methylenedioxyamphetamine (MDMA, "Ecstasy") at low dose (3mg/kg) has differential effects on mouse social behavior. In some animals, MDMA promotes sociability without hyperlocomotion, whereas in other mice it elevates locomotor activity without affecting sociability. Both WAY-100635, a selective antagonist of 5-HT1A receptor, and L-368899, a selective oxytocin receptor antagonist, abolish prosocial effects of MDMA. Differential quantitative analysis of brain proteome by isobaric tag for relative and absolute quantification technology (iTRAQ) revealed 21 specific proteins that were highly correlated with sociability, and allowed to distinguish between entactogenic prosocial and hyperlocomotor effects of MDMA on proteome level. Our data suggest particular relevance of neurotransmission mediated by GABA B receptor, as well as proteins involved in energy maintenance for MDMA-induced sociability. Functional association network for differentially expressed proteins in cerebral cortex, hippocampus and amygdala were identified. These results provide new information for understanding the neurobiological substrate of sociability and may help to discover new therapeutic approaches to modulate social behavior in patients suffering from social fear and low sociability. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4-Methylenedioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction.

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Darracq, Michael A; Thornton, Stephen L; Minns, Alicia B; Gerona, Roy R

2016-01-01

We present a case of "ecstasy" ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites. A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking "ecstasy" at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels. This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

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Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

2014-01-01

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

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

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Cumming, Paul; Møller, Mette; Benda, Kjeld

2007-01-01

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

Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers.

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García-Cabrerizo, Rubén; García-Fuster, M Julia

2015-07-01

While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

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García-Pardo, M P; Blanco-Gandía, M C; Valiente-Lluch, M; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

2015-12-03

Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

2015-11-01

Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. Copyright © 2015 Elsevier B.V. All rights reserved.

Serotonin syndrome, disseminated intravascular coagulation, and hepatitis after a single ingestion of MDMA in an Asian woman.

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Nadkarni, Girish N; Hoskote, Sumedh S; Piotrkowski, Jared; Annapureddy, Narender

2014-01-01

N-Methyl-3,4-methylenedioxyamphetamine (MDMA), also called "Ecstasy," is a commonly abused psychoactive drug among the American youth. We present the case of a 23-year-old Korean-American woman who presented with seizure, delirium, and rigidity after MDMA ingestion. She was febrile (38.7°C), tachycardic (188 beats/min), tachypneic (26 breaths/min) with a borderline blood pressure (95/43 mm Hg). Examination revealed generalized muscle rigidity, tremors, hyperreflexia, and ocular clonus, leading to the diagnosis of serotonin syndrome. Urine toxicology screen was only positive for amphetamines, consistent with the history of MDMA ingestion. Initial laboratory testing showed thrombocytopenia, further testing showed deranged prothrombin time, partial thromboplastin time, decreased fibrinogen, and elevated D-dimer, suggesting disseminated intravascular coagulation. Hepatic transaminases trended up dramatically reflecting acute hepatitis. The patient received supportive care and improved by hospital day 3. MDMA toxicity manifested as serotonin syndrome, hepatitis, and coagulopathy is exceedingly rare. MDMA is metabolized by the hepatic CYP2D6 enzyme. Certain populations, such as Koreans, Chinese, and Japanese have a high prevalence of a polymorphism that confers reduced enzyme activity. We discuss this hypothesis as a possible cause for this severe presentation in our patient after a single ingestion.

Chiral separation of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling and its effects on oxidative stress status in rat liver.

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Lourenço, Tiago C; Bósio, Graziela C; Cassiano, Neila M; Cass, Quezia B; Moreau, Regina L M

2013-01-25

This work reports the multimiligram separation of 3,4-methylenedioxy-methamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling. The effect of both enantiomers compared to the racemic mixture was examined on the oxidative stress status of rat liver. The enantiomeric purification was performed using a based cyclodextrin chiral selector and methanol:ammonium acetate buffer (pH 6.0, 100mM) (30:70, v/v) as mobile phase. The average mass rate obtained was 40.0mg/day, providing 45.0mg of the (R)-(-)-MDMA (e.r. 99.0%) and 75.0mg (e.r. 96.0%) of (S)-(+)-MDMA. Racemic MDMA and both enantiomers were administered per orally to Wistar rats and oxidative stress status parameters, as liver total glutathione levels and malondialdehyde (MDA) production in liver were evaluated. There was a significant decrease in hepatic glutathione content in the racemic MDMA and the (R)-(-)-MDMA-treated rats when compared to the control and to (S)-(+)-MDMA. These results demonstrate that the R-enantiomer is the enantiomer that contributes to the depletion of hepatic glutathione induced by the racemic mixture. The high reactivity of the R-enantiomer of MDMA in the liver can also be observed in animals treated with (R)-(-)-MDMA. The production of malondialdehyde (MDA) by (R)-(-)-MDMA was significantly higher when compared to the other treated groups and control. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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Gramsbergen, Jan Bert; Cumming, Paul

2007-01-01

 The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose...... was monitored by telemetry. A single dose of MDMA (2-10-20 mg/kg i.v.) evoked a transient increase of interstitial glucose concentrations in striatum (139-223%) with rapid onset and of less than 2h duration, a concomitant but more prolonged lactate increase (>187%) at the highest MDMA dose and no significant...... depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1...

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

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

2011-01-01

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

Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

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

2013-01-01

Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs. PMID:24223797

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

Directory of Open Access Journals (Sweden)

Alvaro Llorente-Berzal

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

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

NARCIS (Netherlands)

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

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

The effect of the substituted amphetamines, 2.4-methylenedioxymethamphetamine (MDMA) and P-methoxyamphetamine (PMA), on platelet aggregation

International Nuclear Information System (INIS)

Sluggett, A.J.; Irvine, R.J.; Bochner, F.; Rodgers, S.; Lloyd, J.V.

2001-01-01

Full text: Illicit substituted amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA) and p-methoxyamphetamine (PMA) can cause severe toxicity. Disruption of normal coagulation mechanisms have been observed in most fatal cases. However, the precise mechanisms underlying these events are not clearly understood. MDMA and PMA are known to inhibit serotonin transporter function in the central nervous system (Daws et al 2000) and platelet serotonin transporter sites (Rudnick and Wall 1992). Serotonin is in high concentrations in platelets and activation of 5HT 2 receptors on the platelet surface potentiates aggregation of platelets. Therefore, we postulated that MDMA and PMA may have effects on coagulation via inhibition of normal platelet function. Human citrated platelets were incubated in the presence of MDMA (43- 435μM) or PMA (49-498μM) and their aggregator y response to a critical dose of adenosine diphosphate (ADP) determined. These responses were compared to the serotonin reuptake inhibitor fluoxetine (13-130μM). All 3 compounds were found to inhibit platelet aggregation. The IC50s for % aggregation at 5 minutes were MDMA 197μM ± 63μM PMA 344μM ±76μM and fluoxetine 24μM ±1 1μM (n=4). The effect of these drugs on the uptake of 14 C-5HT (0.9 μM /ml) into platelets was also determined and the IC50s observed were MDMA 62.3 μM ±11μM , PMA 24μM ±6μM and fluoxetine 2.5μM ± 0.6μM (n=4). The in vitro effects of MDMA and PMA on aggregation and uptake observed here are close to concentrations reported to have occurred in human fatalities. Therefore it is possible that direct effects of these drugs on coagulation mechanisms may contribute to the toxicity of these compounds. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

MDMA ('Ecstasy'), oxytocin and vasopressin modulate social preference in rats: A role for handling and oxytocin receptors.

Science.gov (United States)

Ramos, Linnet; Hicks, Callum; Caminer, Alex; Couto, Kalliu; Narlawar, Rajeshwar; Kassiou, Michael; McGregor, Iain S

In laboratory rats, peripheral administration of the neuropeptides oxytocin (OT) and vasopressin (AVP) induces similar prosocial effects (i.e. increased adjacent lying) to the party drug 3,4-methylenedioxymethamphetamine (MDMA), which are sensitive to vasopressin V 1A receptor (V 1A R) antagonism. Here, we employed a social preference paradigm to further compare the prosocial effects of OT, AVP and MDMA. We also investigated the possible involvement of the V 1A R and oxytocin receptor (OTR) in rodent social preference. The social preference paradigm measures investigation times towards an empty wire cage (presented for 4min) followed by an identical cage containing a novel rat (also presented for 4min). Social preference is defined as greater investigation time towards the inhabited cage than the empty cage. Results indicated that well-handled rats exhibited no social preference at baseline, while intraperitoneally injected MDMA (5mg/kg), OT (0.5mg/kg) and AVP (0.005mg/kg) increased social preference. However, this effect was primarily due to reduced investigation of the empty cage. In contrast, rats that received minimal prior handling displayed a social preference at baseline, while MDMA (5mg/kg), OT (0.5mg/kg) and AVP (0.005mg/kg) reduced investigation times towards both the empty and inhabited cages. Lower doses of MDMA, OT and AVP were ineffective. The OTR antagonist Compound 25 (C25, 5mg/kg), but not the V 1A R antagonist SR49059 (1mg/kg), reduced the baseline social preference seen in minimally-handled rats and prevented the social preference induced by OT and AVP (but not MDMA) in well-handled rats. Overall, these results further confirm prosocial actions of MDMA, OT and AVP, which are dependent on handling history. These findings also indicate that social preference is sensitive to OTR rather than V 1A R modulation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

2011-01-01

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

A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

Science.gov (United States)

Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

2014-12-01

Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA.

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

2016-05-01

4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5-HT(1B) agonists.

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Aronsen, Dane; Schenk, Susan

2016-04-01

Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT(1A) and 5-HT(1B) receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA. This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT(1A) agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), and the 5-HT(1B/1A) agonist, RU 24969. Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20-58 daily self-administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03-1.0 mg/kg) or the adipsic response to RU 24969 (0.3-3.0 mg/kg) were assessed. 8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self-administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration. Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms.

The role of adenosine A1 and A2A receptors in the caffeine effect on MDMA-induced DA and 5-HT release in the mouse striatum.

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Górska, A M; Gołembiowska, K

2015-04-01

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") popular as a designer drug is often used with caffeine to gain a stronger stimulant effect. MDMA induces 5-HT and DA release by interaction with monoamine transporters. Co-administration of caffeine and MDMA may aggravate MDMA-induced toxic effects on DA and 5-HT terminals. In the present study, we determined whether caffeine influences DA and 5-HT release induced by MDMA. We also tried to find out if adenosine A1 and A2A receptors play a role in the effect of caffeine by investigating the effect of the selective adenosine A1 and A2A receptor antagonists, DPCPX and KW 6002 on DA and 5-HT release induced by MDMA. Mice were treated with caffeine (10 mg/kg) and MDMA (20 or 40 mg/kg) alone or in combination. DA and 5-HT release in the mouse striatum was measured using in vivo microdialysis. Caffeine exacerbated the effect of MDMA on DA and 5-HT release. DPCPX or KW 6002 co-administered with MDMA had similar influence as caffeine, but KW 6002 was more potent than caffeine or DPCPX. To exclude the contribution of MAO inhibition by caffeine in the caffeine effect on MDMA-induced increase in DA and 5-HT, we also tested the effect of the nonxanthine adenosine receptor antagonist CGS 15943A lacking properties of MAO activity modification. Our findings indicate that adenosine A1 and A2A receptor blockade may account for the caffeine-induced exacerbation of the MDMA effect on DA and 5-HT release and may aggravate MDMA toxicity.

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

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Sessa, Ben

2017-05-10

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

Who is 'Molly'? MDMA adulterants by product name and the impact of harm-reduction services at raves.

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Saleemi, Sarah; Pennybaker, Steven J; Wooldridge, Missi; Johnson, Matthew W

2017-08-01

Methylenedioxymethamphetamine (MDMA), often sold as 'Ecstasy' or 'Molly', is commonly used at music festivals and reported to be responsible for an increase in deaths over the last decade. Ecstasy is often adulterated and contains compounds that increase morbidity and mortality. While users and clinicians commonly assume that products sold as Molly are less-adulterated MDMA products, this has not been tested. Additionally, while pill-testing services are sometimes available at raves, the assumption that these services decrease risky drug use has not been studied. This study analyzed data collected by the pill-testing organization, DanceSafe, from events across the United States from 2010 to 2015. Colorimetric reagent assays identified MDMA in only 60% of the 529 samples collected. No significant difference in the percentage of samples testing positive for MDMA was determined between Ecstasy and Molly. Individuals were significantly less likely to report intent to use a product if testing did not identify MDMA (relative risk (RR) = 0.56, p = 0.01). Results suggest that Molly is not a less-adulterated substance, and that pill-testing services are a legitimate harm-reduction service that decreases intent to consume potentially dangerous substances and may warrant consideration by legislators for legal protection. Future research should further examine the direct effects of pill-testing services and include more extensive pill-testing methods.

A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD).

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Oehen, Peter; Traber, Rafael; Widmer, Verena; Schnyder, Ulrich

2013-01-01

Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).

Human ecstasy (MDMA) polydrug users have altered brain activation during semantic processing.

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Watkins, Tristan J; Raj, Vidya; Lee, Junghee; Dietrich, Mary S; Cao, Aize; Blackford, Jennifer U; Salomon, Ronald M; Park, Sohee; Benningfield, Margaret M; Di Iorio, Christina R; Cowan, Ronald L

2013-05-01

Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) polydrug users have verbal memory performance that is statistically significantly lower than that of control subjects. Studies have correlated long-term MDMA use with altered brain activation in regions that play a role in verbal memory. The aim of our study was to examine the association of lifetime ecstasy use with semantic memory performance and brain activation in ecstasy polydrug users. A total of 23 abstinent ecstasy polydrug users (age = 24.57 years) and 11 controls (age = 22.36 years) performed a two-part functional magnetic resonance imaging (fMRI) semantic encoding and recognition task. To isolate brain regions activated during each semantic task, we created statistical activation maps in which brain activation was greater for word stimuli than for non-word stimuli (corrected p ecstasy polydrug users had greater activation during semantic encoding bilaterally in language processing regions, including Brodmann areas 7, 39, and 40. Of this bilateral activation, signal intensity with a peak T in the right superior parietal lobe was correlated with lifetime ecstasy use (r s = 0.43, p = 0.042). Behavioral performance did not differ between groups. These findings demonstrate that ecstasy polydrug users have increased brain activation during semantic processing. This increase in brain activation in the absence of behavioral deficits suggests that ecstasy polydrug users have reduced cortical efficiency during semantic encoding, possibly secondary to MDMA-induced 5-HT neurotoxicity. Although pre-existing differences cannot be ruled out, this suggests the possibility of a compensatory mechanism allowing ecstasy polydrug users to perform equivalently to controls, providing additional support for an association of altered cerebral neurophysiology with MDMA exposure.

Methamphetamine and MDMA: ‘Safe’ drugs of abuse

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Allana M. Krolikowski

2014-03-01

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

Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia.

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

2013-02-01

Recreational users report that mephedrone has similar psychoactive effects to 3,4-methylenedioxymethamphetamine (MDMA). MDMA induces well-characterized changes in body temperature due to complex monoaminergic effects on central thermoregulation, peripheral blood flow and thermogenesis, but there are little preclinical data on the acute effects of mephedrone or other synthetic cathinones. The acute effects of cathinone, methcathinone and mephedrone on rectal and tail temperature were examined in individually housed rats, with MDMA included for comparison. Rats were killed 2 h post-injection and brain regions were collected for quantification of 5-HT, dopamine and major metabolites. Further studies examined the impact of selected α-adrenoceptor and dopamine receptor antagonists on mephedrone-induced changes in rectal temperature and plasma catecholamines. At normal room temperature, MDMA caused sustained decreases in rectal and tail temperature. Mephedrone caused a transient decrease in rectal temperature, which was enhanced by α(1) -adrenoceptor and dopamine D(1) receptor blockade, and a prolonged decrease in tail temperature. Cathinone and methcathinone caused sustained increases in rectal temperature. MDMA decreased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) content in several brain regions and reduced striatal homovanillic acid (HVA) levels, whereas cathinone and methcathinone increased striatal HVA and 5-HIAA. Cathinone elevated striatal and hypothalamic 5-HT. Mephedrone elevated plasma noradrenaline levels, an effect prevented by α-adrenoceptor and dopamine receptor antagonists. MDMA and cathinones have different effects on thermoregulation, and their acute effects on brain monoamines also differ. These findings suggest that the adverse effects of cathinones in humans cannot be extrapolated from previous observations on MDMA. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Maternal hair and neonatal meconium to assess gestational consumption and prenatal exposure to drugs of abuse and psychoactive drugs.

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Cortes, Laura; Almeida, Laura; Sabra, Sally; Muniesa, Marta; Busardo, Francesco Paolo; Garcia-Algar, Oscar; Gomez-Roig, Maria Dolores

2018-04-05

In the last two decades, the consumption of drugs of abuse among women of childbearing age has experienced a significant increase and results from analyses of surveys concerning maternal intake of psychoactive prescription drugs during pregnancy indicate that the rates of intake are increasing each year. Analyses of biological matrices such as maternal hair and neonatal meconium have recently been used for assessment of gestational consumption and consequent prenatal exposure to drugs of abuse in high-risk groups of women METHODS: Maternal hair and neonatal meconium were analyzed by validated chromatographic mass spectrometric methodologies to disclose gestational use of drugs of abuse and psychoactive prescription drugs and consequent prenatal exposure in a cohort of 513 mother-newborn dyads at the Sant Joan de Déu Barcelona Hospital, Spain, during 2012- 2013. A total of 3.9% the women reported drugs of abuse or prescription psychoactive drug consumption at any time during pregnancy. The prevalence of gestational consumption and consequent prenatal exposure to drugs of abuse (e.g. cannabis, cocaine and MDMA) was 1.2% in maternal hair and 0.4% in meconium; that of psychoactive prescription drugs (e.g. venlafaxine, citalopram, fluoxetine, clomipramine) was 1.7% in maternal hair and 1.2% in meconium. The prevalence of drugs of abuse and prescription psychoactive drug consumption was lower in our specific cohort of Spanish pregnant women than in other cohorts such as those from U.S. or Denmark. Analysis of materno-fetal matrices provides a viable alternative to study prenatal exposure to these substances and develop specific social and health intervention recommendations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

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Pérez-Hernández, Mercedes; Fernández-Valle, María Encarnación; Rubio-Araiz, Ana; Vidal, Rebeca; Gutiérrez-López, María Dolores; O'Shea, Esther; Colado, María Isabel

2017-05-15

The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X 7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder

NARCIS (Netherlands)

Thal, Sascha B.; Lommen, Miriam J.J.

2018-01-01

The present paper discusses the current literature with regard to substance-assisted psychotherapy with Methylenedioxymethamphetamine (MDMA) for posttraumatic stress disorder (PTSD). The aim of the paper is to give a comprehensive overview of the development from MDMA’s early application in

Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

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Shih, Jui-Hu; Ma, Kuo-Hsing; Chen, Chien-Fu F; Cheng, Cheng-Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng-Yann; Yeh, Ming-Kung; Li, I-Hsun

2016-01-01

The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells.

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Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Rice, Kenner C; Gannon, Brenda M; Fantegrossi, William E; Gonzalez, Carmen; Paule, Merle G; Ali, Syed F

2016-08-26

Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5mM, with similar effects observed after MDPV exposures starting at 1mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced disruption of the endothelial monolayer from 1mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥0.5mM without vacuole formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic. Published by Elsevier Ireland Ltd.

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

Directory of Open Access Journals (Sweden)

Chuang-Hsin Chiu

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

MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

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Rafael eDe La Torre

2012-11-01

Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

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

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Davis, Alan K; Rosenberg, Harold

2014-01-01

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

The effects of 3,4-methylenedioxymethamphetamine (MDMA) on nicotinic receptors: Intracellular calcium increase, calpain/caspase 3 activation, and functional upregulation

International Nuclear Information System (INIS)

Garcia-Rates, Sara; Camarasa, Jordi; Sanchez-Garcia, Ana I.; Gandia, Luis; Escubedo, Elena; Pubill, David

2010-01-01

Previous work by our group demonstrated that homomeric α7 nicotinic acetylcholine receptors (nAChR) play a role in the neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA), as well as the binding affinity of this drug to these receptors. Here we studied the effect of MDMA on the activation of nAChR subtypes, the consequent calcium mobilization, and calpain/caspase 3 activation because prolonged Ca 2+ increase could contribute to cytotoxicity. As techniques, we used fluorimetry in Fluo-4-loaded PC12 cells and electrophysiology in Xenopus oocytes. MDMA produced a rapid and sustained increase in calcium without reaching the maximum effect induced by ACh. It also concentration-dependently inhibited the response induced by ACh, nicotine, and the specific α7 agonist PNU 282987 with IC 50 values in the low micromolar range. Similarly, MDMA induced inward currents in Xenopus oocytes transfected with human α7 but not with α4β2 nAChR and inhibited ACh-induced currents in both receptors in a concentration-dependent manner. The calcium response was inhibited by methyllycaconitine (MLA) and α-bungarotoxin but not by dihydro-β-erythroidine. These results therefore indicate that MDMA acts as a partial agonist on α7 nAChRs and as an antagonist on the heteromeric subtypes. Subsequently, calcium-induced Ca 2+ release from the endoplasmic reticulum and entry through voltage-operated calcium channels are also implicated as proved using specific antagonists. In addition, treatment with MDMA for 24 h significantly increased basal Ca 2+ levels and induced an increase in α-spectrin breakdown products, which indicates that calpain and caspase 3 were activated. These effects were inhibited by pretreatment with MLA. Moreover, pretreatment with MDMA induced functional upregulation of calcium responses to specific agonists of both heteromeric and α7 nAChR. Sustained calcium entry and calpain activation could favor the activation of Ca 2+ -dependent enzymes such as

Depression, impulsiveness, sleep, and memory in past and present polydrug users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).

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Taurah, Lynn; Chandler, Chris; Sanders, Geoff

2014-02-01

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years, and the first to include robust controls for other recreational substances. A sample of 997 participants (52 % male) was recruited to four control groups (non-drug (ND), alcohol/nicotine (AN), cannabis/alcohol/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which, in total, provided 13 psychometric measures. While the CAN and PD groups tended to record greater deficits than the non-drug controls, the MDMA and EX-MDMA groups recorded greater deficits than all the control groups on ten of the 13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98; range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with present ecstasy users, the past users showed no change for ten measures, increased impairment for two measures, and improvement on just one measure. Given this record of impaired memory and clinically significant levels of depression, impulsiveness, and sleep disturbance, the prognosis for the current generation of ecstasy users is a major cause for concern.

Energy intermittency

CERN Document Server

Sorensen, Bent

2014-01-01

The first book to consider intermittency as a key point of an energy system, Energy Intermittency describes different levels of variability for traditional and renewable energy sources, presenting detailed solutions for handling energy intermittency through trade, collaboration, demand management, and active energy storage. Addressing energy supply intermittency systematically, this practical text:Analyzes typical time-distributions and intervals between episodes of demand-supply mismatch and explores their dependence on system layouts and energy source characteristicsSimulates scenarios regar

MDMA-evoked changes in the binding of dopamine D(2) receptor ligands in striatum of rats with unilateral serotonin depletion

DEFF Research Database (Denmark)

Ostergaard, Søren Dinesen; Alstrup, Aage Kristian Olsen; Gramsbergen, Jan Bert

2010-01-01

We earlier reported an anomalous 50% decrease in [(11)C]N-methylspiperone ([(11)C]NMSP) binding to dopamine D(2)-like receptors in living pig striatum after challenge with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), suggesting either (1) a species peculiarity in the vulnerability...... lesions, later verified by [(125)I]RTI-55 autoradiography. Baseline [(11)C]NMSP microPET recordings were followed by either saline or MDMA-HCl (4 mg/kg) injections (i.v.), and a second [(11)C]NMSP recording, culminating with injection of [(3)H]raclopride for autoradiography ex vivo. Neither MDMA......-challenge nor serotonin lesion had any detectable effect on [(11)C]NMSP binding. In contrast, MDMA challenge increased receptor occupancy by [(3)H]raclopride ex vivo (relative to the B(max) in vitro) from 8% to 12%, and doubled the free ligand concentration in cerebral cortex, apparently by blocking hepatic CYP...

MDMA is certainly damaging after 25 years of empirical research: a reply and refutation of Doblin et al. (2014).

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Parrott, Andrew C

2014-03-01

Human Psychopharmacology recently published my review into the increase in empirical knowledge about the human psychobiology of MDMA over the past 25 years (Parrott, 2013a). Deficits have been demonstrated in retrospective memory, prospective memory, higher cognition, complex visual processing, sleep architecture, sleep apnoea, pain, neurohormonal activity, and psychiatric status. Neuroimaging studies have shown serotonergic deficits, which are associated with lifetime Ecstasy/MDMA usage, and degree of neurocognitive impairment. Basic psychological skills remain intact. Ecstasy/MDMA use by pregnant mothers leads to psychomotor impairments in the children. Hence, the damaging effects of Ecstasy/MDMA were far more widespread than was realized a few years ago. In their critique of my review, Doblin et al. (2014) argued that my review contained misstatements, omitted contrary findings, and recited dated misconceptions. In this reply, I have answered all the points they raised. I have been able to refute each of their criticisms by citing the relevant empirical data, since many of their points were based on inaccurate summaries of the actual research findings. Doblin and colleagues are proponents of the use of MDMA for drug-assisted psychotherapy, and their strongest criticisms were focused on my concerns about this proposal. However, again all the issues I raised were based on sound empirical evidence or theoretical understanding. Indeed I would recommend potentially far safer co-drugs such as D-cycloserine or oxytocin. In summary, MDMA can induce a wide range of neuropsychobiological changes, many of which are damaging to humans. Copyright © 2014 John Wiley & Sons, Ltd.

MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder.

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Bouso, José Carlos; Doblin, Rick; Farré, Magí; Alcázar, Miguel Angel; Gómez-Jarabo, Gregorio

2008-09-01

The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.

No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation.

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Kuypers, Kim P C; de la Torre, Rafael; Farre, Magi; Yubero-Lahoz, Samanta; Dziobek, Isabel; Van den Bos, Wouter; Ramaekers, Johannes G

2014-01-01

The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial registration: MDMA & PSB NTR 2636.

No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation.

Directory of Open Access Journals (Sweden)

Kim P C Kuypers

Full Text Available The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg, with or without pindolol (20 mg, oxytocin nasal spray (40 IU+16 IU or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial registration: MDMA & PSB NTR 2636.

No Evidence that MDMA-Induced Enhancement of Emotional Empathy Is Related to Peripheral Oxytocin Levels or 5-HT1a Receptor Activation

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Kuypers, Kim P. C.; de la Torre, Rafael; Farre, Magi; Yubero-Lahoz, Samanta; Dziobek, Isabel; Van den Bos, Wouter; Ramaekers, Johannes G.

2014-01-01

The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18–26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial Registration MDMA & PSB NTR 2636 PMID:24972084

Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"): preliminary findings

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Reneman, L.; Lavalaye, J.; Schmand, B.; de Wolff, F. A.; van den Brink, W.; den Heeten, G. J.; Booij, J.

2001-01-01

BACKGROUND: Although the popular drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to damage brain serotonin (5-HT) neurons in animals, the fate and functional consequences of 5-HT neurons after MDMA injury are not known in humans. We investigated the long-term effects of

New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain.

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Shokry, Ibrahim M; Callanan, John J; Sousa, John; Tao, Rui

2016-01-01

In spite of the fact that systemic administration of MDMA elicits serotonin syndrome, direct intracranial administration fails to reproduce the effect. To reconcile these findings, it has been suggested that the cause of serotonin syndrome is attributed mainly to MDMA hepatic metabolites, and less likely to MDMA itself. Recently, however, this explanation has been challenged, and alternative hypotheses need to be explored. Here, we tested the hypothesis that serotonin syndrome is the result of excessive 5HT simultaneously in many brain areas, while MDMA administered intracranially fails to cause serotonin syndrome because it produces only a localized effect at the delivery site and not to other parts of the brain. This hypothesis was examined using adult male Sprague Dawley rats by comparing 5HT responses in the right and left hemispheric frontal cortices, right and left hemispheric diencephalons, and medullar raphe nucleus. Occurrence of serotonin syndrome was confirmed by measuring change in body temperature. Administration routes included intraperitoneal (IP), intracerebroventricular (ICV) and reverse microdialysis. First, we found that IP administration caused excessive 5HT in all five sites investigated and induced hypothermia, suggesting the development of the serotonin syndrome. In contrast, ICV and reverse microdialysis caused excessive 5HT only in regions of delivery sites without changes in body-core temperature, suggesting the absence of the syndrome. Next, chemical dyes were used to trace differences in distribution and diffusion patterns between administration routes. After systemic administration, the dyes were found to be evenly distributed in the brain. However, the dyes administered through ICV or reverse microdialysis injection still remained in the delivery sites, poorly diffusing to the brain. In conclusion, intracranial MDMA administration in one area has no or little effect on other areas, which must be considered a plausible reason for the

New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain.

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Ibrahim M Shokry

Full Text Available In spite of the fact that systemic administration of MDMA elicits serotonin syndrome, direct intracranial administration fails to reproduce the effect. To reconcile these findings, it has been suggested that the cause of serotonin syndrome is attributed mainly to MDMA hepatic metabolites, and less likely to MDMA itself. Recently, however, this explanation has been challenged, and alternative hypotheses need to be explored. Here, we tested the hypothesis that serotonin syndrome is the result of excessive 5HT simultaneously in many brain areas, while MDMA administered intracranially fails to cause serotonin syndrome because it produces only a localized effect at the delivery site and not to other parts of the brain. This hypothesis was examined using adult male Sprague Dawley rats by comparing 5HT responses in the right and left hemispheric frontal cortices, right and left hemispheric diencephalons, and medullar raphe nucleus. Occurrence of serotonin syndrome was confirmed by measuring change in body temperature. Administration routes included intraperitoneal (IP, intracerebroventricular (ICV and reverse microdialysis. First, we found that IP administration caused excessive 5HT in all five sites investigated and induced hypothermia, suggesting the development of the serotonin syndrome. In contrast, ICV and reverse microdialysis caused excessive 5HT only in regions of delivery sites without changes in body-core temperature, suggesting the absence of the syndrome. Next, chemical dyes were used to trace differences in distribution and diffusion patterns between administration routes. After systemic administration, the dyes were found to be evenly distributed in the brain. However, the dyes administered through ICV or reverse microdialysis injection still remained in the delivery sites, poorly diffusing to the brain. In conclusion, intracranial MDMA administration in one area has no or little effect on other areas, which must be considered a plausible

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

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

2016-04-01

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

Prenatal Diagnosis

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Ozge Ozalp Yuregir

2012-02-01

Full Text Available Prenatal diagnosis is the process of determining the health or disease status of the fetus or embryo before birth. The purpose is early detection of diseases and early intervention when required. Prenatal genetic tests comprise of cytogenetic (chromosome assessment and molecular (DNA mutation analysis tests. Prenatal testing enables the early diagnosis of many diseases in risky pregnancies. Furthermore, in the event of a disease, diagnosing prenatally will facilitate the planning of necessary precautions and treatments, both before and after birth. Upon prenatal diagnosis of some diseases, termination of the pregnancy could be possible according to the family's wishes and within the legal frameworks. [Archives Medical Review Journal 2012; 21(1.000: 80-94

Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats.

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Lopez-Rodriguez, Ana Belen; Llorente-Berzal, Alvaro; Garcia-Segura, Luis M; Viveros, Maria-Paz

2014-03-01

Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Δ(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA. Adolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6. © 2013 The British Pharmacological Society.

Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

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Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

2012-01-01

Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

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

DEFF Research Database (Denmark)

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

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

Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

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Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

2012-01-01

Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users

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Frokjaer, Vibe Gedsoe; Erritzoe, David; Holst, Klaus Kähler

2014-01-01

awakening response (CAR). Here, we tested (1) if such a correlation persists in a human model of chronic serotonin depletion, namely in 3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') users, and (2) if CAR differed between MDMA users (N = 18) and non-using healthy volunteers (N = 32). Participants...... underwent SERT brain imaging with [11C]DASB-PET, and performed home-sampling of CAR, defined as the area under curve with respect to cortisol increase from awakening level. When adjusting for age and group, CAR was positively coupled to prefrontal SERT binding (p = 0.006) and MDMA users showed significantly...... higher CAR than the control group (p = 0.0003). In conclusion, our data confirm the recently described positive association between prefrontal SERT binding and CAR, this time in a human model of serotonin deficiency. Also, we find that CAR was higher in MDMA users relative to non-users. We suggest...

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

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

2016-04-03

A combination of cannabis and ecstasy may change the cognitive functions more than either drug alone. The present study was designed to investigate the possible involvement of dorsal hippocampal NMDA receptors in the interactive effects of arachidonylcyclopropylamide (ACPA) and ecstasy/MDMA on memory retrieval. Adult male Wistar rats were cannulated into the CA1 regions of the dorsal hippocampus (intra-CA1) and memory retrieval was examined using the step-through type of passive avoidance task. Intra-CA1 microinjection of a selective CB1 receptor agonist, ACPA (0.5-4ng/rat) immediately before the testing phase (pre-test), but not after the training phase (post-training), impaired memory retrieval. In addition, pre-test intra-CA1 microinjection of MDMA (0.5-1μg/rat) dose-dependently decreased step-through latency, indicating an amnesic effect of the drug by itself. Interestingly, pre-test microinjection of a higher dose of MDMA into the CA1 regions significantly improved ACPA-induced memory impairment. Moreover, pre-test intra-CA1 microinjection of a selective NMDA receptor antagonist, D-AP5 (1 and 2μg/rat) inhibited the reversal effect of MDMA on the impairment of memory retrieval induced by ACPA. Pre-test intra-CA1 microinjection of the same doses of D-AP5 had no effect on memory retrieval alone. These findings suggest that ACPA or MDMA consumption can induce memory retrieval impairment, while their co-administration improves this amnesic effect through interacting with hippocampal glutamatergic-NMDA receptor mechanism. Thus, it seems that the tendency to abuse cannabis with ecstasy may be for avoiding cognitive dysfunction. Copyright © 2015. Published by Elsevier Inc.

A clinical plan for MDMA (Ecstasy) in the treatment of posttraumatic stress disorder (PTSD): partnering with the FDA.

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Doblin, Rick

2002-01-01

The FDA and the Spanish Ministry of Health have concluded that the risk/benefit ratio is favorable under certain circumstances for clinical studies investigating MDMA-assisted psychotherapy. Both agencies have approved pilot studies in chronic posttraumatic stress disorder (PTSD) patients who have failed to obtain relief from at least one course of conventional treatment. These studies, the only ones in the world into the therapeutic use of MDMA, are being funded by a nonprofit research and educational organization, the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org). A rationale is offered explaining why MAPS chose to focus its limited resources on MDMA, and also on PTSD patients. A Clinical Plan is elaborated for the conduct of the "adequate and well-controlled" trials necessary to evaluate the safety and efficacy of MDMA-assisted psychotherapy for PTSD, with the studies estimated to cost about 5 million dollars and to take about five years. The Clinical Plan has been developed, in part, through analysis of the studies conducted by Pfizer in its successful effort to have Zoloft approved by the FDA for use with PTSD patients, and through review of transcripts of the FDA's Psychopharmacologic Drugs Advisory Committee meeting that recommended approval of Zoloft for PTSD.

Gender differences in hyperthermia and regional 5-HT and 5-HIAA depletion in the brain following MDMA administration in rats

NARCIS (Netherlands)

Wallinga, Alinde E.; Grahlmann, Carolin; Granneman, Ramon A.; Koolhaas, Jaap M.; Buwalda, Bauke

2011-01-01

In the present research the role of gender in MDMA-induced hyperthermia and serotonin depletion is studied by injecting male and female male rats with MDMA or saline 3 times (i.p.) with 3 h interval at dosages of 0.3, 1, 3 or 9 mg/kg at an ambient temperature of 25 degrees C. The acute hyperthermia

The Effects of Ecstasy (MDMA) on Brain Serotonin Transporters Are Dependent on Age-of-First Exposure in Recreational Users and Animals

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Klomp, Anne; den Hollander, Bjørnar; de Bruin, Kora; Booij, Jan; Reneman, Liesbeth

2012-01-01

Objective: Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin) exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are

Intermittent search strategies

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Bénichou, O.; Loverdo, C.; Moreau, M.; Voituriez, R.

2011-01-01

This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. It is first shown that intermittent search strategies are actually widely observed at various scales. At the macroscopic scale, this is, for example, the case of animals looking for food; at the microscopic scale, intermittent transport patterns are involved in a reaction pathway of DNA-binding proteins as well as in intracellular transport. Second, generic stochastic models are introduced, which show that intermittent strategies are efficient strategies that enable the minimization of search time. This suggests that the intrinsic efficiency of intermittent search strategies could justify their frequent observation in nature. Last, beyond these modeling aspects, it is proposed that intermittent strategies could also be used in a broader context to design and accelerate search processes.

Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

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Vivian Capilla-Gonzalez

2011-06-01

Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

Group prenatal care.

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Mazzoni, Sara E; Carter, Ebony B

2017-06-01

Patients participating in group prenatal care gather together with women of similar gestational ages and 2 providers who cofacilitate an educational session after a brief medical assessment. The model was first described in the 1990s by a midwife for low-risk patients and is now practiced by midwives and physicians for both low-risk patients and some high-risk patients, such as those with diabetes. The majority of literature on group prenatal care uses CenteringPregnancy, the most popular model. The first randomized controlled trial of CenteringPregnancy showed that it reduced the risk of preterm birth in low-risk women. However, recent meta-analyses have shown similar rates of preterm birth, low birthweight, and neonatal intensive care unit admission between women participating in group prenatal care and individual prenatal care. There may be subgroups, such as African Americans, who benefit from this type of prenatal care with significantly lower rates of preterm birth. Group prenatal care seems to result in increased patient satisfaction and knowledge and use of postpartum family planning as well as improved weight gain parameters. The literature is inconclusive regarding breast-feeding, stress, depression, and positive health behaviors, although it is theorized that group prenatal care positively affects these outcomes. It is unclear whether group prenatal care results in cost savings, although it may in large-volume practices if each group consists of approximately 8-10 women. Group prenatal care requires a significant paradigm shift. It can be difficult to implement and sustain. More randomized trials are needed to ascertain the true benefits of the model, best practices for implementation, and subgroups who may benefit most from this innovative way to provide prenatal care. In short, group prenatal care is an innovative and promising model with comparable pregnancy outcomes to individual prenatal care in the general population and improved outcomes in some

Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.

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

2016-12-01

The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of

Inhibition potential of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites on the in vitro monoamine oxidase (MAO)-catalyzed deamination of the neurotransmitters serotonin and dopamine.

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Steuer, Andrea E; Boxler, Martina I; Stock, Lorena; Kraemer, Thomas

2016-01-22

Neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) is still controversially discussed. Formation of reactive oxygen species e.g. based on elevated dopamine (DA) concentrations and DA quinone formation is discussed among others. Inhibition potential of MDMA metabolites regarding neurotransmitter degradation by catechol-O-methyltransferase and sulfotransferase was described previously. Their influence on monoamine oxidase (MAO) - the major DA degradation pathway-has not yet been studied in humans. Therefore the inhibition potential of MDMA and its metabolites on the deamination of the neurotransmitters DA and serotonin (5-HT) by MAO-A and B using recombinant human enzymes in vitro should be investigated. In initial studies, MDMA and MDA showed relevant inhibition (>30%) toward MAO A for 5-HT and DA. No relevant effects toward MAO B were observed. Further investigation on MAO-A revealed MDMA as a competitive inhibitor of 5-HT and DA deamination with Ki 24.5±7.1 μM and 18.6±4.3 μM respectively and MDA as a mixed-type inhibitor with Ki 7.8±2.6 μM and 8.4±3.2 μM respectively. Although prediction of in vivo relevance needs to be done with care, relevant inhibitory effects at expected plasma concentrations after recreational MDMA consumption seems unlikely based on the obtained data. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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

2015-09-01

3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA's neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously. © The Author(s) 2015.

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

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

2016-01-01

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

Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects.

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Reneman, Liesbeth; de Win, Maartje M L; van den Brink, Wim; Booij, Jan; den Heeten, Gerard J

2006-03-01

Users of ecstasy (3,4-methylenedioxymethamphetamine; MDMA) may be at risk of developing MDMA-induced injury to the serotonin (5-HT) system. Previously, there were no methods available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivoneuroimaging tools have begun to provide insights into the effects of ecstasy on the human brain. Single photon emission computed tomography (SPECT), positron emission computed tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS) studies which have evaluated ecstasy's neurotoxic potential will be reviewed and discussed in terms of technical aspects, conceptual issues and future prospects. Although PET and SPECT may be limited by several factors such as the low cortical uptake and the use of a non-optimal reference region (cerebellum) the few studies conducted so far provide suggestive evidence that people who heavily use ecstasy are at risk of developing subcortical, and probably also cortical reductions in serotonin transporter (SERT) densities, a marker of 5-HT neurotoxicity. There seem to be dose-dependent and transient reductions in SERT for which females may be more vulnerable than males. 1H-MRS appears to be a less sensitive technique for studying ecstasy's neurotoxic potential. Whether individuals with a relatively low ecstasy exposure also demonstrate loss of SERT needs to be determined. Because most studies have had a retrospective design, in which evidence is indirect and differs in the degree to which any causal links can be implied, longitudinal studies in human ecstasy users are needed to draw definite conclusions.

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

Science.gov (United States)

Steuer, Andrea E; Schmidhauser, Corina; Tingelhoff, Eva H; Schmid, Yasmin; Rickli, Anna; Kraemer, Thomas; Liechti, Matthias E

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Andrea E Steuer

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

Prenatal Methamphetamine Exposure Linked with Problems

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... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

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

Science.gov (United States)

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

2014-03-01

Parrott recently published a review of literature on MDMA/ecstasy. This commentary is a response to the content and tenor of his review, which mischaracterizes the literature through misstatement and omission of contrary findings, and fails to address the central controversies in the literature. The review makes several erroneous statements concerning MDMA-assisted psychotherapy, such as incorrect statements about research design and other statements that are baseless or contradicted by the literature. Though it critiques an attempt by other authors to characterize the risks of MDMA, the review fails to produce a competing model of risk assessment, and does not discuss potential benefits. Parrott does not represent an even-handed review of the literature, but instead recites dated misconceptions about neurotoxicity concerns involving the recreational drug ecstasy, which do not relate directly to the use of pure MDMA in a therapeutic setting. Unchallenged, Parrott's report may deter researchers from further investigating an innovative treatment that in early clinical trials has demonstrated lasting benefits for people with chronic, treatment-resistant post-traumatic stress disorder. Copyright © 2014 John Wiley & Sons, Ltd.

Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory.

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Scholey, A B; Owen, L; Gates, J; Rodgers, J; Buchanan, T; Ling, J; Heffernan, T; Swan, P; Stough, C; Parrott, A C

2011-01-01

Our group has conducted several Internet investigations into the biobehavioural effects of self-reported recreational use of MDMA (3,4-methylenedioxymethamphetamine or Ecstasy) and other psychosocial drugs. Here we report a new study examining the relationship between self-reported Ecstasy use and traces of MDMA found in hair samples. In a laboratory setting, 49 undergraduate volunteers performed an Internet-based assessment which included mood scales and the University of East London Drug Use Questionnaire, which asks for history and current drug use. They also provided a hair sample for determination of exposure to MDMA over the previous month. Self-report of Ecstasy use and presence in hair samples were consistent (p happiness and higher self-reported stress. Self-reported Ecstasy use, but not presence in hair, was also associated with decreased tension. Different psychoactive drugs can influence long-term mood and cognition in complex and dynamically interactive ways. Here we have shown a good correspondence between self-report and objective assessment of exposure to MDMA. These data suggest that the Internet has potentially high utility as a useful medium to complement traditional laboratory studies into the sequelae of recreational drug use. Copyright © 2010 S. Karger AG, Basel.

Bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young male patient following MDMA intake.

Science.gov (United States)

Obiechina, Nonyelum Evangeline; Jayakumar, Ahrane; Khan, Yusra; Bass, James

2018-04-07

MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is an illicit drug frequently used by young people at parties and 'raves'. It is readily available in spite of the fact that it is illegal. 1 It is perceived by a lot of young people as being 'harmless', but there have been a few high-profile deaths associated with its use. 2 Known side effects of MDMA include hyperthermia, rhabdomyolysis, coagulopathy and cardiac arrhythmias. 3 Rarer side effects include surgical emphysema and pneumomediastinum, which have been better described with cocaine abuse. 4-6 We present a case of bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young man after taking ecstasy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prenatal Tests

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... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

Opioid gene expression changes and post-translational histone modifications at promoter regions in the rat nucleus accumbens after acute and repeated 3,4-methylenedioxy-methamphetamine (MDMA) exposure.

Science.gov (United States)

Caputi, Francesca Felicia; Palmisano, Martina; Carboni, Lucia; Candeletti, Sanzio; Romualdi, Patrizia

2016-12-01

The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been shown to produce neurotoxic damage and long-lasting changes in several brain areas. In addition to the involvement of serotoninergic and dopaminergic systems, little information exists about the contribution of nociceptin/orphaninFQ (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by MDMA. Here we investigated the behavioral and molecular effects induced by acute (8mg/kg) or repeated (8mg/kg twice daily for seven days) MDMA exposure. MDMA exposure affected body weight gain and induced hyperlocomotion; this latter effect progressively decreased after repeated administration. Gene expression analysis indicated a down-regulation of the N/OFQ system and an up-regulation of the DYN system in the nucleus accumbens (NAc), highlighting an opposite systems regulation in response to MDMA exposure. Since histone modifications have been strongly associated to the addiction-related maladaptive changes, we examined two permissive (acH3K9 and me3H3K4) and two repressive transcription marks (me3H3K27 and me2H3K9) at the pertinent opioid gene promoter regions. Chromatin immunoprecipitation assays revealed that acute MDMA increased me3H3K4 at the pN/OFQ, pDYN and NOP promoters. Following acute and repeated treatment a significant decrease of acH3K9 at the pN/OFQ promoter was observed, which correlated with gene expression results. Acute treatment caused an acH3K9 increase and a me2H3K9 decrease at the pDYN promoter which matched its mRNA up-regulation. Our data indicate that the activation of the DYNergic stress system together with the inactivation of the N/OFQergic anti-stress system contribute to the neuroadaptive actions of MDMA and offer novel epigenetic information associated with MDMA abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

OpenAIRE

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

2007-01-01

A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-beta-methyl-beta-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to t...

MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.

Science.gov (United States)

Kiyatkin, Eugene A; Ren, Suelynn E

2017-01-01

Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential

Identification and quantitation of 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) in human urine by 1H NMR spectroscopy. Application to five cases of intoxication.

Science.gov (United States)

Liu, Jonathan; Decatur, John; Proni, Gloria; Champeil, Elise

2010-01-30

Identification of 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) in five cases of intoxication using nuclear magnetic resonance (NMR) spectroscopy of human urine is reported. A new water suppression technique PURGE (Presaturation Utilizing Relaxation Gradients and Echoes) was used. A calibration curve was obtained using spiked samples. The method gave a linear response (correlation coefficient of 0.992) over the range 0.01-1mg/mL. Subsequently, quantitation of the amount of MDMA present in the samples was performed. The benefit and reliability of NMR investigations of human urine for cases of intoxication with MDMA are discussed. Published by Elsevier Ireland Ltd.

Diagnóstico Prenatal

OpenAIRE

López, Jaime Octavio; Saldarriaga, Wilmar; Fundación Valle de Lili

2010-01-01

Diagnóstico Prenatal/ propósitos del diagnóstico prenatal/ Tamizaje a partir del Control Prenatal/ Pacientes de bajo riesgo/ Tamizaje bioquímico/ Pacientes de alto riesgo/ Pruebas invasivas y no invasivas

Intermittent degradation and schizotypy

Directory of Open Access Journals (Sweden)

Matthew W. Roché

2015-06-01

Full Text Available Intermittent degradation refers to transient detrimental disruptions in task performance. This phenomenon has been repeatedly observed in the performance data of patients with schizophrenia. Whether intermittent degradation is a feature of the liability for schizophrenia (i.e., schizotypy is an open question. Further, the specificity of intermittent degradation to schizotypy has yet to be investigated. To address these questions, 92 undergraduate participants completed a battery of self-report questionnaires assessing schizotypy and psychological state variables (e.g., anxiety, depression, and their reaction times were recorded as they did so. Intermittent degradation was defined as the number of times a subject’s reaction time for questionnaire items met or exceeded three standard deviations from his or her mean reaction time after controlling for each item’s information processing load. Intermittent degradation scores were correlated with questionnaire scores. Our results indicate that intermittent degradation is associated with total scores on measures of positive and disorganized schizotypy, but unrelated to total scores on measures of negative schizotypy and psychological state variables. Intermittent degradation is interpreted as potentially derivative of schizotypy and a candidate endophenotypic marker worthy of continued research.

[Prenatal care in Latin America].

Science.gov (United States)

Buekens, P; Hernández, P; Infante, C

1990-01-01

Available data on the coverage of prenatal care in Latin America were reviewed. In recent years, only Bolivia had a coverage of prenatal care of less than 50 per cent. More than 90 per cent of pregnant women received prenatal care in Chile, Cuba, the Dominican Republic, and Puerto Rico. Prenatal care increased between the 1970 and 1980 in the Dominican Republic, Ecuador, Guatemala, Honduras, Mexico, and Peru. The coverage of prenatal care decreased in Bolivia and Colombia. The mean number of visits increased in Cuba and Puerto Rico. The increase of prenatal care in Guatemala and Honduras is due to increased care by traditional birth attendants, compared to the role of health care institutions. We compared the more recent data on tetanus immunization of pregnant women to the more recent data on prenatal care. The rates of tetanus immunization are always lower than the rates of prenatal care attendance, except in Costa Rica. The rates of tetanus immunization was less than half as compared to the rates of prenatal care in Bolivia, Guatemala, and Peru. To improve the content of prenatal care should be an objective complementary to the increase of the number of attending women.

Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder

OpenAIRE

Thal, Sascha B.; Lommen, Miriam J.J.

2018-01-01

The present paper discusses the current literature with regard to substance-assisted psychotherapy with Methylenedioxymethamphetamine (MDMA) for posttraumatic stress disorder (PTSD). The aim of the paper is to give a comprehensive overview of the development from MDMA’s early application in psychotherapy to its present and future role in the treatment of PTSD. It is further attempted to increase the attention for MDMA’s therapeutic potential by providing a thorough depiction of the scientific...

Symptoms of anxiety and depression in childhood and use of MDMA: prospective, population based study

NARCIS (Netherlands)

A.C. Huizink (Anja); R.F. Ferdinand (Robert); J. van der Ende (Jan); F.C. Verhulst (Frank)

2006-01-01

textabstractOBJECTIVE: To investigate whether using ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is preceded by symptoms of behavioural and emotional problems in childhood and early adolescence. DESIGN: Prospective, longitudinal, population based study SETTING: The Dutch

The Role of MDMA (Ecstasy) in Coping with Negative Life Situations Among Urban Young Adults

Science.gov (United States)

Moonzwe, Lwendo S.; Schensul, Jean J.; Kostick, Kristin M.

2011-01-01

This article examines the role of Ecstasy (MDMA or 3, 4-methylenedioxymethamphetamine) as a drug used for self-medication and coping with both short- and long-term negative life situations. We show that urban youth who do not have a specific diagnosed mental illness are more likely than those who have been diagnosed and have received treatment to use Ecstasy to cope with both situational stress and lifetime trauma. Diagnosed and treated youth sometimes self-medicate with other drugs, but do not choose Ecstasy for mediation of their psychological stress. We discuss the implications of self-medication with Ecstasy for mental health services to urban youth experiencing mental health disparities, and for the continued testing and prescription of MDMA for therapeutic use in controlled clinical settings. PMID:22111403

Symptoms of anxiety and depression in childhood and use of MDMA: prospective, population based study

NARCIS (Netherlands)

Huizink, A.C.; Ferdinand, R.F.; Ende, J. van den; Verhulst, F.C.

2006-01-01

Objective To investigate whether using ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is preceded by symptoms of behavioural and emotional problems in childhood and early adolescence. Design Prospective, longitudinal, population based study. Setting The Dutch province of

A High-Resolution Magic Angle Spinning NMR Study of the Enantiodiscrimination of 3,4-Methylenedioxymethamphetamine (MDMA by an Immobilized Polysaccharide-Based Chiral Phase.

Directory of Open Access Journals (Sweden)

Juliana C Barreiro

Full Text Available This paper reports the investigation of the chiral interaction between 3,4-methylenedioxy-methamphetamine (MDMA enantiomers and an immobilized polysaccharide-based chiral phase. For that, suspended-state high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (1H HR-MAS NMR was used. 1H HR-MAS longitudinal relaxation time and Saturation Transfer Difference (STD NMR titration experiments were carried out yielding information at the molecular level of the transient diastereoisomeric complexes of MDMA enantiomers and the chiral stationary phase. The interaction of the enantiomers takes place through the aromatic moiety of MDMA and the aromatic group of the chiral selector by π-π stacking for both enantiomers; however, a stronger interaction was observed for the (R-enantiomer, which is the second one to elute at the chromatographic conditions.

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

NARCIS (Netherlands)

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

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

Cocaine, MDMA and methamphetamine residues in wastewater: Consumption trends (2009-2015) in South East Queensland, Australia.

Science.gov (United States)

Lai, Foon Yin; O'Brien, Jake W; Thai, Phong K; Hall, Wayne; Chan, Gary; Bruno, Raimondo; Ort, Christoph; Prichard, Jeremy; Carter, Steve; Anuj, Shalona; Kirkbride, K Paul; Gartner, Coral; Humphries, Melissa; Mueller, Jochen F

2016-10-15

Wastewater analysis, or wastewater-based epidemiology, has become a common tool to monitor trends of illicit drug consumption around the world. In this study, we examined trends in cocaine, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine consumption by measuring their residues in wastewater from two wastewater treatment plants in Australia (specifically, an urban and a rural catchment, both in South East Queensland) between 2009 and 2015. With direct injection of the samples, target analytes were identified and quantified using liquid chromatography-mass spectrometry. Cocaine and MDMA residues and metabolites were mainly quantifiable in the urban catchment while methamphetamine residues were consistently detected in both urban and rural catchments. There was no consistent trend in the population normalised mass loads observed for cocaine and MDMA at the urban site between 2009 and 2015. In contrast, there was a five-fold increase in methamphetamine consumption over this period in this catchment. For methamphetamine consumption, the rural area showed a very similar trend as the urban catchment starting at a lower baseline. The observed increase in per capita loads of methamphetamine via wastewater analysis over the past six years in South East Queensland provides objective evidence for increased methamphetamine consumption in the Australian population while the use of other illicit stimulants remained relatively stable. Copyright © 2016 Elsevier B.V. All rights reserved.

The Prenatal Care at School Program

Science.gov (United States)

Griswold, Carol H.; Nasso, Jacqueline T.; Swider, Susan; Ellison, Brenda R.; Griswold, Daniel L.; Brooks, Marilyn

2013-01-01

School absenteeism and poor compliance with prenatal appointments are concerns for pregnant teens. The Prenatal Care at School (PAS) program is a new model of prenatal care involving local health care providers and school personnel to reduce the need for students to leave school for prenatal care. The program combines prenatal care and education…

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-07-23

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

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

Science.gov (United States)

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

2007-07-23

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

Prenatal Care Checkup

Science.gov (United States)

... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

Intermittent Explosive Disorder

Directory of Open Access Journals (Sweden)

Lut Tamam

2011-09-01

Full Text Available Intermittent explosive disorder is an impulse control disorder characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Though the prevalence intermittent explosive disorder has been reported to be relatively rare in frontier studies on the field, it is now common opinion that intermittent explosive disorder is far more common than previously thought especially in clinical psychiatry settings. Etiological studies displayed the role of both psychosocial factors like childhood traumas and biological factors like dysfunctional neurotransmitter systems and genetics. In differential diagnosis of the disorder, disorders involving agression as a symptom such as alcohol and drug intoxication, antisocial and borderline personality disorders, personality changes due to general medical conditions and behavioral disorder should be considered. A combination of pharmacological and psychotherapeutic approaches are suggested in the treatment of the disorder. This article briefly reviews the historical background, diagnostic criteria, epidemiology, etiology and treatment of intermittent explosive disorder.

Preconception Care and Prenatal Care

Science.gov (United States)

... Twitter Pinterest Email Print About Preconception Care and Prenatal Care What is preconception care? Preconception care is the ... improve the health of your child. What is prenatal care? Prenatal care is the health care a woman ...

Findings on prenatal, lactational and later childhood exposure to dioxins and dioxin-like compounds: a review of the Amsterdam-Zaandam cohort 1987–2005

Directory of Open Access Journals (Sweden)

Gavin W. ten Tusscher

2015-02-01

Full Text Available The Amsterdam-Zaandam cohort has been studied intermittently since 1987. The cohort was selected for optimal pregnancy and birth, in whom prenatal, lactational and more recently current dioxin exposures were measured. In the perinatal period and during the years thereafter, effects on various organ systems have been documented: thyroid, metabolism, immunity, haematology, motor development, brain development, lung function and puberty. We present a review of the endpoints studied, from the perinatal period into adolescence.

Mechanisms and environmental factors that underlying the intensification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced serotonin syndrome in rats

Science.gov (United States)

Tao, Rui; Shokry, Ibrahim M.; Callanan, John J.; Adams, H. Daniel; Ma, Zhiyuan

2014-01-01

Rationale Illicit use of MDMA (3,4-methylenedioxymethamphetamine; Ecstasy) may cause a mild or severe form of the serotonin syndrome. The syndrome intensity is not just influenced by drug doses but also by environmental factors. Objectives Warm environmental temperatures and physical activity are features of raves. The purpose of this study was to assess how these two factors can potentially intensify the syndrome. Methods Rats were administered MDMA at doses of 0.3, 1 or 3 mg/kg, and examined in the absence or presence of warm temperature and physical activity. The syndrome intensity was estimated by visual scoring for behavioral syndrome and also instrumentally measuring changes in symptoms of the syndrome. Results Our results showed that MDMA at 3 mg/kg, but not 0.3 or 1 mg/kg, caused a mild serotonin syndrome in rats. Each environmental factor alone moderately intensified the syndrome. When the two factors were combined, the intensification became more severe than each factor alone highlighting a synergistic effect. This intensification was blocked by the 5-HT2A receptor antagonist M100907, competitive NMDA receptor antagonist CGS19755, autonomic ganglionic blocker hexamethonium, and the benzodiazepine-GABAA receptor agonist midazolam, but not by the 5-HT1A receptor antagonist WAY100635 or nicotinic receptor antagonist methyllycaconitine. Conclusions Our data suggest that, in the absence of environmental factors, the MDMA-induced syndrome is mainly mediated through the serotonergic transmission (5HT-dependent mechanism), and therefore, is relatively mild. Warm temperature and physical activity facilitate serotonergic and other neural systems such as glutamatergic and autonomic transmissions, resulting in intensification of the syndrome (non-5HT mechanisms). PMID:25300903

Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

Science.gov (United States)

Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

2008-04-01

The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

Intermittent heating of buildings

Energy Technology Data Exchange (ETDEWEB)

Kohonen, K

1983-02-01

Conditions for intermittent heating of buildings are considered both theoretically and experimentally. Thermal behaviour of buildings adn rooms in intermittent heating is simulated by a program based on the convective heat balance equation and by simplified RC-models. The preheat times and the heating energy savings compared with continuous heating are presented for typical lightweight, mediumweight and heavyweight classroom and office modules. Formulaes for estimating the oversizing of the radiator network, the maximum heat output of heat exchangers in district heating and the efficiency of heating boilers in intermittent heating are presented. The preheat times and heating energy savings with different heating control systems are determined also experimentally in eight existing buildings. In addition some principles for the planning and application of intermittent heating systems are suggested.

Multidimensional intermittency in hadronic collisions

International Nuclear Information System (INIS)

Pan, J.; Hwa, R.C.

1992-06-01

The study of intermittency in high-energy hadronic collisions by the Monte Carlo code ECCO is extended to 3-dimensional phase space. Strong intermittency is found in agreement with the data. Fluctuation in the impact parameter is responsible for the intermittency in lnp T , and the transverse-momentum conservation leads to negative intermittency slopes in the azimuthal angle φ. The Ochs-Wosiek plots are linear in all dimensions having universal slopes. An exponent ν = 1.448 emerges to characterize multiparticle production in pp collisions. The properties of G moments are also examined, and the fractal dimensions determined

Does offering prenatal screening influence pregnant women's attitudes regarding prenatal testing?

NARCIS (Netherlands)

Kleinveld, J.H.; van den Berg, M.; van Eijk, J.T.; van Vugt, J.M.G.; van der Wal, G.; Timmermans, D.R.M.

2008-01-01

Objectives: This study aims to find out whether offering prenatal screening for Down syndrome and neural tube defects influences pregnant women's attitudes toward having a screening test. Methods: Women were randomised into a group that was offered prenatal screening and a group that was not offered

Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring.

Science.gov (United States)

Bolton, Jessica L; Auten, Richard L; Bilbo, Staci D

2014-03-01

Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1β response to an LPS challenge at postnatal day (P)30, whereas their central IL-1β response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner. Copyright © 2013 Elsevier Inc. All rights reserved.

Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

Science.gov (United States)

Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

2011-08-01

To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P 50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit. © RSNA, 2011.

Methaemoglobinemia Induced by MDMA?

Directory of Open Access Journals (Sweden)

L. L. W. Verhaert

2011-01-01

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

The external gate of the human and Drosophila serotonin transporters requires a basic/acidic amino acid pair for 3,4-methylenedioxymethamphetamine (MDMA) translocation and the induction of substrate efflux.

Science.gov (United States)

Sealover, Natalie R; Felts, Bruce; Kuntz, Charles P; Jarrard, Rachel E; Hockerman, Gregory H; Lamb, Patrick W; Barker, Eric L; Henry, L Keith

2016-11-15

The substituted amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy), is a widely used drug of abuse that induces non-exocytotic release of serotonin, dopamine, and norepinephrine through their cognate transporters as well as blocking the reuptake of neurotransmitter by the same transporters. The resulting dramatic increase in volume transmission and signal duration of neurotransmitters leads to psychotropic, stimulant, and entactogenic effects. The mechanism by which amphetamines drive reverse transport of the monoamines remains largely enigmatic, however, promising outcomes for the therapeutic utility of MDMA for post-traumatic stress disorder and the long-time use of the dopaminergic and noradrenergic-directed amphetamines in treatment of attention-deficit hyperactivity disorder and narcolepsy increases the importance of understanding this phenomenon. Previously, we identified functional differences between the human and Drosophila melanogaster serotonin transporters (hSERT and dSERT, respectively) revealing that MDMA is an effective substrate for hSERT but not dSERT even though serotonin is a potent substrate for both transporters. Chimeric dSERT/hSERT transporters revealed that the molecular components necessary for recognition of MDMA as a substrate was linked to regions of the protein flanking transmembrane domains (TM) V through IX. Here, we performed species-scanning mutagenesis of hSERT, dSERT and C. elegans SERT (ceSERT) along with biochemical and electrophysiological analysis and identified a single amino acid in TM10 (Glu394, hSERT; Asn484, dSERT, Asp517, ceSERT) that is primarily responsible for the differences in MDMA recognition. Our findings reveal that an acidic residue is necessary at this position for MDMA recognition as a substrate and serotonin releaser. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Feyza Bora

2016-11-01

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

Prenatal care: associations with prenatal depressive symptoms and social support in low-income urban women.

Science.gov (United States)

Sidebottom, Abbey C; Hellerstedt, Wendy L; Harrison, Patricia A; Jones-Webb, Rhonda J

2017-10-01

We examined associations of depressive symptoms and social support with late and inadequate prenatal care in a low-income urban population. The sample was prenatal care patients at five community health centers. Measures of depressive symptoms, social support, and covariates were collected at prenatal care entry. Prenatal care entry and adequacy came from birth certificates. We examined outcomes of late prenatal care and less than adequate care in multivariable models. Among 2341 study participants, 16% had elevated depressive symptoms, 70% had moderate/poor social support, 21% had no/low partner support, 37% had late prenatal care, and 29% had less than adequate prenatal care. Women with both no/low partner support and elevated depressive symptoms were at highest risk of late care (AOR 1.85, CI 1.31, 2.60, p care (AOR 0.74, CI 0.54, 1.10, p = 0.051). Women with moderate/high depressive symptoms were less likely to experience less than adequate care compared to women with low symptoms (AOR 0.73, CI 0.56, 0.96, p = 0.022). Social support and partner support were negatively associated with indices of prenatal care use. Partner support was identified as protective for women with depressive symptoms with regard to late care. Study findings support public health initiatives focused on promoting models of care that address preconception and reproductive life planning. Practice-based implications include possible screening for social support and depression in preconception contexts.

Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques

DEFF Research Database (Denmark)

Mardal, Marie; Kinyua, Juliet; Ramin, Pedram

2017-01-01

were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene...... (CE) had 85–102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% ± 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA....... The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd....

Intermittency in branching models

International Nuclear Information System (INIS)

Chiu, C.B.; Texas Univ., Austin; Hwa, R.C.; Oregon Univ., Eugene

1990-01-01

The intermittency properties of three branching models have been investigated. The factorial moments show power-law behavior as function of small rapidity width. The slopes and energy dependences reveal different characteristics of the models. The gluon model has the weakest intermittency. (orig.)

Prenatal screening and genetics

DEFF Research Database (Denmark)

Alderson, P; Aro, A R; Dragonas, T

2001-01-01

Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

Validity of in vivo [123I]beta-CIT SPECT in detecting MDMA-induced neurotoxicity in rats

NARCIS (Netherlands)

de Win, Maartje M. L.; de Jeu, Rogier A. M.; de Bruin, Kora; Habraken, Jan B. A.; Reneman, Liesbeth; Booij, Jan; den Heeten, Gerard J.

2004-01-01

This study investigated the ability of a high-resolution pinhole single-photon emission computed tomography (SPECT) system, with [(123)I]beta-CIT as a radiotracer, to detect 3,4-methelenedioxymethamphetamine (MDMA, 'Ecstasy')-induced loss of serotonin transporters (SERTs) in the living rat brain. In

Metabolic Effects of Intermittent Fasting.

Science.gov (United States)

Patterson, Ruth E; Sears, Dorothy D

2017-08-21

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

Prenatal stress may increase vulnerability to life events comparison with the effects of prenatal dexamethasone

DEFF Research Database (Denmark)

Hougaard, Karin; Andersen, Maibritt B; Kjaer, Sanna L

2005-01-01

naïve at the time of ASR testing, whereas the other had been through blood sampling for assessment of the hormonal stress response to restraint, 3 months previously. Both prenatal CMS and dexamethasone increased ASR in the offspring compared to controls, but only in prenatally stressed offspring......Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...... of the acoustic startle response. Further, a single aversive life event showed capable of changing the reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this event. This suggests that circumstances dating back to the very...

5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine.

Science.gov (United States)

Colado, M I; Murray, T K; Green, A R

1993-03-01

1. The present study has investigated whether the neurotoxic effects of the relatively selective 5-hydroxytryptamine (5-HT) neurotoxins, 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'), p-chloroamphetamine (PCA) and fenfluramine on hippocampal and cortical 5-HT terminals in rat brain could be prevented by administration of either chlormethiazole or dizocilpine. 2. Administration of MDMA (20 mg kg-1, i.p.) resulted in an approximate 30% loss of cortical and hippocampal 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content 4 days later. Injection of chlormethiazole (50 mg kg-1) 5 min before and 55 min after the MDMA provided complete protection in both regions, while dizocilpine (1 mg kg-1, i.p.) protected only the hippocampus. 3. Administration of a single dose of chlormethiazole (100 mg kg-1) 20 min after the MDMA also provided complete protection to the hippocampus but not the cortex. This regime also attenuated the sustained hyperthermia (approx +2.5 degrees C) induced by the MDMA injection. 4. Injection of PCA (5 mg kg-1, i.p.) resulted in a 70% loss of 5-HT and 5-HIAA content in hippocampus and cortex 4 days later. Injection of chlormethiazole (100 mg kg-1, i.p.) or dizocilpine (1 mg kg-1, i.p.) 5 min before and 55 min after the PCA failed to protect against the neurotoxicity, nor was protection afforded by chlormethiazole when a lower dose of PCA (2.5 mg kg-1, i.p.) was given which produced only a 30% loss of 5-HT content. Chlormethiazole did prevent the hyperthermia induced by PCA (5 mg kg-1), while the lower dose of PCA (2.5 mg kg-1) did not produce a change in body temperature.5. Neither chlormethiazole nor dizocilpine prevented the neurotoxic loss of hippocampal or cortical 5-HT neurones measured 4 days following administration of fenfluramine (25 mg kg-1, i.p.).6. In general, chlormethiazole and dizocilpine were effective antagonists of the 5-HT-mediated behaviours of head weaving and forepaw treading which appeared following injection of all three

Cosmic Rays in Intermittent Magnetic Fields

International Nuclear Information System (INIS)

Shukurov, Anvar; Seta, Amit; Bushby, Paul J.; Wood, Toby S.; Snodin, Andrew P.

2017-01-01

The propagation of cosmic rays in turbulent magnetic fields is a diffusive process driven by the scattering of the charged particles by random magnetic fluctuations. Such fields are usually highly intermittent, consisting of intense magnetic filaments and ribbons surrounded by weaker, unstructured fluctuations. Studies of cosmic-ray propagation have largely overlooked intermittency, instead adopting Gaussian random magnetic fields. Using test particle simulations, we calculate cosmic-ray diffusivity in intermittent, dynamo-generated magnetic fields. The results are compared with those obtained from non-intermittent magnetic fields having identical power spectra. The presence of magnetic intermittency significantly enhances cosmic-ray diffusion over a wide range of particle energies. We demonstrate that the results can be interpreted in terms of a correlated random walk.

Cosmic Rays in Intermittent Magnetic Fields

Energy Technology Data Exchange (ETDEWEB)

Shukurov, Anvar; Seta, Amit; Bushby, Paul J.; Wood, Toby S. [School of Mathematics and Statistics, Newcastle University, Newcastle Upon Tyne NE1 7RU (United Kingdom); Snodin, Andrew P., E-mail: a.seta1@ncl.ac.uk, E-mail: amitseta90@gmail.com [Department of Mathematics, Faculty of Applied Science, King Mongkut’s University of Technology North Bangkok, Bangkok 10800 (Thailand)

2017-04-10

The propagation of cosmic rays in turbulent magnetic fields is a diffusive process driven by the scattering of the charged particles by random magnetic fluctuations. Such fields are usually highly intermittent, consisting of intense magnetic filaments and ribbons surrounded by weaker, unstructured fluctuations. Studies of cosmic-ray propagation have largely overlooked intermittency, instead adopting Gaussian random magnetic fields. Using test particle simulations, we calculate cosmic-ray diffusivity in intermittent, dynamo-generated magnetic fields. The results are compared with those obtained from non-intermittent magnetic fields having identical power spectra. The presence of magnetic intermittency significantly enhances cosmic-ray diffusion over a wide range of particle energies. We demonstrate that the results can be interpreted in terms of a correlated random walk.

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy

OpenAIRE

Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick

2017-01-01

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of ?openness? occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of c...

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

NARCIS (Netherlands)

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

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

Prenatal anxiety effects: A review.

Science.gov (United States)

Field, Tiffany

2017-11-01

This review is based on literature on prenatal anxiety effects that was found on Pubmed and PsycINFO for the years 2010-2016. Prenatal anxiety is thought to have distinct features, although it has been measured both by specific prenatal anxiety symptoms as well as by standardized anxiety scales. Its prevalence has ranged from 21 to 25% and it has been predicted by a number of pregnancy - related variables such as unintended pregnancy, demographic variables such as low acculturation and income and psychosocial factors including pessimism and partner tension. Prenatal anxiety effects on pregnancy include increased cortisol levels, pro-inflammatory cytokines, obstetric problems and cesarean section. Effects on the neonate include lower gestational age, prematurity, less insulin-like growth factor in cord blood, less exclusive breast-feeding and less self-regulation during the heelstick procedure. Prenatal anxiety effects continue into infancy and childhood both on physiological development and emotional/mental development. Among the physiological effects are lower vagal activity across the first two years, and lower immunity, more illnesses and reduced gray matter in childhood. Prenatal anxiety effects on emotional/mental development include greater negative emotionality and in infants, lower mental development scores and internalizing problems. Anxiety disorders occur during childhood and elevated cortisol and internalizing behaviors occur during adolescence. Interventions for prenatal anxiety are virtually nonexistent, although stroking (massaging) the infant has moderated the pregnancy - specific anxiety effects on internalizing behaviors in the offspring. The limitations of this literature include the homogeneity of samples, the frequent use of anxiety measures that are not specific to pregnancy, and the reliance on self-report. Nonetheless, the literature highlights the negative, long-term effects of prenatal anxiety and the need for screening and early

Developing electrodes chemically modified with cucurbit[6]uril to detect 3,4-methylenedioxymethamphetamine (MDMA) by voltammetry

International Nuclear Information System (INIS)

Tadini, Maraine Catarina; Balbino, Marco Antonio; Eleoterio, Izabel Cristina; Siqueirade Oliveira, Laura; Dias, Luis Gustavo; Jean-François Demets, Grégoire; Firmino de Oliveira, Marcelo

2014-01-01

Graphical abstract: - Highlights: • A new stand in forensic chemistry. • Voltammetric method for the determination of MDMA in seized samples. • A new voltammetric sensor for MDMA. - Abstract: This study aimed to develop an electrode chemically modified with cucurbit[6]uril to detect 3,4-methylenedioxymethamphetamine (MDMA), the main active principle of ecstasy samples, by voltammetry. We modified the electrode surface with a film containing cucurbit[6]uril, Nafion, and methanol, using the dip coating or the spin coating technique. During analysis, we employed an electrochemical cell with a conventional three-electrode system and KCl solution (0.1 mol L −1 ) as the supporting electrolyte. We conducted cyclic voltammetry at concentrations ranging from 4.2 × 10 −6 to 4.8 × 10 −5 mol L −1 . We also accomplished scanning electron microscopy, to investigate the structural behavior of the film that originated on the electrode surface. We obtained the following results when we used dip coating to prepare the modified electrode: standard deviation (SD) = 0.024 μA, limit of detection (LOD) = 3.5 μmol L −1 , limit of quantification (LOQ) = 11.7 μmol L −1 , and amperometric sensitivity (m) = 20.9 × 10 3 μA L mol −1 . As for spin coating, we obtained SD = 0.024 μA, LOD = 2.7 μmol L −1 , LOQ = 9.1 μmol L −1 and m = 25.9 × 10 3 μA mol L −1 . These are very promising data: the modified electrode is more sensitive than the conventional glassy carbon electrode under the studied experimental conditions

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

Science.gov (United States)

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Prenatal vitamins: what is in the bottle?

Science.gov (United States)

Duerbeck, Norman B; Dowling, David D; Duerbeck, Jillinda M

2014-12-01

Nearly all obstetricians routinely prescribe prenatal vitamins to their pregnant patients at the time of the first prenatal visit. Many times, patients' understanding of the health benefits of prenatal vitamins differs substantially from that of the prescribing physician. The following is a review of the most common ingredients found in prenatal vitamins and their purported health benefits.

Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants.

Science.gov (United States)

Reyes, Zenaida C; Claure, Nelson; Tauscher, Markus K; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo

2006-10-01

Prolonged mechanical ventilation is associated with lung injury in preterm infants. In these infants, weaning from synchronized intermittent mandatory ventilation may be delayed by their inability to cope with increased respiratory loads. The addition of pressure support to synchronized intermittent mandatory ventilation can offset these loads and may facilitate weaning. The purpose of this work was to compare synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in weaning from mechanical ventilation and the duration of supplemental oxygen dependency in preterm infants with respiratory failure. Preterm infants weighing 500 to 1000 g at birth who required mechanical ventilation during the first postnatal week were randomly assigned to synchronized intermittent mandatory ventilation or synchronized intermittent mandatory ventilation plus pressure support. In both groups, weaning followed a set protocol during the first 28 days. Outcomes were assessed during the first 28 days and until discharge or death. There were 107 infants enrolled (53 synchronized intermittent mandatory ventilation plus pressure support and 54 synchronized intermittent mandatory ventilation). Demographic and perinatal data, mortality, and morbidity did not differ between groups. During the first 28 days, infants in the synchronized intermittent mandatory ventilation plus pressure support group reached minimal ventilator settings and were extubated earlier than infants in the synchronized intermittent mandatory ventilation group. Total duration of mechanical ventilation, duration of oxygen dependency, and oxygen need at 36 weeks' postmenstrual age alone or combined with death did not differ between groups. However, infants in synchronized intermittent mandatory ventilation plus pressure support within the 700- to 1000-g birth weight strata had a shorter oxygen dependency. The results of this study suggest that the addition of

Genes Underlying Positive Influence Of Prenatal Environmental ...

African Journals Online (AJOL)

Genes Underlying Positive Influence Of Prenatal Environmental Enrichment And ... Prenatal environmental enrichment (EE) has been proven to positively affect but ... Conclusion: The negative-positive prenatal effect could contribute to altered ...

Prenatal Care: New Hampshire Residents - 1976.

Science.gov (United States)

Mires, Maynard H.; Sirc, Charles E.

Data from 1976 New Hampshire birth certificates were used to examine the correlations between the degree (month of pregnancy that prenatal care began) and intensity (number of prenatal visits) of prenatal care and low infant birth weight, illegitimacy, maternal age, maternal education, and complications of pregnancy. The rate of low birth weight…

Intermittency in 197Au fragmentation

International Nuclear Information System (INIS)

Dabrowska, A.; Holynski, R.; Olszewski, A.; Szarska, M.; Wilczynska, B.; Wolter, W.; Wosiek, B.; Cherry, M.L.; Deines-Jones, P.; Jones, W.V.; Sengupta, K.; Wefel, B.

1995-07-01

The concept of factorial moments was applied to an analysis of the dynamical fluctuations in the charge distributions of the fragments emitted from gold nuclei with energies 10.6 and < 1.0 GeV/n interacting with emulsion nuclei. Clear evidence for intermittent fluctuations has been found in an analysis using all the particles released from the gold projectile, with a stronger effect observed below 1 GeV/n than at 10.6 GeV/n. For the full data sets, however, the intermittency effect was found to be very sensitive to the singly charged particles, and neglecting these particles strongly reduces the intermittency signal. When the analysis is restricted to the multiply charged fragments, an intermittency effect is revealed only for multifragmentation events, although one that is enhanced as compared to the analysis of all, singly and multiply charged, particles. The properties of the anomalous fractal dimensions suggest a sequential decay mechanism, rather than the existence of possible critical behaviour in the process of nuclear fragmentation. The likely influence of the charge conservation effects and the finite size of decaying systems on the observed intermittency signals was pointed out. (author). 37 refs, 9 figs, 5 tabs

Neurodevelopmental Outcomes of Prenatal Stress

Directory of Open Access Journals (Sweden)

M. Genco Usta

2012-03-01

Full Text Available The influence of prenatal stress on psychopathology has been observed in many animal and human studies. In many studies, stress during prenatal period has been shown to result in negative feedback dysregulation and hyperactivity of hypothalamo-pituitary-adrenocortical axis. Prenatal stres also may cause increased risk of birth complications, startle or distress in response to novel and surprising stimuli during infancy; lower Full Scale IQs, language abilities and attention deficiency in period of 3-5 years; increased risk of attention deficit hyperactivity syndrome, anxiety symptoms, depressive disorder and impulsivity during adolescence. Additionally, timing of prenatal stress is also important and 12-22 weeks of gestation seems to be the most vulnerable period. The results underline the need for early prevention and intervention programs for highly anxious women during pregnancy. Administration of prenatal stress monitoring to public health programs or removing pregnant women who have been exposed to life events such as natural disaster, terror attack to secure areas that provide basic needs may be crucial.

Barriers to adequate prenatal care utilization in American Samoa

Science.gov (United States)

Hawley, Nicola L; Brown, Carolyn; Nu’usolia, Ofeira; Ah-Ching, John; Muasau-Howard, Bethel; McGarvey, Stephen T

2013-01-01

Objective To describe the utilization of prenatal care in American Samoan women and to identify socio-demographic predictors of inadequate prenatal care utilization. Methods Using data from prenatal clinic records, women (n=692) were categorized according to the Adequacy of Prenatal Care Utilization Index as having received adequate plus, adequate, intermediate or inadequate prenatal care during their pregnancy. Categorical socio-demographic predictors of the timing of initiation of prenatal care (week of gestation) and the adequacy of received services were identified using one way Analysis of Variance (ANOVA) and independent samples t-tests. Results Between 2001 and 2008 85.4% of women received inadequate prenatal care. Parity (P=0.02), maternal unemployment (P=0.03), and both parents being unemployed (P=0.03) were negatively associated with the timing of prenatal care initation. Giving birth in 2007–2008, after a prenatal care incentive scheme had been introduced in the major hospital, was associated with earlier initiation of prenatal care (20.75 versus 25.12 weeks; Pprenatal care utilization in American Samoa is a major concern. Improving healthcare accessibility will be key in encouraging women to attend prenatal care. The significant improvements in the adequacy of prenatal care seen in 2007–2008 suggest that the prenatal care incentive program implemented in 2006 may be a very positive step toward addressing issues of prenatal care utilization in this population. PMID:24045912

Intermittent control: a computational theory of human control.

Science.gov (United States)

Gawthrop, Peter; Loram, Ian; Lakie, Martin; Gollee, Henrik

2011-02-01

The paradigm of continuous control using internal models has advanced understanding of human motor control. However, this paradigm ignores some aspects of human control, including intermittent feedback, serial ballistic control, triggered responses and refractory periods. It is shown that event-driven intermittent control provides a framework to explain the behaviour of the human operator under a wider range of conditions than continuous control. Continuous control is included as a special case, but sampling, system matched hold, an intermittent predictor and an event trigger allow serial open-loop trajectories using intermittent feedback. The implementation here may be described as "continuous observation, intermittent action". Beyond explaining unimodal regulation distributions in common with continuous control, these features naturally explain refractoriness and bimodal stabilisation distributions observed in double stimulus tracking experiments and quiet standing, respectively. Moreover, given that human control systems contain significant time delays, a biological-cybernetic rationale favours intermittent over continuous control: intermittent predictive control is computationally less demanding than continuous predictive control. A standard continuous-time predictive control model of the human operator is used as the underlying design method for an event-driven intermittent controller. It is shown that when event thresholds are small and sampling is regular, the intermittent controller can masquerade as the underlying continuous-time controller and thus, under these conditions, the continuous-time and intermittent controller cannot be distinguished. This explains why the intermittent control hypothesis is consistent with the continuous control hypothesis for certain experimental conditions.

Prenatal Care: Third Trimester Visits

Science.gov (United States)

... Pregnancy week by week During the third trimester, prenatal care might include vaginal exams to check the baby's position. By Mayo Clinic Staff Prenatal care is an important part of a healthy pregnancy, ...

Agony of the ecstasy: report of five cases of MDMA smuggling.

Science.gov (United States)

Low, V H S; Dillon, E K

2005-10-01

The international smuggling of illicit drugs by the ingestion or rectal insertion of drug-filled packages is recognized in the trafficking of heroin and cocaine. Customs authorities, with suspicion of such activities, presented five subjects. The legally allowed radiological examination comprising one supine abdominal radiograph was performed. Radiographic findings demonstrated the presence of multiple enteric oval, capsule-shaped packages of soft tissue density. This was confirmed following supervised evacuation of bowel contents induced by the administration of laxatives. Analysis of the concealed material identified ecstasy (methylenedioxymethamphetamine (MDMA)), a substance not previously reported as transported by this route.

CONDITIONED ANALYSIS OF HIGH-LATITUDE SOLAR WIND INTERMITTENCY

International Nuclear Information System (INIS)

D'Amicis, R.; Consolini, G.; Bavassano, B.; Bruno, R.

2012-01-01

The solar wind is a turbulent medium displaying intermittency. Its intermittent features have been widely documented and studied, showing how the intermittent character is different in fast and slow wind. In this paper, a statistical conditioned analysis of the solar wind intermittency for a period of high-latitude fast solar wind is presented. In particular, the intermittent features are investigated as a function of the Alfvénic degree of fluctuations at a given scale. The results show that the main contribution to solar wind intermittency is due to non-Alfvénic structures, while Alfvénic increments are found to be characterized by a smaller level of intermittency than the previous ones. Furthermore, the lifetime statistics of Alfvénic periods are discussed in terms of a multiscale texture of randomly oriented flux tubes.

Prenatal Care: Second Trimester Visits

Science.gov (United States)

... Pregnancy week by week During the second trimester, prenatal care includes routine lab tests and measurements of your ... too. By Mayo Clinic Staff The goal of prenatal care is to ensure that you and your baby ...

Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex.

Science.gov (United States)

Bose, Sonali; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Di, Qian; Rosa, Maria José; Lee, Alison; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Wright, Robert O; Cohen, Sheldon; Coull, Brent A; Wright, Rosalind J

2017-12-01

Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. We implemented Bayesian-distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO 3 - ) on child asthma, accounting for effect modification by sex and stress. Analyses included 752 mother-child dyads. Daily ambient NO 3 - exposure during pregnancy was derived using a hybrid chemical transport (Geos-Chem)/land-use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician-diagnosed asthma by age 6 years. Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7-19 and 33-40 wk gestation), during which increased NO 3 - was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO 3 - across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27-5.39; per interquartile range increase in ln NO 3 - ). Prenatal NO 3 - exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.

Intermittency '93

International Nuclear Information System (INIS)

Bialas, A.

1993-01-01

The existing data definitely indicate the existence of intermittency, i.e. of self similar structures in the systems of particles created in high-energy collisions. The effect seems universal: it was found in most of the processes investigated and its measures parameters depend only weakly (if at all) on the process in question. Strong HBT effect was found, suggesting that intermittency is related to space-time structure of the pion source rather than to detailed momentum structure of the production amplitudes. There are indications that this space time structure may be fractal, but more data is needed to establish this. The theoretical explanation remains obscure: it seems that both parton cascade and hadronization play an important role. Their interrelation, however, remains a mystery. 5 figs., 19 refs

Prenatal Genetic Counseling (For Parents)

Science.gov (United States)

... Videos for Educators Search English Español Prenatal Genetic Counseling KidsHealth / For Parents / Prenatal Genetic Counseling What's in ... can they help your family? What Is Genetic Counseling? Genetic counseling is the process of: evaluating family ...

Eugenesia y diagnóstico prenatal

OpenAIRE

González Salvat, Rosa María; González Labrador, Ignacio

2002-01-01

El uso del diagnóstico prenatal en la práctica de la genética médica ha hecho que se recuerden teorías eugenésicas. Se realizó una revisión histórica de este término y se relacionó con el uso del diagnóstico prenatal (DPN) y el aborto selectivo a la luz de los conocimientos bioéticos actuales. The use of the prenatal diagnosis in the practice of medical genetics has led us to remember eugenic theories. A historical review of this term was made and it was connected with the use of prenatal ...

Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

Science.gov (United States)

Yau, Mabel; Khattab, Ahmed; New, Maria I

2016-06-01

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. Copyright © 2016 Elsevier Inc. All rights reserved.

Congenital lung malformations: correlation between prenatal and ...

African Journals Online (AJOL)

Aim: Congenital lung malformations are a common finding during prenatal ultrasonography (US). Investigations were completed by means of prenatal MRI and postnatal computed tomographic (CT) scan. The purpose of this study was to compare these prenatal findings with postnatal findings and pathological findings after ...

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

Science.gov (United States)

Lyvers, Michael; Meester, Molly

2012-01-01

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

Impact of Combined Prenatal Ethanol and Prenatal Stress Exposures on Markers of Activity-Dependent Synaptic Plasticity in Rat Dentate Gyrus

OpenAIRE

Staples, Miranda C.; Porch, Morgan W.; Savage, Daniel D.

2014-01-01

Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression o...

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

Science.gov (United States)

Zeiler, Frederick A; Donnelly, Joseph; Calviello, Leanne; Menon, David K; Smielewski, Peter; Czosnyka, Marek

2017-12-01

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO 2 ) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE ® , BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO 2 (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of

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

Directory of Open Access Journals (Sweden)

José Luiz da Costa

2009-01-01

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

Prenatal Care: First Trimester Visits

Science.gov (United States)

... care provider will discuss the importance of proper nutrition and prenatal vitamins. Your first prenatal visit is a good time to discuss exercise, sex during pregnancy and other lifestyle issues. You might also discuss your work environment and the use of medications during pregnancy. If ...

Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening

NARCIS (Netherlands)

van Schendel, Rachèl V.; Kleinveld, Johanna H.; Dondorp, Wybo J.; Pajkrt, Eva; Timmermans, Danielle R. M.; Holtkamp, Kim C. A.; Karsten, Margreet; Vlietstra, Anne L.; Lachmeijer, Augusta M. A.; Henneman, Lidewij

2014-01-01

Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The

ACOG Committee Opinion No. 731: Group Prenatal Care.

Science.gov (United States)

2018-03-01

Individual prenatal care is intended to prevent poor perinatal outcomes and provide education to women throughout pregnancy, childbirth, and the postpartum period through a series of one-on-one encounters between a woman and her obstetrician or other obstetric care provider. Concerns regarding increasing health care costs, health care provider availability, dissatisfaction with wait times, and the minimal opportunity for education and support associated with the individual care model have given rise to interest in alternative models of prenatal care. One alternative model, group prenatal care, may be beneficial or preferred for some practice settings and patient populations, although individual prenatal care remains standard practice. Group prenatal care models are designed to improve patient education and include opportunities for social support while maintaining the risk screening and physical assessment of individual prenatal care. Bringing patients with similar needs together for health care encounters increases the time available for the educational component of the encounter, improves efficiency, and reduces repetition. Evidence suggests patients have better prenatal knowledge, feel more ready for labor and delivery, are more satisfied with care in prenatal care groups, and initiate breastfeeding more often. There is no evidence that suggests that group prenatal care causes harm. Individual and group care models warrant additional study with a goal of demonstrating differences in outcomes and identifying populations that benefit most from specific care models.

Self-Reported Ecstasy/MDMA/"Molly" Use in a Sample of Nightclub and Dance Festival Attendees in New York City.

Science.gov (United States)

Palamar, Joseph J; Acosta, Patricia; Ompad, Danielle C; Cleland, Charles M

2017-01-02

Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of "Molly," which is often marketed as pure MDMA. Surveys have generally not included "Molly" in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use-nightlife attendees. We surveyed 679 young adults (age 18-25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR = 0.37, p = .015). Over a third of ecstasy users (36.8%)reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones ["bath salts"]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name).

Optimal intermittent search strategies

International Nuclear Information System (INIS)

Rojo, F; Budde, C E; Wio, H S

2009-01-01

We study the search kinetics of a single fixed target by a set of searchers performing an intermittent random walk, jumping between different internal states. Exploiting concepts of multi-state and continuous-time random walks we have calculated the survival probability of a target up to time t, and have 'optimized' (minimized) it with regard to the transition probability among internal states. Our model shows that intermittent strategies always improve target detection, even for simple diffusion states of motion

Prenatal Testing: MedlinePlus Health Topic

Science.gov (United States)

... Dept. of Health and Human Services Office on Women's Health Start Here Prenatal Tests (Nemours Foundation) Also in Spanish Prenatal Tests (March of Dimes Birth Defects Foundation) Also in Spanish ...

Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats.

Science.gov (United States)

Thomas, Jennifer D; Idrus, Nirelia M; Monk, Bradley R; Dominguez, Hector D

2010-10-01

Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development. Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring. Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task. These data indicate that choline supplementation during prenatal alcohol exposure may reduce the severity of fetal alcohol effects, particularly on alterations in tasks that require behavioral flexibility. These findings have important implications for children of women who drink alcohol during pregnancy. © 2010 Wiley-Liss, Inc.

Prenatal and Postnatal Management of Hydronephrosis

Science.gov (United States)

Rao, Pravin K.; Palmer, Jeffrey S.

2009-01-01

The majority of pregnant women in the U.S. undergo prenatal ultrasonography and approximately 0.5% of these examinations will detect fetal malformations. Up to one-half of these abnormalities include the genitourinary system and the most common urological finding is hydronephrosis. Some conditions associated with prenatal hydronephrosis portend a poor prognosis, while others can follow a fairly benign course. This review focuses on the definition and prenatal assessment of hydronephrosis, fetal intervention, and postnatal management. PMID:19618087

Intermittency in {sup 197}Au fragmentation

Energy Technology Data Exchange (ETDEWEB)

Dabrowska, A; Holynski, R; Olszewski, A; Szarska, M; Wilczynska, B; Wolter, W; Wosiek, B [Institute of Nuclear Physics, Cracow (Poland); Cherry, M L; Deines-Jones, P; Jones, W V; Sengupta, K; Wefel, B [Louisiana State Univ., Baton Rouge, LA (United States). Dept. of Physics and Astronomy; Waddington, C J [Minnesota Univ., Minneapolis, MN (United States). School of Physics and Astronomy; Pozharova, E A; Skorodko, T Yu [Inst. of Theoretical and Experimental Physics, Moscow (Russian Federation); KLMM Collaboration

1995-07-01

The concept of factorial moments was applied to an analysis of the dynamical fluctuations in the charge distributions of the fragments emitted from gold nuclei with energies 10.6 and < 1.0 GeV/n interacting with emulsion nuclei. Clear evidence for intermittent fluctuations has been found in an analysis using all the particles released from the gold projectile, with a stronger effect observed below 1 GeV/n than at 10.6 GeV/n. For the full data sets, however, the intermittency effect was found to be very sensitive to the singly charged particles, and neglecting these particles strongly reduces the intermittency signal. When the analysis is restricted to the multiply charged fragments, an intermittency effect is revealed only for multifragmentation events, although one that is enhanced as compared to the analysis of all, singly and multiply charged, particles. The properties of the anomalous fractal dimensions suggest a sequential decay mechanism, rather than the existence of possible critical behaviour in the process of nuclear fragmentation. The likely influence of the charge conservation effects and the finite size of decaying systems on the observed intermittency signals was pointed out. (author). 37 refs, 9 figs, 5 tabs.

Prenatal diagnosis of horseshoe lung and esophageal atresia

International Nuclear Information System (INIS)

Goldberg, Shlomit; Ringertz, Hans; Barth, Richard A.

2006-01-01

We present a case of horseshoe lung (HL) and esophageal atresia suspected prenatally on US imaging and confirmed with fetal MRI. Prenatal diagnosis of HL and esophageal atresia allowed for prenatal counseling and informed parental decisions. (orig.)

Prenatal diagnosis of horseshoe lung and esophageal atresia

Energy Technology Data Exchange (ETDEWEB)

Goldberg, Shlomit; Ringertz, Hans [Stanford University School of Medicine, Radiology Department, Stanford, CA (United States); Barth, Richard A. [Stanford University School of Medicine, Radiology Department, Stanford, CA (United States); Lucile Packard Children' s Hospital, Radiology, Palo Alto, CA (United States)

2006-09-15

We present a case of horseshoe lung (HL) and esophageal atresia suspected prenatally on US imaging and confirmed with fetal MRI. Prenatal diagnosis of HL and esophageal atresia allowed for prenatal counseling and informed parental decisions. (orig.)

Prenatal ultrasonographic findings of cloacal anomaly

Energy Technology Data Exchange (ETDEWEB)

Song, Mi Jin [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2002-09-15

To evaluate the ultrasonographic characteristic of a rare malformation comples, Cloacal anomaly on prenatal ultrasonography. From March 1991 to July 2001, eight cases with the persistent cloaca (4 cases in female and 1 case in male) and cloacal exstrophy (3 cases) diagnosed by prenatal ultrasound examination were included, and all of them were pathologically confirmed by autopsy. One radiologist retrospectively analyzed the prenatal sonographic images, including the urinary bladder, kidney, pelvic cyst, abdominal wall defect and amount of amniotic fluid. The ultrasonographic diagnosis was established at 21.8 {+-} 7.8 weeks of gestation. The prenatal ultrasonographic findings of the persistent cloaca were absent bladder (n=2), distended bladder (n=2) and small thick bladder (n=1). Sonography of the kidney showed normal (n=2), hydronephrosis (n=1), dysplasia (n=1) and unilateral hydronephrosis with absent contralateral kidney (n=1). Four fetuses showed septated pelvic cyst; three fetuses, oligohydramnios. The prenatal ultrasonographic findings of cloacal exstrophy included absent bladder (n=3), normal kidney (n=1), hydronephrosis (n=1) and absent kidney (n=1). All fetuses with cloacal exstrophy had abdominal wall defect while two of them had oligohydramnios. A prenatal diagnosis of persistent cloaca can be confidently made when there is septated pelvic cyst combined oligohydramnios, sediments within the cyst and intraluminal calcifications. Cloacal exstrophy should be included in diagnosis if there is a low abdominal wall defect with absent urinary bladder.

Optimal intermittent search strategies

Energy Technology Data Exchange (ETDEWEB)

Rojo, F; Budde, C E [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, X5000HUA Cordoba (Argentina); Wio, H S [Instituto de Fisica de Cantabria, Universidad de Cantabria and CSIC E-39005 Santander (Spain)

2009-03-27

We study the search kinetics of a single fixed target by a set of searchers performing an intermittent random walk, jumping between different internal states. Exploiting concepts of multi-state and continuous-time random walks we have calculated the survival probability of a target up to time t, and have 'optimized' (minimized) it with regard to the transition probability among internal states. Our model shows that intermittent strategies always improve target detection, even for simple diffusion states of motion.

Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep

OpenAIRE

Padmanabhan, Vasantha; Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit

2015-01-01

Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insuli...

Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure.

Science.gov (United States)

Kirsten, Thiago B; Queiroz-Hazarbassanov, Nicolle; Bernardi, Maria M; Felicio, Luciano F

2015-06-01

Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS),which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism.We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia.Materials and methods:We evaluated the effects of LPS and zinc on female reproductive performance. Communication,which is impaired in autism,was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker.Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction.Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls.Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments.The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway.

Should prenatal hydronephrosis that resolves before birth be followed postnatally? Analysis and comparison to persistent prenatal hydronephrosis.

Science.gov (United States)

Scarborough, Patrick L; Ferrara, Elizabeth; Storm, Douglas W

2015-09-01

Prenatal ultrasonography has greatly enhanced detection of congenital genitourinary abnormalities. However, although persistent prenatal hydronephrosis (PPH) is typically imaged and followed postnatally, it remains unclear if prenatal hydronephrosis that resolves in utero (RPH) should be similarly managed. We determined postnatal abnormalities associated with RPH and compared these to those associated with PPH. We performed a retrospective review of all consecutive patients evaluated for prenatal hydronephrosis over 24 months. Patients were followed prenatally with serial ultrasounds and postnatally with ultrasonography and a voiding cystourethrogram. Of the consecutive 165 patients enrolled in the study, 72 had RPH. The average prenatal anterior-posterior renal pelvis length was significantly longer in patients with PPH (5.5 mm) than in those with RPH (4.9 mm) (p = 0.01). Recurrent postnatal hydronephrosis occurred in 44% of patients with RPH, with eventual resolution in 34% of those affected. In comparison, 29% of PPH cases resolved postnatally. Mean time to resolution was statistically shorter for PPH (116 days) than for RPH (175 days) (p = 0.01). Seven PPH patients required surgery, while no RPH patients needed intervention (difference was statistically significant). A significant number of RPH children had postnatal hydronephrosis. Despite a slower resolution time, no children with RPH required intervention. Although RPH may recur postnatally, the significantly lower chance of intervention being required suggests that these children may not require postnatal imaging.

Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances.

Science.gov (United States)

Kopelman, M D; Reed, L J; Marsden, P; Mayes, A R; Jaldow, E; Laing, H; Isaac, C

2001-01-01

A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered.

Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep.

Science.gov (United States)

Padmanabhan, Vasantha; Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit

2015-07-01

Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insulin sensitizer, rosiglitazone; 5) prenatal T and postnatal flutamide; 6) prenatal T and postnatal rosiglitazone; and 7) prenatal T and postnatal metformin. Prenatal treatments spanned 30-90 days of gestation and postnatal treatments began at approximately 8 weeks of age and continued throughout. Blood samples were taken twice weekly, beginning at approximately 12 weeks of age to time puberty. Two-hour samples after the synchronization with prostaglandin F2α were taken for 120 hours to characterize LH surge dynamics at 7 and 19 months of age. Prenatal T females entered puberty earlier than controls, and all interventions prevented this advancement. Prenatal T reduced the percentage of animals having LH surge, and females that presented LH surge exhibited delayed timing and dampened amplitude of the LH surge. Prenatal androgen antagonist, but not other interventions, restored LH surges without normalizing the timing of the surge. Normalization of pubertal timing with prenatal/postnatal androgen antagonist and insulin sensitizer interventions suggests that pubertal advancement is programmed by androgenic actions of T involving insulin as a mediary. Restoration of LH surges by cotreatment with androgen antagonist supports androgenic programming at the organizational level.

Prenatal care in your second trimester

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000557.htm Prenatal care in your second trimester To use the sharing ... Gregory KD, Ramos DE, Jauniaux ERM. Preconception and prenatal care. In: Gabbe SG, Niebyl JR, Simpson JL, et ...

Prenatal care in your third trimester

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000558.htm Prenatal care in your third trimester To use the sharing ... Gregory KD, Ramos DE, Jauniaux ERM. Preconception and prenatal care. In: Gabbe SG, Niebyl JR, Simpson JL, et ...

Current approaches on non-invasive prenatal diagnosis: Prenatal genomics, transcriptomics, personalized fetal diagnosis

Directory of Open Access Journals (Sweden)

Tuba Günel

2014-12-01

Full Text Available Recent developments in molecular genetics improved our knowledge on fetal genome and physiology. Novel scientific innovations in prenatal diagnosis have accelerated in the last decade changing our vision immensely. Data obtained from fetal genomic studies brought new insights to fetal medicine and by the advances in fetal DNA and RNA sequencing technology novel treatment strategies has evolved. Non-invasive prenatal diagnosis found ground in genetics and the results are widely studied in scientific arena. When Lo and colleges proved fetal genetic material can be extracted from maternal plasma and fetal DNA can be isolated from maternal serum, the gate to many exciting discoveries was open. Microarray technology and advances in sequencing helped fetal diagnosis as well as other areas of medicine. Today it is a very crucial prerequisite for physicians practicing prenatal diagnosis to have a profound knowledge in genetics. Prevailing practical use and application of fetal genomic tests in maternal and fetal medicine mandates obstetricians to update their knowledge in genetics. The purpose of this review is to assist physicians to understand and update their knowledge in fetal genetic testing from maternal blood, individualized prenatal counseling and advancements on the subject by sharing our experiences as İstanbul University Fetal Nucleic Acid Research Group.

Family structure and use of prenatal care

Directory of Open Access Journals (Sweden)

Elisabete Alves

2015-06-01

Full Text Available This cross-sectional study intended to assess the use of prenatal care according to the family structure in a population with free universal access to prenatal care. In 2005-2006, the Portuguese birth cohort was assembled by the recruitment of puerperae at public maternity wards in Porto, Portugal. In the current analysis, 7,211 were included. Data on socio-demographic characteristics, obstetric history, and prenatal care were self-reported. Single mothers were considered as those whose household composition did not include a partner at delivery. Approximately 6% of the puerperae were single mothers. These women were more likely to have an unplanned pregnancy (OR = 6.30; 95%CI: 4.94-8.04, an inadequate prenatal care (OR = 2.30; 95%CI: 1.32-4.02, and to miss the ultrasound and the intake of folic acid supplements during the first trimester of pregnancy (OR = 1.71; 95%CI: 1.30-2.27; and OR = 1.67; 95%CI: 1.32-2.13, respectively. The adequacy and use of prenatal care was less frequent in single mothers. Educational interventions should reinforce the use and early initiation of prenatal care.

Prenatal Stress as a Risk-and an Opportunity-Factor.

Science.gov (United States)

Hartman, Sarah; Freeman, Sara M; Bales, Karen L; Belsky, Jay

2018-04-01

Two separate lines of research indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences. Therefore, prenatal stress may increase sensitivity to the rearing environment. We tested this hypothesis by manipulating prenatal stress and rearing-environment quality, using a cross-fostering paradigm, in prairie voles. Results showed that prenatally stressed voles, as adults, displayed the highest behavioral and physiological reactivity when cross-fostered to low-contact (i.e., low-quality) rearing but the lowest behavioral and physiological reactivity when cross-fostered to high-contact (i.e., high-quality) rearing; non-prenatally stressed voles showed no effect of rearing condition. Additionally, while neither prenatal stress nor rearing condition affected oxytocin receptor binding, prenatally stressed voles cross-fostered to high-contact rearing showed the highest vasopressin-1a receptor binding in the amygdala. Results indicate that prenatal stress induces greater environmental sensitivity, making it both a risk and an opportunity factor.

Prenatal meditation influences infant behaviors.

Science.gov (United States)

Chan, Ka Po

2014-11-01

Meditation is important in facilitating health. Pregnancy health has been shown to have significant consequences for infant behaviors. In view of limited studies on meditation and infant temperament, this study aims to explore the effects of prenatal meditation on these aspects. The conceptual framework was based on the postulation of positive relationships between prenatal meditation and infant health. A randomized control quantitative study was carried out at Obstetric Unit, Queen Elizabeth Hospital in Hong Kong. 64 pregnant Chinese women were recruited for intervention and 59 were for control. Outcome measures were cord blood cortisol, infant salivary cortisol, and Carey Infant Temperament Questionnaire. Cord blood cortisol level of babies was higher in the intervention group (pmeditation can influence fetal health. Carey Infant Temperament Questionnaire showed that the infants of intervention group have better temperament (pmeditation in relation to child health. Present study concludes the positive effects of prenatal meditation on infant behaviors and recommends that pregnancy care providers should provide prenatal meditation to pregnant women. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Access Barriers to Prenatal Care in Emerging Adult Latinas.

Science.gov (United States)

Torres, Rosamar

2016-03-01

Despite efforts to improve access to prenatal care, emerging adult Latinas in the United States continue to enter care late in their pregnancies and/or underutilize these services. Since little is known about emerging adult Latinas and their prenatal care experiences, the purpose of this study was to identify actual and perceived prenatal care barriers in a sample of 54 emerging adult Latinas between 18 and 21 years of age. More than 95% of the sample experienced personal and institutional barriers when attempting to access prenatal care. Results from this study lend support for policy changes for time away from school or work to attend prenatal care and for group prenatal care. © 2016. All rights reserved.

Prenatal ultrasonographic findings of cloacal anomaly

International Nuclear Information System (INIS)

Song, Mi Jin

2002-01-01

To evaluate the ultrasonographic characteristic of a rare malformation comples, Cloacal anomaly on prenatal ultrasonography. From March 1991 to July 2001, eight cases with the persistent cloaca (4 cases in female and 1 case in male) and cloacal exstrophy (3 cases) diagnosed by prenatal ultrasound examination were included, and all of them were pathologically confirmed by autopsy. One radiologist retrospectively analyzed the prenatal sonographic images, including the urinary bladder, kidney, pelvic cyst, abdominal wall defect and amount of amniotic fluid. The ultrasonographic diagnosis was established at 21.8 ± 7.8 weeks of gestation. The prenatal ultrasonographic findings of the persistent cloaca were absent bladder (n=2), distended bladder (n=2) and small thick bladder (n=1). Sonography of the kidney showed normal (n=2), hydronephrosis (n=1), dysplasia (n=1) and unilateral hydronephrosis with absent contralateral kidney (n=1). Four fetuses showed septated pelvic cyst; three fetuses, oligohydramnios. The prenatal ultrasonographic findings of cloacal exstrophy included absent bladder (n=3), normal kidney (n=1), hydronephrosis (n=1) and absent kidney (n=1). All fetuses with cloacal exstrophy had abdominal wall defect while two of them had oligohydramnios. A prenatal diagnosis of persistent cloaca can be confidently made when there is septated pelvic cyst combined oligohydramnios, sediments within the cyst and intraluminal calcifications. Cloacal exstrophy should be included in diagnosis if there is a low abdominal wall defect with absent urinary bladder.

Intermittent Rivers and Biodiversity. Large scale analyses between hydrology and ecology in intermittent rivers

OpenAIRE

Blanchard, Q.

2014-01-01

Intermittent rivers are characterized by a temporary interruption of their flow which can manifest in a variety of ways, as much on a spatial scale as on a temporal one. This particular aspect of intermittent river hydrology gives rise to unique ecosystems, combining both aquatic and terrestrial habitats. Neglected for a long time by scientists and once considered biologically depauperate and ecologically unimportant, these fragile habitats are nowadays acknowledged for their rendered service...

Prenatal Tests

Science.gov (United States)

... tests are considered routine — that is, almost all pregnant women receiving prenatal care get them. They include things like checking urine (pee) levels for protein, sugar, or signs of infection. Other non-routine ...

Prenatal Diagnosis Of Tay-Sachs Disease

Directory of Open Access Journals (Sweden)

Özgür Özyüncü

2010-04-01

CONCLUSION: Tay-Sachs disease can be diagnosed prenatally by measuring hexosaminidase enzyme activity in fetal tissue samples with an acceptable complication rate. Prenatal diagnosis should be offered to families who have affected siblings with Tay-Sachs disease.

Putting intelligent structured intermittent auscultation (ISIA) into practice.

Science.gov (United States)

Maude, Robyn M; Skinner, Joan P; Foureur, Maralyn J

2016-06-01

Fetal monitoring guidelines recommend intermittent auscultation for the monitoring of fetal wellbeing during labour for low-risk women. However, these guidelines are not being translated into practice and low-risk women birthing in institutional maternity units are increasingly exposed to continuous cardiotocographic monitoring, both on admission to hospital and during labour. When continuous fetal monitoring becomes routinised, midwives and obstetricians lose practical skills around intermittent auscultation. To support clinical practice and decision-making around auscultation modality, the intelligent structured intermittent auscultation (ISIA) framework was developed. The purpose of this discussion paper is to describe the application of intelligent structured intermittent auscultation in practice. The intelligent structured intermittent auscultation decision-making framework is a knowledge translation tool that supports the implementation of evidence into practice around the use of intermittent auscultation for fetal heart monitoring for low-risk women during labour. An understanding of the physiology of the materno-utero-placental unit and control of the fetal heart underpin the development of the framework. Intelligent structured intermittent auscultation provides midwives with a robust means of demonstrating their critical thinking and clinical reasoning and supports their understanding of normal physiological birth. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance.

Science.gov (United States)

Baker, Lindsay B; Rollo, Ian; Stein, Kimberly W; Jeukendrup, Asker E

2015-07-14

Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1-2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30-60 g/h in the form of a 6%-7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a game

Medicaid reimbursement, prenatal care and infant health.

Science.gov (United States)

Sonchak, Lyudmyla

2015-12-01

This paper evaluates the impact of state-level Medicaid reimbursement rates for obstetric care on prenatal care utilization across demographic groups. It also uses these rates as an instrumental variable to assess the importance of prenatal care on birth weight. The analysis is conducted using a unique dataset of Medicaid reimbursement rates and 2001-2010 Vital Statistics Natality data. Conditional on county fixed effects, the study finds a modest, but statistically significant positive relationship between Medicaid reimbursement rates and the number of prenatal visits obtained by pregnant women. Additionally, higher rates are associated with an increase in the probability of obtaining adequate care, as well as a reduction in the incidence of going without any prenatal care. However, the effect of an additional prenatal visit on birth weight is virtually zero for black disadvantaged mothers, while an additional visit yields a substantial increase in birth weight of over 20 g for white disadvantaged mothers. Copyright © 2015 Elsevier B.V. All rights reserved.

Prenatal coke: what's behind the smoke? Prenatal cocaine/alcohol exposure and school-age outcomes: the SCHOO-BE experience.

Science.gov (United States)

Delaney-Black, V; Covington, C; Templin, T; Ager, J; Martier, S; Compton, S; Sokol, R

1998-06-21

Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgement of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be

Prenatal Coke: What's Behind the Smoke?: Prenatal Cocaine/Alcohol Exposure and School-Age Outcomes: The SCHOO-BE Experiencea.

Science.gov (United States)

Delaney-Black, Virginia; Covington, Chandice; Templin, Tom; Ager, Joel; Martier, Sue; Compton, Scott; Sokol, Robert

1998-06-01

Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgment of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected Perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be composed

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

DEFF Research Database (Denmark)

Johansen, Sys Stybe; Jornil, Jakob

2009-01-01

), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA or ecstasy). An intra-day precision of 3-6% RSD and an inter-day precision of 3-17% RSD were observed. Trueness was between 96 % and 106% for the target compounds. The limit of detection ranged from 0.07 to 0.14 ng...

Coherent Structures and Intermittency in Plasma Turbulence

International Nuclear Information System (INIS)

Das, Amita; Kaw, Predhiman; Sen, Abhijit

2008-01-01

The paper discusses some fundamental issues related to the phenomenon of intermittency in plasma turbulence with particular reference to experimental observations in fusion devices. Intermittency is typically associated with the presence of coherent structures in turbulence. Since coherent structures can play an important role in governing the transport properties of a system they have received a great deal of attention in fusion research. We review some of the experimental measurements and numerical simulation studies on the presence and formation of coherent structures in plasmas and discuss their relevance to intermittency. Intermittency, as widely discussed in the context of neutral fluid turbulence, implies multiscaling behaviour in contrast to self-similar scaling patterns observed in self organized criticality (SOC) phenomenon. The experimental evidence from plasma turbulence measurements reveal a mixed picture--while some observations support the SOC model description others indicate the presence of multiscaling behaviour. We discuss these results in the light of our present understanding of plasma turbulence and in terms of certain unique aspects of intermittency as revealed by fluid models of plasmas.

The Paradigm of Unity in Prenatal Education and Pedagogy

Directory of Open Access Journals (Sweden)

Kornas-Biela Dorota

2014-07-01

Full Text Available The traditional approach to the relation between parents and their prenatal child presents the child as a fetus, a mainly passive recipient of the mother’s vital biological resources. Contemporary prenatal psychology and pedagogy recognizes this relationship in a quite different perspective: the prenatal child is a member of the family and may be seen as an active member of the wider family as a community, extended to grandparents and other relatives. Between parents and their child in the womb exists a reciprocal relationship at a physiological (hormonal, psychological and spiritual level. The prenatal child communicates with the parents in different ways and reacts to their stimulation (acoustic, tactile, loco-motoric, chemo-receptive, thermo-receptive, and emotional. This dialogue of the parents and their prenatal child enriches each member of the family community. In this sense, the prenatal child is a gift and a challenge for the parents to develop their personality, social competences and spiritual life. The reflections presented in this paper fit the conception of the paradigm of unity applied into the area of prenatal education and prenatal pedagogy as a new pedagogical subdisciline.

Association of Group Prenatal Care With Gestational Weight Gain.

Science.gov (United States)

Kominiarek, Michelle A; Crockett, Amy; Covington-Kolb, Sarah; Simon, Melissa; Grobman, William A

2017-04-01

To compare gestational weight gain among women in group prenatal care with that of women in individual prenatal care. In this retrospective cohort study, women who participated in group prenatal care from 2009 to 2015 and whose body mass indexes (BMIs) and gestational weight gain were recorded were matched with the next two women who had the same payer type, were within 2-kg/m prepregnancy BMI and 2-week gestational age at delivery, and had received individual prenatal care. Bivariate comparisons of demographics and antenatal complications were performed for women in group and individual prenatal care, and weight gain was categorized as "below," "met," or "exceeded" goals according to the 2009 Institute of Medicine guidelines. Logistic regression analysis estimated the association between excessive weight gain and model of care, with adjustment for confounders, stratified by BMI. Women in group prenatal care (n=2,117) were younger and more commonly non-Hispanic black, nulliparous, and without gestational diabetes (P≤.005 for all). Women in group prenatal care more commonly exceeded the weight gain goals (55% compared with 48%, Pprenatal care, compared with individual prenatal care, is associated with excessive gestational weight gain.

The impact of intermittent or sustained carbon dioxide on intermittent hypoxia initiated respiratory plasticity. What is the effect of these combined stimuli on apnea severity?

Science.gov (United States)

Mateika, Jason H; Panza, Gino; Alex, Raichel; El-Chami, Mohamad

2017-10-31

The following review explores the effect that intermittent or sustained hypercapnia coupled to intermittent hypoxia has on respiratory plasticity. The review explores published work which suggests that intermittent hypercapnia leads to long-term depression of respiration when administered in isolation and prevents the initiation of long-term facilitation when administered in combination with intermittent hypoxia. The review also explores the impact that sustained hypercapnia alone and in combination with intermittent hypoxia has on the magnitude of long-term facilitation. After exploring the outcomes linked to intermittent hypoxia/hypercapnia and intermittent hypoxia/sustained hypercapnia the translational relevance of the outcomes as it relates to breathing stability during sleep is addressed. The likelihood that naturally induced cycles of intermittent hypoxia, coupled to oscillations in carbon dioxide that range between hypocapnia and hypercapnia, do not initiate long-term facilitation is addressed. Moreover, the conditions under which intermittent hypoxia/sustained hypercapnia could serve to improve breathing stability and mitigate co-morbidities associated with sleep apnea are considered. Published by Elsevier B.V.

Opportunities and challenges in prenatal diagnosis : towards personalized fetal genetics

NARCIS (Netherlands)

Lichtenbelt, K.D.

2013-01-01

In this thesis we studied the efficacy and utilization of prenatal screening and prenatal diagnosis in the Netherlands and the increasing options for prenatal genetic diagnosis in general. In chapter 1 background information on prenatal screening and diagnosis in pregnancies conceived through

ACOG Committee Opinion No. 731 Summary: Group Prenatal Care.

Science.gov (United States)

2018-03-01

Individual prenatal care is intended to prevent poor perinatal outcomes and provide education to women throughout pregnancy, childbirth, and the postpartum period through a series of one-on-one encounters between a woman and her obstetrician or other obstetric care provider. Concerns regarding increasing health care costs, health care provider availability, dissatisfaction with wait times, and the minimal opportunity for education and support associated with the individual care model have given rise to interest in alternative models of prenatal care. One alternative model, group prenatal care, may be beneficial or preferred for some practice settings and patient populations, although individual prenatal care remains standard practice. Group prenatal care models are designed to improve patient education and include opportunities for social support while maintaining the risk screening and physical assessment of individual prenatal care. Bringing patients with similar needs together for health care encounters increases the time available for the educational component of the encounter, improves efficiency, and reduces repetition. Evidence suggests patients have better prenatal knowledge, feel more ready for labor and delivery, are more satisfied with care in prenatal care groups, and initiate breastfeeding more often. There is no evidence that suggests that group prenatal care causes harm. Individual and group care models warrant additional study with a goal of demonstrating differences in outcomes and identifying populations that benefit most from specific care models.

Intermittent hypoxia increases insulin resistance in genetically obese mice.

Science.gov (United States)

Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

2003-10-01

Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

Prenatal programming of childhood overweight and obesity.

Science.gov (United States)

Huang, Jennifer S; Lee, Tiffany A; Lu, Michael C

2007-09-01

To review the scientific evidence for prenatal programming of childhood overweight and obesity, and discuss its implications for MCH research, practice, and policy. A systematic review of observational studies examining the relationship between prenatal exposures and childhood overweight and obesity was conducted using MOOSE guidelines. The review included literature posted on PubMed and MDConsult and published between January 1975 and December 2005. Prenatal exposures to maternal diabetes, malnutrition, and cigarette smoking were examined, and primary study outcome was childhood overweight or obesity as measured by body mass index (BMI) for children ages 5 to 21. Four of six included studies of prenatal exposure to maternal diabetes found higher prevalence of childhood overweight or obesity among offspring of diabetic mothers, with the highest quality study reporting an odds ratio of adolescent overweight of 1.4 (95% CI 1.0-1.9). The Dutch famine study found that exposure to maternal malnutrition in early, but not late, gestation was associated with increased odds of childhood obesity (OR 1.9, 95% CI 1.5-2.4). All eight included studies of prenatal exposure to maternal smoking showed significantly increased odds of childhood overweight and obesity, with most odds ratios clustering around 1.5 to 2.0. The biological mechanisms mediating these relationships are unknown but may be partially related to programming of insulin, leptin, and glucocorticoid resistance in utero. Our review supports prenatal programming of childhood overweight and obesity. MCH research, practice, and policy need to consider the prenatal period a window of opportunity for obesity prevention.

The Yo-Yo intermittent recovery test

DEFF Research Database (Denmark)

Bangsbo, Jens; Iaia, F. Marcello; Krustrup, Peter

2008-01-01

The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test focuses on the capacity to carry out intermittent exercise leading to a maximal activation of the aerobic system, whereas Yo-Yo IR level 2...

Dynamic characterizers of spatiotemporal intermittency

OpenAIRE

Gupte, Neelima; Jabeen, Zahera

2006-01-01

Systems of coupled sine circle maps show regimes of spatiotemporally intermittent behaviour with associated scaling exponents which belong to the DP class, as well as regimes of spatially intermittent behaviour (with associated regular dynamical behaviour) which do not belong to the DP class. Both types of behaviour are seen along the bifurcation boundaries of the synchronized solutions, and contribute distinct signatures to the dynamical characterizers of the system, viz. the distribution of...

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers.

Science.gov (United States)

Roseman, Leor; Leech, Robert; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

2014-01-01

Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

Directory of Open Access Journals (Sweden)

Leor eRoseman

2014-05-01

Full Text Available Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC between a standard template of different independent components analysis (ICA-derived resting state networks (RSNs under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.

Consumerism in prenatal diagnosis: a challenge for ethical guidelines

Science.gov (United States)

Henn, W.

2000-01-01

The ethical guidelines for prenatal diagnosis proposed by the World Health Organisation (WHO), as well as by national regulations, only refer to paternity and gender of the fetus as unacceptable, disease-unrelated criteria for prenatal selection, as no other such parameters are at hand so far. This perspective is too narrow because research on complex genetic systems such as cognition and ageing is about to provide clinically applicable tests for genetic constituents of potentially desirable properties such as intelligence or longevity which could be misused as parameters for prenatal diagnosis. Moreover, there is an increasing number of prenatally testable genetic traits, such as heritable deafness, which are generally regarded as pathological but desired by some prospective parents and taken into account as parameters for pro-disability selection. To protect prenatal diagnosis from ethically unacceptable genetic consumerism, guidelines must be clarified as soon as possible and updated towards a worldwide restriction of prenatal genetic testing to immediately disease-determining traits. Key Words: Genetics • prenatal diagnosis • ethics • consumerism PMID:11129845

Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance

Directory of Open Access Journals (Sweden)

Lindsay B. Baker

2015-07-01

Full Text Available Intermittent sports (e.g., team sports are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1–2 h. Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1 potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2 the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3 what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports. Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30–60 g/h in the form of a 6%–7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before

Forces and energetics of intermittent swimming

Science.gov (United States)

Floryan, Daniel; Van Buren, Tyler; Smits, Alexander J.

2017-08-01

Experiments are reported on intermittent swimming motions. Water tunnel experiments on a nominally two-dimensional pitching foil show that the mean thrust and power scale linearly with the duty cycle, from a value of 0.2 all the way up to continuous motions, indicating that individual bursts of activity in intermittent motions are independent of each other. This conclusion is corroborated by particle image velocimetry (PIV) flow visualizations, which show that the main vortical structures in the wake do not change with duty cycle. The experimental data also demonstrate that intermittent motions are generally energetically advantageous over continuous motions. When metabolic energy losses are taken into account, this conclusion is maintained for metabolic power fractions less than 1.

Improved prenatal detection of chromosomal anomalies

DEFF Research Database (Denmark)

Frøslev-Friis, Christina; Hjort-Pedersen, Karina; Henriques, Carsten U

2011-01-01

Prenatal screening for karyotype anomalies takes place in most European countries. In Denmark, the screening method was changed in 2005. The aim of this study was to study the trends in prevalence and prenatal detection rates of chromosome anomalies and Down syndrome (DS) over a 22-year period....

Prenatal education for congenital toxoplasmosis.

Science.gov (United States)

Di Mario, Simona; Basevi, Vittorio; Gagliotti, Carlo; Spettoli, Daniela; Gori, Gianfranco; D'Amico, Roberto; Magrini, Nicola

2015-10-23

Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. To assess the effects of prenatal education for preventing congenital toxoplasmosis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials.One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a

Self-Reported Ecstasy/MDMA/“Molly” Use in a Sample of Nightclub and Dance Festival Attendees in New York City

Science.gov (United States)

Palamar, Joseph J.; Acosta, Patricia; Ompad, Danielle C.; Cleland, Charles M.

2016-01-01

Background Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of “Molly,” which is often marketed as pure MDMA. Surveys have generally not included “Molly” in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use—nightlife attendees. Methods We surveyed 679 young adults (age 18–25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. Results Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR=0.37, p = .015). Over a third of ecstasy users (36.8%) reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones [“bath salts”]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. Conclusion A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name). PMID:27661470

Intermittent cranial lung herniation in two dogs.

Science.gov (United States)

Guglielmini, Carlo; De Simone, Antonio; Valbonetti, Luca; Diana, Alessia

2007-01-01

Two aged dogs with chronic obstructive airway disease were evaluated because of intermittent swelling of the ventral cervical region. Radiographs made at expiration and caudal positioning of the forelimbs allowed identification of intermittent cervical lung herniation of the left and right cranial lung lobe in both dogs. Pulmonary hyperinflation, increased expiratory effort, and chronic coughing were considered responsible for the lung herniation. Cervical lung hernia should be included in the differential diagnoses of intermittent cervical swelling in dogs with chronic respiratory disorders associated with increased expiratory effort and chronic coughing.

Comparing CenteringPregnancy® to standard prenatal care plus prenatal education

Science.gov (United States)

2013-01-01

Background There is significant evidence to support the importance of prenatal care in preventing adverse outcomes such as preterm birth and low infant birth weight. Previous studies have indicated that the benefits of prenatal care are not evenly distributed throughout the social strata. In addition, emerging evidence suggests that among particular populations, rates of preterm birth are unchanged or increasing. This suggests that an alternate care model is necessary, one that seeks to addresses some of the myriad of social factors that also contribute to adverse birth outcomes. In previous studies, the group prenatal care model CenteringPregnancy® had been shown to reduce adverse birth outcomes, but to date, no comparison had been made with a model that included prenatal education. This study sought to investigate whether any significant difference remained within the comparison groups when both models accounted for social factors. Methods This analysis was based on survey data collected from a prospective cohort of pregnant women through the All Our Babies Study in Calgary, Alberta. Results At baseline, there were significant differences between the comparison groups in their psychosocial health, with the women in the CenteringPregnancy® group scoring higher levels of depressive symptoms, stress and anxiety. At four months postpartum, the differences between the groups were no longer significant. Conclusions: These results suggest that CenteringPregnancy® can recruit and retain a demographically vulnerable group of women with a constellation of risk factors for poor pregnancy and birth outcomes, including poverty, language barriers and poor mental health. Post program, the rates of stress, anxiety and depression were similar to other women with more social and financial advantage. These findings suggest that CenteringPregnancy® may be a community based care strategy that contributes to improved mental health, knowledge, and behaviours to optimize outcomes

Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases with prenatally diagnosed echogenic kidneys? Prenatal findings in two families with 17q12 microdeletion syndrome and review of the literature.

Science.gov (United States)

Jones, Gabriela E; Mousa, Hatem A; Rowley, Helen; Houtman, Peter; Vasudevan, Pradeep C

2015-12-01

The objective of this study is to report the prenatal ultrasound scan findings in four fetuses from two families postnatally diagnosed with 17q12 microdeletion syndrome on microarray CGH and review the literature. We report two families presenting with prenatally detected hyperechogenic kidneys. In family 1, the mother had three pregnancies complicated by anhydramnios with bilateral hyperechogenic kidneys, hyperechogenic enlarged cystic kidneys, and bilateral hyperechogenic kidneys with polyhydramnios respectively. In family 2, prenatal ultrasound scans detected hyperechogenic kidneys. A pubmed search for all reported cases of 17q12 deletion between 2005 and 2015 was performed. All publications were reviewed, and findings summarised. Fourteen publications were deemed suitable for literature review; there was a diagnosis of 17q12 deletion with documented prenatal findings in 25 cases. Prenatal renal anomalies were reported in 88% of these cases. Anomalies were documented from 15 weeks, and most common presentation was hyperechogenic, muticystic, or enlarged kidneys. Both oligohydramnios and polyhydramnios were seen. Postnatal renal ultrasound scan findings were of muticystic or multicystic dysplastic kidney. There did not appear to be correlation of prenatal presentation and severity of renal disease. Prenatal testing should be offered to all cases of hyperechogenic kidneys, with unknown cause. © 2015 John Wiley & Sons, Ltd.

Playfulness and prenatal alcohol exposure: a comparative study.

Science.gov (United States)

Pearton, Jordan Louise; Ramugondo, Elelwani; Cloete, Lizahn; Cordier, Reinie

2014-08-01

South Africa carries a high burden of alcohol abuse. The effects of maternal alcohol consumption during pregnancy are most pronounced in poor, rural communities. Earlier research suggests that children with prenatal alcohol exposure have poor social behaviour; however, to date, no research has investigated their playfulness. This study investigated the differences in playfulness of children with and without prenatal alcohol exposure. Grade one learners with a positive history of prenatal alcohol exposure (n = 15) and a reference group without a positive history of prenatal alcohol exposure (n = 15) were filmed engaging in free play at their schools. The Test of Playfulness was used to measure playfulness from recordings. Data were subjected to Rasch analysis to calculate interval level measure scores for each participant. The overall measure scores and individual Test of Playfulness social items were subjected to paired samples t-tests to calculate if significant differences existed between the groups. Children with prenatal alcohol exposure had a significantly lower mean overall playfulness score than the reference group (t = -2.51; d.f. = 28; P = 0.02). Children with prenatal alcohol exposure also scored significantly lower than the reference group on 5 of the 12 Test of Playfulness items related to social play. This research suggests that children with prenatal alcohol exposure are more likely to experience poorer overall quality of play, with particular deficits in social play. Considering play is a child's primary occupation, this finding becomes pertinent for occupational therapy practice, particularly in post-apartheid South Africa, where high prenatal alcohol exposure prevalence rates are couched within persistent socio-economic inequalities. © 2014 Occupational Therapy Australia.

Intermittency in the particle production and in the nuclear multifragmentation

International Nuclear Information System (INIS)

Bozek, P.; Ploszajczak, M.

1991-01-01

Intermittency is a manifestation of scale invariance and randomness in physical systems. Intermittency in relativistic heavy-ion collisions and, in particular, the projectile dependence, multiplicity dependence and source-size dependence are discussed in the frame of the model of spatio-temporal intermittency. Moreover, recent theoretical results in intermittency studies of the nuclear multifragmentation are presented. (author) 35 refs., 4 figs., 1 tab

Beneficial effects of intermittent suction and pressure treatment in intermittent claudication

DEFF Research Database (Denmark)

Mehlsen, J; Himmelstrup, H; Himmelstrup, Bodil

1993-01-01

administration. The treatment caused significant increments in the ADP thresholds for platelet aggregation, while the effects on fibrinolysis were uncertain. It is concluded that intermittent suction and pressure treatment offers a new approach for conservative treatment of intermittent claudication....... participated in an open trial investigating the possible effects of the treatment on platelet aggregation and fibrinolysis. Pain-free and maximal walking distances were measured on a treadmill, and systolic blood pressure was measured on the upper limb, the ankle, and the first toe bilaterally. The threshold...... for adenosine diphosphate (ADP)-induced platelet aggregation was tested, and the fibrinolytic activity was estimated from the euglobulin clot lysis time. Active treatment resulted in significant improvements in pain-free and maximal walking distances, whereas no changes could be found during placebo...

Intermittency and random matrices

Science.gov (United States)

Sokoloff, Dmitry; Illarionov, E. A.

2015-08-01

A spectacular phenomenon of intermittency, i.e. a progressive growth of higher statistical moments of a physical field excited by an instability in a random medium, attracted the attention of Zeldovich in the last years of his life. At that time, the mathematical aspects underlying the physical description of this phenomenon were still under development and relations between various findings in the field remained obscure. Contemporary results from the theory of the product of independent random matrices (the Furstenberg theory) allowed the elaboration of the phenomenon of intermittency in a systematic way. We consider applications of the Furstenberg theory to some problems in cosmology and dynamo theory.

Karyotyping or rapid aneuploidy detection in prenatal diagnosis? The different views of users and providers of prenatal care

NARCIS (Netherlands)

Boormans, E. M. A.; Birnie, E.; Bilardo, C. M.; Oepkes, D.; Bonsel, G. J.; van Lith, J. M. M.

2009-01-01

Developments in prenatal diagnosis raise the question which test strategy should be implemented. However, preferences of women and caregivers are underexposed. This study investigates what kind of prenatal test pregnant women and caregivers prefer and if differences between the groups exist, using

Intermittent behavior of the logistic system

Science.gov (United States)

Mayer-Kress, G.; Haken, H.

1981-03-01

In the discrete logistic model a transition to chaotic behavior via intermittency occurs in a neighborhood of periodic bands. Intermittent behavior is also induced if a stable periodic orbit is perturbed by low-level external noise, whereas alterations due to computer digitalisation produce remarkable periodicities. We compare our numerical results with the predictions of Pomeau and Manneville for the Lorenz system.

The accuracy of 2D ultrasound prenatal sex determination ...

African Journals Online (AJOL)

Most of the women were happy even when the sex differed from that which they desired. Conclusion: Prenatal sonographic sex determination has a high sensitivity index. Consequently we advocate its use prior to more invasive sex tests. Keywords: Accuracy, gender determination, prenatal gender, prenatal sex, sex ...

Intermittent hydronephrosis

International Nuclear Information System (INIS)

Knop, J.; Vogel, H.; Hupe, W.

1981-01-01

An intermittent hydronephrosis was observed in a 40-year old patient. This disease pattern is due to an incongruity between the formation of urine and the transport capacity in the ureteropelvic junction. The latent impediment of flow becomes manifest with increased urine secretion. Irreversible renal damage can be the result of the repeatedly occurring hydronephrotic crises. (orig.) [de

Navigating intimacy with ecstasy: The emotional, \\ud spatial and boundaried dynamics of couples’ MDMA \\ud experiences

OpenAIRE

Anderson, Katie

2017-01-01

MDMA (3,4-methylenedioxy-methamphetamine or ‘ecstasy’) is well-known for its\\ud empathic and sociable effects (Bogt, Engels, Hibbel & Van Wel, 2002). Indeed, there \\ud is a body of work that discusses the role the drug plays in social bonding (Beck &\\ud Rosenbaum, 1998; Duff, 2008; Farrugia, 2015; Hinchliff, 2001; Solowij, Hall & Lee, \\ud 1992). However, there has been extremely limited research looking at MDMA’s \\ud impact specifically on romantic relationships (Vervaeke & Korf, 2006). Hence...

The Motivation-Facilitation Theory of Prenatal Care Access.

Science.gov (United States)

Phillippi, Julia C; Roman, Marian W

2013-01-01

Despite the availability of services, accessing health care remains a problem in the United States and other developed countries. Prenatal care has the potential to improve perinatal outcomes and decrease health disparities, yet many women struggle with access to care. Current theories addressing access to prenatal care focus on barriers, although such knowledge is minimally useful for clinicians. We propose a middle-range theory, the motivation-facilitation theory of prenatal care access, which condenses the prenatal care access process into 2 interacting components: motivation and facilitation. Maternal motivation is the mother's desire to begin and maintain care. Facilitation represents the goal of the clinic to create easy, open access to person-centered beneficial care. This simple model directs the focus of research and change to the interface of the woman and the clinic and encourages practice-level interventions that facilitate women entering and maintaining prenatal care. © 2013 by the American College of Nurse‐Midwives.

Adequacy of Prenatal Care and Gestational Weight Gain.

Science.gov (United States)

Yeo, SeonAe; Crandell, Jamie L; Jones-Vessey, Kathleen

2016-02-01

The goal of prenatal care is to maximize health outcomes for a woman and her fetus. We examined how prenatal care is associated with meeting the 2009 Institute of Medicine (IOM) guidelines for gestational weight gain. The study used deidentified birth certificate data supplied by the North Carolina State Center for Health Statistics. The sample included 197,354 women (≥18 years) who delivered singleton full-term infants in 2011 and 2012. A generalized multinomial model was used to identify how adequate prenatal care was associated with the odds of gaining excessive or insufficient weight during pregnancy according to the 2009 IOM guidelines. The model adjusted for prepregnancy body size, sociodemographic factors, and birth weight. A total of 197,354 women (≥18 years) delivered singleton full-term infants. The odds ratio (OR) for excessive weight gain was 2.44 (95% CI 2.37-2.50) in overweight and 2.33 (95% CI 2.27-2.40) in obese women compared with normal weight women. The OR for insufficient weight gain was 1.15 (95% CI 1.09-1.22) for underweight and 1.34 (95% CI 1.30-1.39) for obese women compared with normal weight women. Prenatal care at the inadequate or intermediate levels was associated with insufficient weight gain (OR: 1.32, 95% CI 1.27-1.38; OR: 1.15, 95% CI 1.09-1.21, respectively) compared with adequate prenatal care. Women with inadequate care were less likely to gain excessive weight (OR: 0.88, 95% CI 0.86-0.91). Whereas prenatal care was effective for preventing insufficient weight gain regardless of prepregnancy body size, educational background, and racial/ethnic group, there were no indications that adequate prenatal care was associated with reduced risk for excessive gestational weight gain. Further research is needed to improve prenatal care programs for preventing excess weight gain.

The comparative effects of group prenatal care on psychosocial outcomes.

Science.gov (United States)

Heberlein, Emily C; Picklesimer, Amy H; Billings, Deborah L; Covington-Kolb, Sarah; Farber, Naomi; Frongillo, Edward A

2016-04-01

To compare the psychosocial outcomes of the CenteringPregnancy (CP) model of group prenatal care to individual prenatal care, we conducted a prospective cohort study of women who chose CP group (N = 124) or individual prenatal care (N = 124). Study participants completed the first survey at study recruitment (mean gestational age 12.5 weeks), with 89% completing the second survey (mean gestational age 32.7 weeks) and 84% completing the third survey (6 weeks' postpartum). Multiple linear regression models compared changes by prenatal care model in pregnancy-specific distress, prenatal planning-preparation and avoidance coping, perceived stress, affect and depressive symptoms, pregnancy-related empowerment, and postpartum maternal-infant attachment and maternal functioning. Using intention-to-treat models, group prenatal care participants demonstrated a 3.2 point greater increase (p prenatal planning-preparation coping strategies. While group participants did not demonstrate significantly greater positive outcomes in other measures, women who were at greater psychosocial risk benefitted from participation in group prenatal care. Among women reporting inadequate social support in early pregnancy, group participants demonstrated a 2.9 point greater decrease (p = 0.03) in pregnancy-specific distress in late pregnancy and 5.6 point higher mean maternal functioning scores postpartum (p = 0.03). Among women with high pregnancy-specific distress in early pregnancy, group participants had an 8.3 point greater increase (p prenatal planning-preparation coping strategies in late pregnancy and a 4.9 point greater decrease (p = 0.02) in postpartum depressive symptom scores. This study provides further evidence that group prenatal care positively impacts the psychosocial well-being of women with greater stress or lower personal coping resources. Large randomized studies are needed to establish conclusively the biological and psychosocial benefits of group

Prenatal stress alters amygdala functional connectivity in preterm neonates.

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Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

2016-01-01

Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

Prenatal exposure to anticonvulsants and psychosexual development

NARCIS (Netherlands)

Dessens, A. B.; Cohen-Kettenis, P. T.; Mellenbergh, G. J.; vd Poll, N.; Koppe, J. G.; Boer, K.

1999-01-01

Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in

Informed Consent - Attitudes, knowledge and information concerning prenatal examination

DEFF Research Database (Denmark)

Dahl, Katja; Kesmodel, Ulrik; Hvidman, Lone

estimates is low and possible consequences if the test reveals a problem is seldom considered beforehand. A woman's attitude to prenatal examinations is found decisive for up-take of prenatal tests, with no association between a woman's attitude towards prenatal examinations and her knowledge of those tests....... Most women consider their doctor an important source of information, and state that information has influenced their decision.      Conclusions: Pregnant women favor prenatal examinations, but participation does not seem to be based on an informed consent....

Prenatal and postnatal cocaine exposure predict teen cocaine use

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Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

2015-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

Characterization of intermittency in zooplankton behaviour in turbulence.

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Michalec, François-Gaël; Schmitt, François G; Souissi, Sami; Holzner, Markus

2015-10-01

We consider Lagrangian velocity differences of zooplankters swimming in still water and in turbulence. Using cumulants, we quantify the intermittency properties of their motion recorded using three-dimensional particle tracking velocimetry. Copepods swimming in still water display an intermittent behaviour characterized by a high probability of small velocity increments, and by stretched exponential tails. Low values arise from their steady cruising behaviour while heavy tails result from frequent relocation jumps. In turbulence, we show that at short time scales, the intermittency signature of active copepods clearly differs from that of the underlying flow, and reflects the frequent relocation jumps displayed by these small animals. Despite these differences, we show that copepods swimming in still and turbulent flow belong to the same intermittency class that can be modelled by a log-stable model with non-analytical cumulant generating function. Intermittency in swimming behaviour and relocation jumps may enable copepods to display oriented, collective motion under strong hydrodynamic conditions and thus, may contribute to the formation of zooplankton patches in energetic environments.

Prenatal maternal stress in relation to the effects of prenatal lead exposure on toddler cognitive development.

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Zhou, Leilei; Xu, Jian; Zhang, Jinsong; Yan, Chonghuai; Lin, Yanfen; Jia, Yinan; Hu, Wenjing

2017-03-01

To evaluate the effects of maternal lead exposure during pregnancy on toddler cognitive development and the potential effect modification by maternal stress. We conducted a prospective birth-cohort study in Shanghai from 2010 to 2012 and investigated 225 mother-infant pairs. The mothers were recruited in mid-to-late pregnancy and children were followed up until 24-36 months old. A self-administered Symptom Checklist-90-Revised Scale (SCL-90-R) was used to assess maternal emotional stress during pregnancy. Maternal whole blood lead levels were measured during gestational weeks 28-36. The toddlers' cognitive levels were assessed using the Gesell Development Scale. Multiple linear regression models were established to explore the main effects of prenatal lead exposure on toddlers' cognitive abilities and the modifying effects of maternal stress. Covariate information was collected through interviews, questionnaires and medical records. The mean maternal blood lead concentration was 3.30 (95%CI: 3.05, 3.57) μg/dL. After adjusting for relevant confounders, no significant associations of maternal blood lead concentrations with toddlers' cognitive levels were observed in all five domains of the Gesell scale (P>0.05). However, the interaction between prenatal maternal blood lead and stress was significant in the domains of adaptive behavior, language and social behavior. When stratified by maternal stress levels, compared with non-significant associations (P>0.05) among low (P1-P75) prenatal stress group, adverse associations between maternal blood lead concentrations (log10-transformed) and toddlers' cognitive levels were observed among high (P75-P100) prenatal stress group in the domains of language (β=-33.82, 95%CI: -60.04, -7.59), social behavior (β=-41.00, 95%CI: -63.11, -18.89) and adaptive behavior (β=-17.93, 95%CI: -35.83, -0.03). Prenatal maternal stress may exacerbate the deleterious effects of prenatal exposure to lead on toddler cognitive development

Unsteady propulsion by an intermittent swimming gait

Science.gov (United States)

Akoz, Emre; Moored, Keith W.

2018-01-01

Inviscid computational results are presented on a self-propelled swimmer modeled as a virtual body combined with a two-dimensional hydrofoil pitching intermittently about its leading edge. Lighthill (1971) originally proposed that this burst-and-coast behavior can save fish energy during swimming by taking advantage of the viscous Bone-Lighthill boundary layer thinning mechanism. Here, an additional inviscid Garrick mechanism is discovered that allows swimmers to control the ratio of their added mass thrust-producing forces to their circulatory drag-inducing forces by decreasing their duty cycle, DC, of locomotion. This mechanism can save intermittent swimmers as much as 60% of the energy it takes to swim continuously at the same speed. The inviscid energy savings are shown to increase with increasing amplitude of motion, increase with decreasing Lighthill number, Li, and switch to an energetic cost above continuous swimming for sufficiently low DC. Intermittent swimmers are observed to shed four vortices per cycle that form into groups that are self-similar with the DC. In addition, previous thrust and power scaling laws of continuous self-propelled swimming are further generalized to include intermittent swimming. The key is that by averaging the thrust and power coefficients over only the bursting period then the intermittent problem can be transformed into a continuous one. Furthermore, the intermittent thrust and power scaling relations are extended to predict the mean speed and cost of transport of swimmers. By tuning a few coefficients with a handful of simulations these self-propelled relations can become predictive. In the current study, the mean speed and cost of transport are predicted to within 3% and 18% of their full-scale values by using these relations.

Prenatal and adult androgen activities in alcohol dependence.

Science.gov (United States)

Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

2017-07-01

Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prenatal Influences on Human Sexual Orientation: Expectations versus Data.

Science.gov (United States)

Breedlove, S Marc

2017-08-01

In non-human vertebrate species, sexual differentiation of the brain is primarily driven by androgens such as testosterone organizing the brains of males in a masculine fashion early in life, while the lower levels of androgen in developing females organize their brains in a feminine fashion. These principles may be relevant to the development of sexual orientation in humans, because retrospective markers of prenatal androgen exposure, namely digit ratios and otoacoustic emissions, indicate that lesbians, on average, were exposed to greater prenatal androgen than were straight women. Thus, the even greater levels of prenatal androgen exposure experienced by fetal males may explain why the vast majority of them grow up to be attracted to women. However, the same markers indicate no significant differences between gay and straight men in terms of average prenatal androgen exposure, so the variance in orientation in men cannot be accounted for by variance in prenatal androgen exposure, but may be due to variance in response to prenatal androgens. These data contradict several popular notions about human sexual orientation. Sexual orientation in women is said to be fluid, sometimes implying that only social influences in adulthood are at work, yet the data indicate prenatal influences matter as well. Gay men are widely perceived as under-masculinized, yet the data indicate they are exposed to as much prenatal androgen as straight men. There is growing sentiment to reject "binary" conceptions of human sexual orientations, to emphasize instead a spectrum of orientations. Yet the data indicate that human sexual orientation is sufficiently polarized that groups of lesbians, on average, show evidence of greater prenatal androgen exposure than groups of straight women, while groups of gay men have, on average, a greater proportion of brothers among their older siblings than do straight men.

[Social factors associated with use of prenatal care in Ecuador].

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